levoleucovorin and Nausea

FOLFIRINOX has been one of the first-line options for advanced pancreatic cancer, even though it induces significant adverse effects. Several institutions have begun using modified FOLFIRINOX to decrease its side effects and increase its tolerability. We systematically investigated the outcome from patients who initially received modified FOLFIRINOX as a chemotherapy regimen for advanced pancreatic cancer. We used the random-model generic inverse variance method to analyse the binary data with 95% confidence intervals (CIs). Eleven studies were included in the meta-analysis with 563 total patients. The 6-month and 1-year overall survival (OS) rates of locally advanced pancreatic cancer (LAPC) were 90.9% and 76.2%. The 6-month and 1-year progression-free survival (PFS) rates of LAPC were 81.5% and 48.5%. The 6-month and 1-year OS rates of metastatic pancreatic cancer (MPC) were 79.7% and 47.6%. The 6-month and 1-year PFS rates of MPC were 56.3% and 20.6%. The following rates were also calculated: complete response rate (CR): 2.9%; partial response rate (PR): 35.9%; stable disease rate (SD): 41.2%; overall response rate (OR): 34.6%; disease control rate (DCR): 76.7%; progressive disease: 23.1%; and grade III/IV adverse events (AEs): neutropenia 23.1%, febrile neutropenia 4.8%, thrombocytopenia 4.8%, anaemia 5.7%, fatigue 11.5%, nausea 9.1%, diarrhoea 10.1%, vomiting 5.7%, neuropathy 3.8%, and increased ALT 5.7%. In conclusion, modified FOLFIRINOX could provide comparative survival benefits with fewer adverse events compared to the conventional dosage.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Fatigue; Fluorouracil; Humans; Irinotecan; Leucovorin; Nausea; Neutropenia; Oxaliplatin; Pancreas; Pancreatic Neoplasms; Survival Analysis; Thrombocytopenia; Treatment Outcome

To evaluate the efficiency and safety profile of raltitrexed-based chemotherapy in the treatment of advanced colorectal cancer.. An electronic search was undertaken to identify randomized controlled trials comparing raltitrexed-based regimen to 5-fluorouracil-based regimen in patients with advanced colorectal cancer. The outcomes included overall survival, overall response rate and toxicities.. This meta-analysis included 11 studies with 4622 patients. Overall, there were no significant differences between the two regimens in terms of overall survival (HR=1.06, 95% CI: 0.96-1.17, P=0.23) or overall response rate (RR=1.09, 95% CI: 0.86-1.38, P=0.47). In subgroup analysis, patients in raltitrexed/oxaliplatin group had significantly higher partial response (RR=1.53, 95% CI: 1.17-2.00, P=0.002), overall response rate (RR=1.42, 95% CI: 1.10-1.82, P=0.006), disease control rate (RR=1.16, 95% CI: 1.04-1.29, P=0.009) and lower progressive disease (RR=0.61, 95% CI: 0.45-0.84, P=0.002) when compared to 5-fluorouracil/leucovorin/oxaliplatin group. Occurrence of severe anemia (RR=2.23, 95% CI: 1.38-3.59, P=0.0001), asthenia (RR=2.29, 95% CI: 1.36-3.84, P=0.002), hepatic disorders (RR=7.51, 95% CI: 1.30-43.56, P=0.02), and nausea/vomit (RR=1.70, 95% CI: 1.03-2.81, P=0.04) were significantly higher with the raltitrexed arm treatment, while frequencies of grade 3/4 alopecia (RR=0.36, 95% CI: 0.26-0.50, P<0.00001) and stomatitis/mucositis (RR=0.14, 95% CI: 0.07-0.31, P<0.00001) were increased in the 5-fluorouracil group.. Raltitrexed-based chemotherapy regimen leads to an equivalent overall survival and response rates with acceptable toxicities compared to traditional 5-fluorouracil-based regimen in patients with advanced colorectal cancer. Raltitrexed can be a treatment option for these patients when 5-fluorouracil-based regimens are not tolerated or inappropriate.

Topics: Alopecia; Anemia; Antineoplastic Combined Chemotherapy Protocols; Asthenia; Chemical and Drug Induced Liver Injury; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Mucositis; Nausea; Organoplatinum Compounds; Oxaliplatin; Quinazolines; Randomized Controlled Trials as Topic; Stomatitis; Thiophenes; Vomiting

Methotrexate (MTX) is a disease modifying antirheumatic drug (DMARD) used as a first line agent for treating rheumatoid arthritis (RA). Pharmacologically, it is classified as an antimetabolite due to its antagonistic effect on folic acid metabolism. Many patients treated with MTX experience mucosal, gastrointestinal, hepatic or haematologic side effects. Supplementation with folic or folinic acid during treatment with MTX may ameliorate these side effects.. To identify trials of supplementation with folic acid or folinic acid during MTX therapy for rheumatoid arthritis and to assess the benefits and harms of folic acid and folinic acid (a) in reducing the mucosal, gastrointestinal (GI), hepatic and haematologic side effects of MTX, and (b) whether or not folic or folinic acid supplementation has any effect on MTX benefit.. We originally performed MEDLINE searches, from January 1966 to June 1999. During the update of this review, we searched additional databases and used a sensitive search strategy designed to retrieve all trials on folic acid or folinic acid for rheumatoid arthritis from 1999 up to 2 March 2012.. We selected all double-blind, randomised, placebo-controlled clinical trials (RCTs) in which adult patients with rheumatoid arthritis were treated with MTX (at a dose equal to or less than 25 mg/week) concurrently with folate supplementation. In this update of the review we only included trials using 'low dose' folic or folinic acid (a starting dose of ≤ 7 mg weekly).. Data were extracted from the trials, and the trials were independently assessed for risk of bias using a predetermined set of criteria.. Six trials with 624 patients were eligible for inclusion. Most studies had low or unclear risk of bias for key domains. The quality of the evidence was rated as 'moderate' for each outcome as assessed by GRADE, with the exception of haematologic side effects which were rated as 'low'. There was no significant heterogeneity between trials, including where folic acid and folinic acid studies were pooled.For patients supplemented with any form of exogenous folate (either folic or folinic acid) whilst on MTX therapy for rheumatoid arthritis, a 26% relative (9% absolute) risk reduction was seen for the incidence of GI side effects such as nausea, vomiting or abdominal pain (RR 0.74, 95% CI 0.59 to 0.92; P = 0.008). Folic and folinic acid also appear to be protective against abnormal serum transaminase elevation caused by MTX, with a 76.9% relative (16% absolute) risk reduction (RR 0.23, 95% CI 0.15 to 0.34; P < 0.00001), as well as reducing patient withdrawal from MTX for any reason (60.8% relative (15.2% absolute) risk reduction, RR 0.39, 95% CI 0.28 to 0.53; P < 0.00001).We analysed the effect of folic or folinic acid on the incidence of stomatitis / mouth sores, and whilst showing a trend towards reduction in risk, the results were not statistically significant (RR 0.72, 95% CI 0.49 to 1.06)It was not possible to draw meaningful conclusions on the effect of folic or folinic acid on haematologic side effects of methotrexate due to small numbers of events and poor reporting of this outcome in included trials.It does not appear that supplementation with either folic or folinic acid has a statistically significant effect on the efficacy of MTX in treating RA (as measured by RA disease activity parameters such as tender and swollen joint counts, or physician's global assessment scores).. The results support a protective effect of supplementation with either folic or folinic acid for patients with rheumatoid arthritis during treatment with MTX.There was a significant reduction shown in the incidence of GI side effects, hepatic dysfunction (asmeasured by elevated serum transaminase levels) as well as a significant reduction in discontinuation of MTX treatment for any reason. A trend towards a reduction in stomatitis was demonstrated however this did not reach statistical significance.This updated review with its focus on lower doses of folic acid and folinic acid and updated assessment of risk of bias aimed to give a more precise and more clinically relevant estimate of the benefit of folate supplementation for patients with rheumatoid arthritis receiving methotrexate.

Topics: Abdominal Pain; Adult; Antirheumatic Agents; Arthritis, Rheumatoid; Folic Acid; Folic Acid Antagonists; Gastrointestinal Diseases; Hematologic Diseases; Humans; Leucovorin; Methotrexate; Nausea; Vomiting

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Duodenal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Multiple Organ Failure; Nausea; Organoplatinum Compounds; Severity of Illness Index; Vomiting

Topics: Adenocarcinoma; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Dexamethasone; Diabetes Mellitus, Type 2; Disease Management; Drug Resistance; Drug Therapy, Combination; Exenatide; Fluorouracil; Humans; Hyperglycemia; Hyperglycemic Hyperosmolar Nonketotic Coma; Hypoglycemic Agents; Insulin; Leucovorin; Male; Malnutrition; Metformin; Middle Aged; Nausea; Organoplatinum Compounds; Oxaliplatin; Palliative Care; Pancreatectomy; Pancreatic Neoplasms; Peptides; Sulfonylurea Compounds; Venoms

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Camptothecin; Clinical Trials as Topic; Colorectal Neoplasms; Diarrhea; Fluorouracil; Humans; Irinotecan; Leucovorin; Leukopenia; Nausea; Stomatitis; Thrombocytopenia; Vomiting

The prevention of chemotherapy-induced nausea and vomiting has an important role in the overall management of cancer treatment.. To evaluate whether adding aprepitant to palonosetron and dexamethasone can further prevent the incidence and severity of nausea and vomiting caused by FOLFIRI (fluorouracil, leucovorin, and irinotecan) or FOLFOX (fluorouracil, leucovorin, and oxaliplatin) chemotherapy regimens among women with gastrointestinal cancer at higher risk.. This phase 3, double-blind, placebo-controlled randomized clinical trial recruited young women (age ≤50 years) who drank little or no alcohol and had gastrointestinal cancer for which they received FOLFOX or FOLFIRI chemotherapy. A total of 248 women were enrolled and assigned in the ratio 1:1 to intervention and control groups from August 4, 2015, to March 31, 2020. Intention-to-treat analysis was used to evaluate patient baseline characteristics and efficacy. The analysis was conducted on October 30, 2020.. Patients were randomly assigned to the aprepitant group (aprepitant, 125 mg, orally 60 minutes before initiation of chemotherapy on day 1 and 80 mg orally each morning of days 2 and 3; palonosetron, 0.25 mg, intravenously; and dexamethasone, 6 mg, orally 30 minutes before chemotherapy initiation on day 1) or the placebo group (placebo, 125 mg, orally 60 minutes before initiation of chemotherapy on day 1 and 80 mg orally on each morning of days 2 and 3; palonosetron, 0.25 mg, intravenously; and dexamethasone, 12 mg, orally 30 minutes before chemotherapy initiation on day 1).. The primary end point was the complete response (CR) rate, defined as the proportion of patients without emesis episodes or rescue medication use during the overall phase of the first cycle. Other efficacy indicators, such as no vomiting and no nausea, were measured as the secondary and exploratory end points.. A total of 248 women from 4 clinical centers in China entered this study, and 243 patients (aprepitant regimen, 125 patients [51.4%]; placebo regimen, 118 patients [48.5%]) were evaluable for efficacy and safety; mean (SD) age of the total population was 40.1 (7.3) years. The CR rate was significantly higher in the aprepitant group vs the control group overall (107 [87.0%] vs 80 [66.7%]; P < .001) and in the acute (114 [92.7%] vs 91 [75.8%]; P = .001) and delayed (109 [88.6%] vs 84 [70.0%]; P = .001) phases of the trial. The incidence of adverse events was similar between the 2 groups (100 [80.0%] vs 96 [81.3%]; P = .79), and no grade 3 or 4 aprepitant treatment-related adverse events were observed. Multivariable analysis revealed that aprepitant use was the only independent factor associated with CR during the overall phase.. The combination of aprepitant with palonosetron and dexamethasone provided increased antiemetic efficacy in the FOLFOX or FOLFIRI chemotherapy regimen and was well tolerated by younger women with gastrointestinal cancer who have a history of little or no alcohol consumption.. ClinicalTrials.gov Identifier: NCT03674294.

Topics: Adult; Antiemetics; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Camptothecin; China; Double-Blind Method; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Nausea; Organoplatinum Compounds; Stomach Neoplasms; Vomiting

Irinotecan, a topoisomerase inhibitor, is a common cytotoxic agent prescribed for metastatic colorectal cancer (mCRC) patients. Diarrhea is the most common adverse event (AE). The underlying mechanism of irinotecan-induced diarrhea is intestinal mucosal damage caused by SN-38 (active metabolite of irinotecan) hydrolyzed from SN-38G (inactive metabolite) by bacterial -glucuronidase (G). According to an animal study, silymarin reduces the activity of bacterial G without impairing antitumor efficacy. We conducted a prospective open-label pilot study to evaluate the effect of silymarin as supplementation in reducing toxicities of mCRC patients undergoing irinotecan-based chemotherapy. We enrolled and randomized 70 mCRC patients receiving first-line FOLFIRI (5-fluorouracil/leucovorin/irinotecan) plus bevacizumab. In each treatment cycle, the study group was administered silymarin capsules (150 mg) three times daily for 7 days. The study group experienced less AEs in diarrhea (5.7% vs. 14.6%,

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Diarrhea; Dietary Supplements; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Nausea; Pilot Projects; Prospective Studies; Protective Agents; Silymarin; Treatment Outcome; Young Adult

Biweekly schedule of XELOX-2 (capecitabine plus oxaliplatin) showed interesting results in first-line therapy of patients with metastatic colorectal cancer (mCRC). Bevacizumab plus FOLFOX-4 (oxaliplatin, folinic acid, and infusional 5-fluorouracil) is among standard first-line treatment options in this setting. We performed a phase II randomized trial in order to evaluate the activity of bevacizumab plus either FOLFOX-4 or XELOX-2 in first-line therapy of patients with mCRC.. Patients with mCRC were randomized, in a 1:2 ratio, to first-line bevacizumab plus either FOLFOX-4 (Arm A), as calibration arm, or XELOX-2 (Arm B), up to 12 cycles. Patients without progression were further randomized to maintenance bevacizumab alone or with the same induction fluoropyrimidine. The primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival, overall survival, and toxicity. The study design was formally non-comparative, but exploratory comparison was performed.. Forty-five patients were randomized in arm A and 87 in arm B with an ORR of 55.6% versus 48.3% (P = .43), respectively. After a median follow-up of 47.2 months, progression-free survival was 10.0 versus 9.9 months (hazard ratio, 0.96; 95% confidence interval, 0.65-1.41; P = .84) and overall survival was 29.8 versus 25.0 months (hazard ratio, 1.21; 95% confidence interval, 0.77-1.92; P = .41), respectively. The main grade 3 to 4 toxicities (% A/B) were: neutropenia 15/3 and nausea 9/5.. This exploratory analysis showed that biweekly XELOX-2 plus bevacizumab has a comparable ORR with FOLFOX-4 plus bevacizumab in patients with mCRC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Capecitabine; Colorectal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Nausea; Neutropenia; Organoplatinum Compounds; Oxaloacetates; Progression-Free Survival; Severity of Illness Index

Topics: Abdominal Pain; Acute Disease; Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Data Analysis; Diarrhea; Fluorouracil; Humans; Irinotecan; Leucovorin; Middle Aged; Nausea; Organs at Risk; Oxaliplatin; Pancreatic Neoplasms; Prospective Studies; Radiation Dosage; Radiosurgery; Time Factors

Standard first-line regimens for patients with metastatic gastroesophageal adenocarcinomas have an approximate 40% objective response rate (ORR). The combination of leucovorin, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) has been efficacious as first-line therapy for other gastrointestinal cancers, such as pancreatic and colon cancers.. To evaluate the clinical activity and safety of FOLFIRINOX as first-line treatment for patients with advanced gastroesophageal adenocarcinoma.. This is an open-label, single-arm phase 2 study of first-line FOLFIRINOX in patients with advanced gastroesophageal adenocarcinoma. Estimated sample size included 41 patients with ERBB2-negative disease with 90% power to detect an ORR of 60% or greater with α of .10. No enrollment goal was planned for ERBB2-positive patients, but they were allowed to receive trastuzumab in combination with FOLFIRINOX.. Starting doses were fluorouracil, 400 mg/m2 bolus, followed by 2400 mg/m2 over 46 hours; leucovorin, 400 mg/m2; irinotecan, 180 mg/m2; and oxaliplatin, 85 mg/m2. Trastuzumab was administered as a 6 mg/kg loading dose, followed by 4 mg/kg every 14 days in patients with ERBB2-positive disease.. The primary end point was ORR by the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points included safety profile, progression-free survival (PFS), overall survival (OS), and duration of response.. From November 2013 to May 2018, 67 patients were enrolled (median [range] age, 59.0 [34-78] years; including 56 [84%] men), and 26 of 67 (39%) had ERBB2-positive disease. Median follow-up was 17.4 months. The ORR was 61%(95% CI, 44.5%-75.8%) (25 of 41) in the ERBB2-negative group and 85% (95% CI, 65.1%-95.6%) (22 of 26) in the ERBB2-positive group, including 1 patient with complete response. For ERBB2-negative patients, median PFS was 8.4 months and median OS was 15.5 months; for ERBB2-positive patients, median PFS was 13.8 months and median OS was 19.6 months. Fifty-six patients (84%) had dose modifications or treatment delays. The most common toxic effects were neutropenia (91%, n = 61), diarrhea (63%, n = 42), peripheral sensory neuropathy (61%, n = 41), and nausea (48%, n = 32), with no unexpected toxic effects.. The FOLFIRINOX regimen with or without trastuzumab was associated with improved ORR and PFS in patients with advanced gastroesophageal adenocarcinoma in the first-line setting. This regimen may be a reasonable therapeutic option for patients with preserved performance status.. ClinicalTrials.gov Identifier: NCT01928290.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Esophageal Neoplasms; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Nausea; Neutropenia; Oxaliplatin; Peripheral Nervous System Diseases; Stomach Neoplasms; Trastuzumab; Treatment Outcome

The phase III TRIBE and TRIBE2 studies randomized metastatic colorectal cancer patients to first-line FOLFOXIRI/bevacizumab or a doublet (FOLFIRI or FOLFOX)/bevacizumab. The studies demonstrated a significant benefit from the triplet at the price of an increased incidence of chemotherapy-related adverse events (AEs). In both trials, males and females aged between 18 and 70 years with ECOG PS ≤2 and between 71 and 75 years with ECOG PS = 0 were eligible. We investigated the effect of FOLFOXIRI/bevacizumab versus doublets/bevacizumab according to age and gender.. Subgroup analyses according to age (<70 versus 70-75 years) and gender were carried out for overall response rate (ORR), progression-free survival (PFS), and AE rates.. Of 1187 patients, 1005 (85%) were aged <70 years and 182 (15%) 70-75 years; 693 (58%) were males and 494 (42%) females. There was no evidence of interaction between age or gender and the benefit provided by the intensification of the upfront chemotherapy in terms of ORR and PFS, or the increased risk of experiencing G3/4 AEs. Elderly patients and females experienced higher rates of overall G3/4 AEs (73% versus 60%, P < 0.01 and 69% versus 57%, P < 0.01, respectively). Notably, in the FOLFOXIRI/bevacizumab subgroup, G3/4 diarrhea and febrile neutropenia occurred in 27% and 16% of elderly patients, respectively, while females reported high incidences of any grade nausea (67%) and vomiting (50%).. The improvements in terms of ORR and PFS of FOLFOXIRI/bevacizumab versus doublets/bevacizumab are independent of gender and age, with a similar relative increase in AEs among elderly patients and females. Initial dose reductions and possibly primary G-CSF prophylaxis should be recommended for patients between 70 and 75 years old treated with FOLFOXIRI/bevacizumab, and a careful management of antiemetic prophylaxis should be considered among females.

Topics: Age Factors; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Nausea; Neoplasm Metastasis; Organoplatinum Compounds; Progression-Free Survival; Sex Characteristics; Treatment Outcome; Vomiting

The objectives of this study were to evaluate the safety profile of aflibercept and health-related quality of life (HRQL) in patients with metastatic colorectal cancer (mCRC) provided with aflibercept access before marketing authorization.. Patients received aflibercept followed by FOLFIRI (fluorouracil, leucovorin, irinotecan) on day 1 of a 2-week cycle until disease progression, unacceptable toxicity, death, or patient/investigator decision to discontinue. Treatment-emergent adverse events (TEAEs) were evaluated, and HRQL was assessed at baseline, cycle 3, and every other cycle using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-CR29, and EuroQol 5-Dimensions 3-Levels questionnaires (NCT01571284).. Overall, 779 adult patients with mCRC, who received ≥ 1 prior oxaliplatin-based regimen and had disease progression during or following their last administration of oxaliplatin-based chemotherapy, were enrolled. At data cutoff, all patients had discontinued treatment, mainly owing to disease progression (51.7%). The most common TEAEs of any grade were diarrhea (61.6%), hypertension (48.4%), and nausea (43.3%). The most common grade 3/4 TEAEs were hypertension (24.1%), neutropenia (23.1%), and diarrhea (15.3%). Clinically meaningful changes in HRQL were reported for all measures. Most patients either had an improvement in their HRQL scores or remained stable during the treatment period based on patient-reported outcomes.. The data from this study support the tolerability of the combination of aflibercept and FOLFIRI in a setting that more closely approximates real life in patients with mCRC who failed to respond to oxaliplatin-based chemotherapy, and also suggest an improvement in HRQL.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Diarrhea; Disease Progression; Female; Fluorouracil; Follow-Up Studies; Humans; Hypertension; Leucovorin; Male; Middle Aged; Nausea; Neutropenia; Patient Reported Outcome Measures; Quality of Life; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Severity of Illness Index; Treatment Outcome; Young Adult

Chemotherapy-induced nausea and vomiting (CINV) causes significant morbidity among colorectal cancer patients, receiving fluorouracil, oxaliplatin, and leucovorin (FOLFOX) chemotherapy even with standard antiemetic prophylaxis. The purpose of this study is to determine if the addition of aprepitant to standard antiemetic therapy improves CINV in these patients.. Patients receiving FOLFOX for colorectal cancer were given antiemetic prophylaxis with aprepitant 125 mg orally on day 1 and 80 mg on days 2 and 3. Palonosetron 0.25 mg was given IV push on day 1 only. Dexamethasone 12 mg was administered orally on day 1 and 8 mg each morning on days 2 through 4. Assessments including emetic events, rescue doses, nutritional intake, and appetite were recorded in a patient diary which was returned to study personnel in the following cycle.. Of the 53 patients screened, 50 were evaluable and had a complete dataset for cycle 1. For the first cycle, 74% of patients achieved a complete response (CR), 22% achieved a major response and 4% experienced treatment failure. The percentage of patients achieving a CR remained high throughout each cycle at 83, 83, and 86% for cycles 2, 3, and 4, respectively. Appetite and nutritional status remained largely unchanged throughout treatment. Adverse events occurring in more than 10% of patients included diarrhea (13.6%), fatigue (12.6%), and neutropenia (11%).. Aprepitant added to standard antiemetic therapy appears to be an effective and safe regimen for prevention of CINV in patients receiving FOLFOX.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Colorectal Neoplasms; Dexamethasone; Female; Fluorouracil; Humans; Induction Chemotherapy; Leucovorin; Male; Middle Aged; Morpholines; Nausea; Organoplatinum Compounds; Palonosetron; Pilot Projects; Vomiting

The purpose of this phase II study was to explore the efficacy and safety of an alternating regimen consisting of folinic acid, 5-fluorouracil (5-FU) and oxaliplatin (mFOLFOX6) plus bevacizumab, and folinic acid, 5-FU and irinotecan (FOLFIRI) plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer.. Fifty-two patients with metastatic colorectal cancer received an alternating regimen consisting of four cycles of mFOLFOX6 plus bevacizumab followed by four cycles of FOLFIRI plus bevacizumab until disease progression. The primary endpoint was progression-free survival.. The median age was 60 years (range 37-75 years). Median progression-free survival was 14.2 months (95 % confidence interval [CI] 10.6-16.3) and median overall survival was 28.4 months (95 % CI 22.6-39.1). The overall response rate was 60.0 % (95 % CI 45.2-73.6). Regarding toxicity, the commonest grade 3-4 hematological adverse events were neutropenia (34.6 %) and leukopenia (7.7 %), and the commonest grade 3-4 non-hematological adverse events were anorexia (13.5 %), fatigue (9.6 %), nausea (9.6 %), and vomiting (9.6 %). Bevacizumab-related grade 3-4 adverse events included hypertension (1.9 %) and thrombosis (1.9 %).. An alternating regimen consisting of mFOLFOX6 plus bevacizumab and FOLFIRI plus bevacizumab is an effective and well-tolerated first-line chemotherapy combination for patients with metastatic colorectal cancer.

Topics: Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Disease-Free Survival; Fatigue; Female; Fluorouracil; Humans; Hypertension; Leucovorin; Leukopenia; Male; Middle Aged; Nausea; Neutropenia; Organoplatinum Compounds; Survival Rate; Thrombosis; Vomiting

In mouse models of pancreatic cancer, IPI-926, an oral Hedgehog inhibitor, increases chemotherapy delivery by depleting tumor-associated stroma. This multicenter phase Ib study evaluated IPI-926 in combination with FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, oxaliplatin) in patients with advanced pancreatic cancer.. Patients were treated with once-daily IPI-926 plus FOLFIRINOX. A 3 + 3 dose escalation design was used, with cohort expansion at the maximum tolerated dose. A subset of patients underwent perfusion computed tomography to assess changes in tumor perfusion.. The maximum tolerated dose was identified 1 dose level below standard FOLFIRINOX. Common treatment-related adverse events included liver function test abnormalities, neuropathy, nausea/vomiting, and diarrhea. Objective response rate was high (67%), and patients receiving IPI-926 maintenance showed further declines in CA19-9 levels even after FOLFIRINOX discontinuation. Treatment did not result in consistent increases in tumor perfusion. The study closed early when a separate phase II trial of IPI-926 plus gemcitabine indicated detrimental effects of this combination.. This is the first study to demonstrate the feasibility of using FOLFIRINOX as the chemotherapeutic backbone in a clinical trial design. Although robust antitumor activity and acceptable safety were observed with the addition of IPI-926 to this regimen, future development of Hedgehog inhibitors in pancreatic cancer seems unlikely.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; CA-19-9 Antigen; Camptothecin; Diarrhea; Dose-Response Relationship, Drug; Feasibility Studies; Female; Fluorouracil; Hedgehog Proteins; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Nausea; Nervous System Diseases; Organoplatinum Compounds; Oxaliplatin; Pancreatic Neoplasms; Signal Transduction; Treatment Outcome; Veratrum Alkaloids; Vomiting

The granisetron transdermal system (GTS) showed non-inferior efficacy to oral granisetron to control chemotherapy-induced nausea and vomiting (CINV) during multiday chemotherapy. We compared the efficacy and safety of GTS with that of intravenous and oral granisetron in Korean patients receiving moderately emetogenic chemotherapy (MEC).. A total of 276 patients were randomized into GTS (n = 139, one patch on days 1-4) or control group (n = 137, intravenous on day 1 and oral on days 2-4). The primary endpoint was the percentage of patients achieving complete response (CR) from chemotherapy initiation until 24 h after the final administration.. Out of 234 patients (112 in GTS and 122 in control group) included in the per protocol analysis, 97.9 % had gastrointestinal cancer and 76.9 % received 3-day chemotherapy. The GTS showed non-inferior efficacy achieving CR in 75.0 % of the patients; 74.6 % of the patients in the control group achieved CR (95 % confidence interval -10.73 to 11.55 %). The CR rate did not change after subgroup analyses by sex, age, and chemotherapy naivety and analysis per day and overall days of treatment. The GTS group showed sustained CR from day 1 to day 4. Patients' satisfaction, assessed using Functional Living Index-Emesis (FLI-E), showed no difference. Both treatments were well tolerated and safe.. The GTS showed non-inferior efficacy to intravenous and oral granisetron. The safety, tolerability, and FLI-E scores of the GTS were comparable to those of control group. The GTS offers a convenient alternative option for relieving CINV in patients receiving MEC.

Topics: Administration, Cutaneous; Adult; Aged; Antiemetics; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Female; Fluorouracil; Granisetron; Humans; Leucovorin; Male; Middle Aged; Nausea; Neoplasms; Organoplatinum Compounds; Prospective Studies; Remission Induction; Republic of Korea; Safety; Vomiting

The oral neurokinin-1 antagonist aprepitant is recommended in several guidelines for preventing chemotherapy-induced nausea & vomiting (CINV) due to highly emetogenic cancer chemotherapy. Little is known about the feasibility and safety of aprepitant in patients treated with oxaliplatin.. In this multicentre, open label, randomised, phase 3 trial, we recruited patients with colorectal cancer who underwent an oxaliplatin-based chemotherapy. Patients were centrally randomised in a 1:1 ratio to the control group (5-HT3-receptor antagonist+dexamethasone) or aprepitant group (5-HT3-receptor antagonist+dexamethasone+aprepitant or fosaprepitant) in the first course. All patients were treated with aprepitant/fosaprepitant therapy in the second course. The primary end-point was the proportion of patients with no emesis.. A total of 413 patients entered this clinical trial from 25 centres in Japan. Significantly more patients in the aprepitant group achieved no vomiting overall and delayed phase than those in the control group (95.7% versus 83.6%, and 95.7% versus 84.7%, respectively). The aprepitant group also had statistically significantly higher percentages of no significant nausea, complete response and complete protection than the control group overall. In the control group, the percentages of no vomiting were higher in the second cycle than in the first cycle. The incidence of vomiting occurred day 7 or later was significantly higher in the control group compared with the aprepitant group. Other adverse events were not significant between the groups.. The aprepitant therapy was more effective than the control therapy for prevention of CINV in colorectal cancer patients receiving an oxaliplatin-based regimen.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Drug Therapy, Combination; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Morpholines; Nausea; Organoplatinum Compounds; Oxaliplatin; Oxaloacetates; Vomiting

The oral PI3K inhibitor BKM120 has been reported as safe and well tolerated in early phase clinical trials of advanced cancer patients. We performed a phase I trial of BKM120 plus mFOLFOX6 (5-FU/LV + oxaliplatin), a common chemotherapeutic backbone in GI malignancies, to establish the maximum tolerated dose (MTD) and characterize the safety and tolerability of the combination.. Patients with advanced solid tumors received oral BKM120 daily combined with standard doses of mFOLFOX6 every 2 weeks of a 28 day cycle. The study utilized a standard 3 + 3 dose escalation schema.. A total of 17 patients received treatment with BKM120, 13 of which were evaluate for dose limited toxicity (DLT). The most common tumor types were colorectal cancer, cholangiocarcinoma, pancreatic cancer and hepatocellular carcinoma. DLT included grade 3 hyperglycemia, grade 3 AST/ALT elevation, grade 4 neutropenia and grade 4 thrombocytopenia. A total of 76 % of patients experienced treatment related grade 3/4 adverse events (AEs), the most common of which were neutropenia, fatigue, leukopenia, hyperglycemia and thrombocytopenia. One patient demonstrated an unconfirmed partial response and three patients had stable disease.. The MTD of BKM120 in combination with standard doses of mFOLFOX6 was 40 mg daily, which is well below the 100 mg daily dose proven effective and tolerable both as a single agent and in combination with other chemotherapeutics. In addition, the regimen of BKM120 with mFOLFOX6 in patients with refractory solid tumors resulted in increased toxicity than would be expected from either the PI3K inhibitor or the chemotherapy backbone alone.

Topics: Administration, Oral; Adult; Aged; Aminopyridines; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Organoplatinum Compounds; Phosphoinositide-3 Kinase Inhibitors

Previous reports of the influence of UGT1A1 gene polymorphisms on the pharmacokinetics of irinotecan metabolism have not assessed Asian patients treated with FOLFIRI plus bevacizumab for advanced and recurrent colorectal cancer. Twenty-one Japanese colorectal cancer patients received intravenous FOLFIRI (bolus irinotecan, folinic acid, and fluorouracil followed by 46-hour fluorouracil infusion) followed by bevacizumab (5 mg/kg) in Cycle 1. In Cycle 2, patients received bevacizumab followed by FOLFIRI. The regimen was in 2-week cycles. The area under-the-curves ratio (AUC0-last) (Cycle 2/Cycle 1) was determined from plasma concentrations of irinotecan and metabolites (SN-38, SN-38G). Safety, efficacy, and drug-drug interactions were analyzed. Median observation period was 7.8 months; median number of cycles 15. Drug-drug interactions were evaluated in eight patients without irinotecan dose reduction. Mean AUC0-last ratios (with/without bevacizumab) of irinotecan, SN-38, and SN-38G were 0.959, 0.927, and 0.931 respectively. Response rate was 65%; median progression-free survival 16.4 months. Response occurred in four patients with, and nine without, UGT1A1 polymorphism. No significant differences occurred between efficacy, safety, or polymorphism status. This cohort showed no differences in safety or efficacy compared to previous reports. Bevacizumab did not affect the pharmacokinetics of irinotecan and its metabolites, irrespective of UGT1A1 polymorphism status.

Topics: Adult; Aged; Anorexia; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Asian People; Bevacizumab; Camptothecin; Colorectal Neoplasms; Diarrhea; Drug Interactions; Female; Fluorouracil; Glucuronosyltransferase; Humans; Leucovorin; Male; Middle Aged; Nausea; Neutropenia; Treatment Outcome

Adverse events associated with 5-fluorouracil (5FU) based adjuvant therapy in colorectal cancer (CRC) patients may predict survival. We studied whether haematological (leucopenia, neutropenia, thrombocytopenia) or non-haematological (mucositis, diarrhoea, nausea/vomiting, hand-foot syndrome or other toxicity) adverse events were associated with disease-free survival (DFS) or overall survival (OS) in a large patient material treated with 5-fluorouracil based adjuvant chemotherapy.. Data from two prospective randomised adjuvant trials were combined to achieve a dataset of 1033 radically operated stage II and III CRC patients treated with either monthly 5FU and leucovorin (LV) as bolus injections (Mayo or modified Mayo) or bi-monthly with bolus and continuous infusion (LV5FU2 or simplified LV5FU2). Toxicities were recorded at each treatment cycle according to NCI-C CTC (the Common Toxicity Criteria of the National Cancer Institute of Canada). The worst toxicity grade was taken into account. The median follow-up time of patients was 6.05 years.. 47% of patients developed neutropenia, 54% nausea/vomiting and 43% mucositis. Any grade neutropenia was associated with improved DFS (hazard ratio (HR) 0.81), any grade nausea/vomiting with improved DFS (HR 0.79) and OS (HR 0.62) and mucositis with improved DFS (HR 0.74) and OS (HR 0.72). Patients experiencing no predefined toxicity had the worst outcome.. Specific adverse events related to adjuvant fluorouracil chemotherapy are associated with improved DFS and OS in early stage CRC patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colorectal Neoplasms; Diarrhea; Disease-Free Survival; Female; Fluorouracil; Hand-Foot Syndrome; Hematologic Diseases; Humans; Leucovorin; Male; Middle Aged; Mucositis; Nausea; Prospective Studies; Treatment Outcome; Vomiting

Previous studies have suggested the potential importance of three DPYD variants (DPYD*2A, D949V, and I560S) with increased 5-FU toxicity. Their individual associations, however, in 5-FU-based combination therapies, remain controversial and require further systematic study in a large patient population receiving comparable treatment regimens with uniform clinical data.. We genotyped 2886 stage III colon cancer patients treated adjuvantly in a randomized phase III trial with FOLFOX or FOLFIRI, alone or combined with cetuximab, and tested the individual associations between functionally deleterious DPYD variants and toxicity. Logistic regressions were used to assess univariate and multivariable associations. All statistical tests were two-sided.. In 2594 patients with complete adverse event (AE) data, the incidence of grade 3 or greater 5FU-AEs in DPYD*2A, I560S, and D949V carriers were 22/25 (88.0%), 2/4 (50.0%), and 22/27 (81.5%), respectively. Statistically significant associations were identified between grade 3 or greater 5FU-AEs and both DPYD*2A (odds ratio [OR] = 15.21, 95% confidence interval [CI] = 4.54 to 50.96, P < .001) and D949V (OR = 9.10, 95% CI = 3.43 to 24.10, P < .001) variants. Statistical significance remained after adjusting for multiple variables. The DPYD*2A variant statistically significantly associated with the specific AEs nausea/vomiting (P = .007) and neutropenia (P < .001), whereas D949V statistically significantly associated with dehydration (P = .02), diarrhea (P = .003), leukopenia (P = .002), neutropenia (P < .001), and thrombocytopenia (P < .001). Although two patients with I560S had grade≥3 5FU-AEs; a statistically significant association could not be demonstrated because of its low frequency (P = .48).. In the largest study to date, statistically significant associations were found between DPYD variants (DPYD*2A and D949V) and increased incidence of grade 3 or greater 5FU-AEs in patients treated with adjuvant 5-FU-based combination chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Aspartic Acid; Camptothecin; Chemotherapy, Adjuvant; Colonic Neoplasms; Diarrhea; Dihydrouracil Dehydrogenase (NADP); Drug-Related Side Effects and Adverse Reactions; Female; Fluorouracil; Genetic Predisposition to Disease; Humans; Leucovorin; Logistic Models; Male; Middle Aged; Nausea; Neoplasm Staging; Neutropenia; Organoplatinum Compounds; Polymorphism, Single Nucleotide; Prospective Studies; Severity of Illness Index; Thrombocytopenia; Valine; Vomiting

This study aimed to compare the efficacy and toxicity of weekly paclitaxel plus S-1 with weekly paclitaxel plus 5-fluorouracil in treating advanced gastric cancer as first line regimen. The primary end-point was disease control rate (DCR).. Patients with advanced or recurrent gastric cancer were randomly assigned to an experimental arm or a control arm. The experimental arm's dosage schedule was paclitaxel 60 mg/m2 (intravenous infusion) on days 1, 8 and 15 and S-1 80-120 mg/d (oral administration) on days 1-14. Control arm patients were given the same paclitaxel, combined with 5-fluorouracil 500 mg/m2 (continuous intravenous infusion) on days 1-5; and leucovorin 20 mg/m2 (intravenous infusion) on days 1-5. All schedules were repeated every 28 d.. A total of 240 patients were enrolled and equally randomised into two arms. The overall response rate and DCR of the experimental arm was non-inferior to that of the control arm both in the per-protocol set and the full analysis set. The secondary end-point median progression-free survival (PFS) of the experimental and control arms was 153 and 129 d, with the hazard ratio of 0.641 (95% CI: 0.473-0.868, P = 0.004). The hazard ratio of the time to treatment failure of the two arms was 1.449 (95% CI: 0.705-2.980, P = 0.229). The six-month PFS rates of both arms were similar (31.3% versus 31.8%, P = 0.94). Cox regression analysis indicated that only treatment regimen and age were independent predictive factors for PFS. The most common adverse events were haematological and gastrointestinal. The rates of grade 3-4 adverse events were not significantly different between the two study arms and were mostly lower than 5%.. Weekly paclitaxel combined with S-1 is an active and well-tolerated regimen, supporting the view that S-1 can be an alternative for infusional 5-fluorouracil for advanced gastric cancer.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Leucovorin; Leukopenia; Male; Middle Aged; Multivariate Analysis; Nausea; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Treatment Outcome; Young Adult

Topics: Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Benztropine; Camptothecin; Dexamethasone; Drug Combinations; Female; Fluorouracil; Haloperidol; Humans; Leucovorin; Male; Metoclopramide; Morpholines; Nausea; Organoplatinum Compounds; Pancreatic Neoplasms; Vomiting

This phase II study examined the efficacy and safety of alternating regimens of mFOLFOX6 and FOLFIRI as a first-line treatment for unresectable or metastatic colorectal cancer.. Forty-eight patients were enrolled in this study. Patients received an alternating regimen of 4 cycles of mFOLFOX6 followed by 4 cycles of FOLFIRI.. The characteristics of the study population were as follows: males/females 34/12, median age 66 years (range 43-75) and Eastern Cooperative Oncology Group performance status 0/1/2 in 37/9/0 patients. The overall response rate was 58.7% [95% confidence interval (CI) 43.9-73.5]. The median progression-free survival was 10.3 months (95% CI 7.5-11.9), and the median overall survival was 28.4 months (95% CI 22.5-35.7). Among the 47 patients evaluated for toxicity, the most common grade 3-4 adverse events were leukopenia (26%), neutropenia (55%), anemia (4%), neurotoxicity (0%), diarrhea (2%), febrile neutropenia (4%), nausea (4%), vomiting (2%), and hypersensitivity (0%).. The results of this phase II study indicate that this alternating schedule is effective and well tolerated as a first-line treatment for unresectable or metastatic colorectal cancer. The low rate of grade 3 neurotoxicity is also promising.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil; Humans; In Vitro Techniques; Leucovorin; Middle Aged; Nausea; Neutropenia; Organoplatinum Compounds; Treatment Outcome; Vomiting

The aim of this study was to assess the use of 5-fluorouracil (5-FU), leucovorin and oxaliplatin (FOLFOX) regimens in clinical practice according to their efficacy and toxicity.. Patients who received oxaliplatin-containing regimens after curative resection for colorectal carcinoma from 10 different oncology centers between May 2004 and December 2009 were included in the study. All patients were treated with FOLFOX regimens. Patients with rectal carcinoma were also treated with chemoradiotherapy with 5-FU after 2 cycles of a FOLFOX regimen.. The median age of the patients was 56 years (range 17-78). Of the total 667 patients, 326 were given FOLFOX-4, 232 were given modified FOLFOX-4 and 109 were given FOLFOX-6. The distribution according to disease stage was 33 patients with stage IIIA colorectal cancer, 382 patients with stage IIIB and 252 patients with stage IIIC. The most common adverse events were neutropenia (54%), nausea (36.9%), neuropathy (38.2%) and anemia (33.1%) for all grades. The median follow-up time was 23 months (range 1-79). Three-year disease-free survival and overall survival were 65 and 85.7%, respectively.. The different oxaliplatin-containing 5-FU-based adjuvant chemotherapy regimens in patients with stage III colorectal cancer seemed to be at least equal in terms of efficacy regardless of the method of 5-FU administration or oxaliplatin dose.

Topics: Adolescent; Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Colorectal Neoplasms; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Nausea; Neutropenia; Organoplatinum Compounds; Retrospective Studies; Treatment Outcome; Young Adult

Indisetron is a serotonin (5-hydroxytryptamine type 3) receptor antagonist that also antagonizes 5-hydroxytryptamine type 4 receptors. We designed a pilot study in order to explore the optimal dosing period for indisetron during modified FOLFOX6 (mFOLFOX6).. Forty-two chemotherapy-naive patients with advanced colorectal cancer scheduled to receive mFOLFOX6 were randomly assigned to either a 1- or 3-day indisetron regimen arm. The primary endpoint was complete protection from vomiting.. Proportions of patients with complete protection from vomiting were 85.7% [95% confidence interval (CI) 63.7-97.0] with the 3-day regimen and 81.0% (95% CI 58.1-94.6) with the 1-day regimen. Proportions of patients with complete protection from nausea were 47.6% in each arm (95% CI 25.7-70.2). No rescue therapy rates were 66.7% (95% CI 43.0-85.4) versus 57.1% (95% CI 34.0-78.2). No severe adverse events were observed in either arm.. Both 1- and 3-day indisetron regimens were feasible for preventing nausea and vomiting induced by mFOLFOX6.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Colorectal Neoplasms; Drug Administration Schedule; Feasibility Studies; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Nausea; Organoplatinum Compounds; Pilot Projects; Pyrazoles; Serotonin 5-HT3 Receptor Antagonists; Serotonin 5-HT4 Receptor Antagonists; Treatment Outcome; Vomiting

To evaluate the efficacy and safety of FOLFIRI regimen in patients with advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin.. The FOLFIRI regimen consisted of intravenous infusion of irinotecan 180 mg/m(2) on day 1 plus leucovorin (LV) 400 mg/m(2) on day 1 plus 5-fluorouracil (5-FU) 400 mg/m(2) bolus on day 1 plus 46-hour intravenous infusion of 5-FU 2,400 mg/m(2), every 2 weeks as one cycle. The main selection criterion for this study was the advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin.. Of the 57 evaluable patients for efficacy, 4 (7.5%) had a partial response, 36 (67.9%) had stable disease, and 13 (24.5%) had progressive disease. Median progression-free survival was 4.8 months (95% CI 3.9-5.7 months), and median overall survival was 7.8 months (95% CI 13.1-16.5 months). Safety analysis was based on the data of 57 evaluable patients. The most frequently observed grade 3 or 4 toxicities were neutropenia 16 (27.8%), nausea/vomiting 7 (12.3%), and diarrhea 1 (1.8%).. FOLFIRI regimen is effective and well tolerated in patients with advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin in Chinese population.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; China; Colorectal Neoplasms; Diarrhea; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Nausea; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Pyrimidines; Survival; Vomiting; Young Adult

Phase II studies have shown that the combination of capecitabine and irinotecan (the XELIRI regimen) is active in metastatic colorectal cancer (MCRC). There are, however, no data about the use of the XELIRI regimen in the neoadjuvant treatment.. Patients with unresectable liver-only metastases of MCRC with < or = 75 years of age were randomised to either the XELIRI (irinotecan 250 mg/m(2) given on day one and capecitabine 1000 mg/m(2) twice daily from day 2-15, every 21 days) or the FOLFIRI arm (irinotecan 180 mg/m(2), 5-FU 400 mg/m(2), LV 200 mg/m(2), 5-FU 2400 mg/m(2) (46-h infusion)--all given on day one, every 14 days). Primary end points were objective response rate (ORR) and rate of radical (R0) surgical resection. Secondary end points were progression-free survival (PFS), overall survival (OS) and safety.. Altogether 87 patients were enrolled (41 pts in the XELIRI and 46 pts in the FOLFIRI arm). The median age was 63 years (63 years in the XELIRI and 62 years in the FOLFIRI arm) (p = 0.33). ORR was 49% in the XELIRI and 48% in the FOLFIRI arm (p = 0.76). The rate of radical R0 resection was 24% in both arms of patients. At the end of treatment, 37% of patients in the XELIRI and 26% of patients in the FOLFIRI arm were without evidence of the disease (CR+R0 resection) (p = 0.56). There were no statistical differences in grade 3 or 4 adverse events between both arms: diarrhoea 7% vs. 6%, neutropenia 5% vs. 13%, ischemic stroke 0 vs. 2%, acute coronary syndrome 2% vs. 4%, respectively. At the median follow up of 17 (range 1-39) months, the median PFS was 10.3 months in the XELIRI and 9.3 months in the FOLFIRI arm (p = 0.78), the median OS was 30.7 months in the XELIRI arm and 16.6 months in the FOLFIRI arm (p = 0.16).. The XELIRI regimen showed similar ORR as the FOLFIRI regimen in the neoadjuvant treatment of patients with MCRC. In addition, the XELIRI regimen showed similar PFS and OS with acceptable toxicity compared to the FOLFIRI regimen.. Current Controlled Trials ISRCTN19912492.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Diarrhea; Fatigue; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Male; Middle Aged; Nausea; Neoadjuvant Therapy; Neutropenia; Prospective Studies; Survival Analysis; Treatment Outcome

To evaluate the efficacy and safety of the combination of oxaliplatin and ELF (VP16/CF/5-Fu) regimen in the treatment of patients with advanced gastric cancer.. Oxaliplatin was given at a dose of 100 mg/m(2) i.v. 2 hours D1, calcium folinate (CF) 200 mg/m(2) i.v. 1/2 hour D1 approximately D3, 5-fluorouracil (5-Fu) 500 mg/m(2) i.v. 2 hours D1 approximately D3 and etoposide 100 mg/m(2) i.v. 3 hours D1 approximately D3. Cycles were repeated every 21 days. Efficacy and safety were evaluated every 2 cycles.. Sixty-nine patients were enrolled into the study. All cases were pathologically confirmed as gastric cancer (adenocarcinoma in 57 cases and signet ring cell carcinoma in 12 cases). 42 patients had newly diagnosed disease, and 27 patients had received previous chemotherapy. 62 patients were analyzed for response (7 complete responses and 25 partial responses) with total response rate 51.61%. The median time to progression was 5.7 months and the median overall survival was 9.2 months. The most common hematologic toxicities were anemia (29.0%), leucopenia (51.2%) and thrombocytopenia (21.2%). No grade 4 and grade 5 hematologic toxicities were observed. The most common non-hematologic toxicities were nausea (46.5%), vomiting (41.1%), peripheral sensory neuropathy (47.1%), and grade 2 alopecia (27.3%).. This oxaliplatin combined with ELF regimen shows good efficacy and acceptable safety in advanced gastric cancer patients. It is worthy to be proved as a suitable alternative regimen in this indication.

Topics: Adenocarcinoma; Adult; Aged; Anemia; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Levoleucovorin; Male; Middle Aged; Nausea; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Remission Induction; Stomach Neoplasms; Survival Rate; Thrombocytopenia; Vomiting

Irinotecan (CPT-11), oxaliplatin, 5-fluorouracil (5-FU) and capecitabine are main active agents for advanced colorectal cancer. FORFIRI regimen is recommended for the patients who were treated with oxaliplatin plus 5-FU or capecitabine previously. This study was to investigate the efficacy and safety of FORFIRI regimen in treating advanced colorectal cancer failing to prior oxaliplatin-based chemotherapy, and analyze the impacts of clinical factors on the responses.. A total of 90 patients with advanced colorectal adenocarcinoma, who had received prior adjuvant FOLFOX6 regimen and progressed within 12 months after the completion of therapy or had no response to prior FOLFOX6/CapeOX regimen as first-line therapy, were treated with FORFIRI regimen. The efficacy and adverse events were observed.. Of the 81 evaluable patients, two achieved complete remission, 20 achieved partial remission and 34 had stable disease. The overall response rate was 27.2% and disease control rate was 69.1%. The median time to progression was 6.8 months (95% CI, 4.9-8.8 months) and median overall survival time was 18.8 months (95% CI, 17.5-20.2 months). The main adverse events time were nausea, vomiting, neutropenia, alopecia, fatigue, impaired liver function, oral mucositis and diarrhea. Grade III adverse events included alopecia in 15 patients (16.7%), vomiting in 10 patients (11.1%), nausea in eight patients (8.9%), neutropenia in five patients (5.6%), impaired liver function in two patients (2.2%) and oral mucositis in two patients (2.2%).. FOLFIRI regimen is effective and well-tolerated as salvage therapy for advanced colorectal cancer failing to prior FOLFOX6/CapeOX regimen, and thus can be used widely.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Disease Progression; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Nausea; Neoplasm Staging; Neutropenia; Rectal Neoplasms; Remission Induction; Salvage Therapy; Survival Rate; Vomiting; Young Adult

This phase II study was designed to assess the safety and efficacy of a modified FOLFIRI regimen (irinotecan with bi-weekly, low dose leucovorin (ldLV) and bolus and continuous infusion with 5-fluorouracil (5-FU)) as a salvage therapy for patients with advanced or metastatic gastric cancer.. Patients were treated with irinotecan 150 mg/m(2) on day 1 and received ldLV 20 mg/m(2) followed by 5-FU 400 mg/m(2) (bolus) and 5-FU 600 mg/m(2) (22 h continuous infusion) on days 1 and 2 every 14 days.. A total of 36 patients were assigned to treatment. The median patient age was 55 years (range 31-70), and 55.6% (20/36) of the patients had performance status (ECOG) of 0 or 1. The median follow-up duration was 15.5 (range 2.6-36.4) months. Of the 30 patients evaluated for their tumor response, three achieved a partial response, with an overall response rate of 10.0% (95% CI 0.0-21.0%). Eleven patients (36.7%) showed stable disease. The median time to progression was 3.3 (95% CI 2.0-4.6) months, and the median overall survival time was 10.9 (95% CI 6.1-15.7) months. The median number of cycles of modified FOLFIRI treatment was 3 (range 1-9 cycles). Grade III or IV neutropenia was observed in 23 cycles (17.6%), and febrile neutropenia occurred in three cycles (2.3%). Grade III nausea/vomiting was found in one patient (2.8%). There was one episode of UGI bleeding, but there were no treatment-related deaths.. The modified FOLFIRI regimen described here appears a safe and feasible salvage therapy in advanced gastric cancer patients.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Female; Fluorouracil; Follow-Up Studies; Hematologic Diseases; Humans; Leucovorin; Male; Middle Aged; Nausea; Salvage Therapy; Stomach Neoplasms; Stomatitis; Survival Rate; Treatment Outcome

Clinical studies regarding chemotherapy for gastric cancer patients with malignant ascites have been classically rather limited in scope, largely because peritoneal seeding produces no measurable lesions, and patients generally exhibited poor performance status. Herein, we have evaluated the efficacy and toxicity of a fortnightly modified FOLFOX-4 (m-FOLFOX) regimen.. Gastric cancer patients with cytologically confirmed malignant ascites were treated with cycles of oxaliplatin at 85 mg/m(2) plus leucovorin 20 mg/m(2) on the first day of treatment, followed by 5-fluorouracil (5-FU) via a 400 mg/m(2) bolus and a 22 h continuous infusion of 600 mg/m(2) 5-FU on Days 1-2 at 2-week intervals.. Forty-eight patients participated in this study. Twenty-two patients (45.8%) were treated with m-FOLFOX-4 as a first line palliative treatment. Twenty-one patients (43.8%) were adjudged to have an Eastern Cooperative Oncology Group (ECOG) performance status of 2. Thirty-six patients were assessable and exhibited measurable lesions. Twelve (33.3%) patients evidenced partial responses. Decreases or disappearances of ascites levels were observed in 17 (35.4%) patients. The median time to progression and overall survival time were 3.5 (95% CI: 2.9-4.1) months and 8.4 (95% CI: 4.9-11.9) months, respectively. Major hematologic toxicities included Grades 1-2 anemia (53.9%), neutropenia (41.6%) and, Grades 3-4 neutropenia (15.8%). The most frequently detected non-hematological toxicities were Grades 2 and 3 nausea/vomiting (17%). We noted no deaths related to treatment.. The m-FOLFOX-4 regimen utilized herein was determined to be both safe and feasible even for gastric cancer patients with malignant ascites in poor performance status.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Ascites; Carcinoma; Disease-Free Survival; Drug Administration Schedule; Feasibility Studies; Female; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Nausea; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Palliative Care; Stomach Neoplasms; Survival Analysis; Treatment Outcome; Vomiting

Several clinical trials have demonstrated that oxaliplatin is a useful agent in combination with 5-fluorouracil (5-FU) and folinic acid (FA) for the treatment of patients with colorectal carcinoma. The aims of this pilot study were to evaluate non-hematological toxicity and patient characteristics in gastrointestinal cancer patients treated with chronomodulated chemotherapy consisting of oxaliplatin, 5-FU and sodium folinate.. Patients with metastatic gastrointestinal cancer received a chronomodulated regimen with oxaliplatin (25 mg/m2), 5-FU (750 mg/m2) and sodium folinate (150 mg/m2). Non-hematological toxicities were evaluated and analyzed in relation to patient characteristics, i.e. age, sex, body weight, body mass index (BMI), body surface area and smoking status. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria.. The severity of non-hematological toxicity was generally moderate. Grade 4 toxicity was only found in 2 patients with diarrhea (12.5%). The most frequent common adverse events were nausea, Grades 1 - 2 in 13 patients (81.3%), followed by motor neuropathy, Grades 1 - 3 in 11 patients (68.9%). The analyses showed that patient characteristics such as BMI and smoking status were associated with mucositis/stomatitis, vomiting or mood alteration. Furthermore, there was a relationship between smoking status and the overall non-hematological toxicity. Smokers had significantly higher overall toxicity than non-smokers and body mass index correlated significant with overall toxicity.. The results of this pilot investigation suggest that a chronomodulated regimen with oxaliplatin, 5-FU and sodium folinate has a manageable non-hematological toxicity profile and that toxicity of the chronomodulated schedule studied depends on the patient characteristics. In further investigations, risk factors determining chemotherapeutic toxicity should be considered. Because of the small number of patients in this pilot investigation, the findings need to be confirmed in a larger clinical study.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Body Mass Index; Chronotherapy; Diarrhea; Female; Fluorouracil; Gastrointestinal Neoplasms; Humans; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Male; Middle Aged; Motor Neurons; Mucositis; Nausea; Organoplatinum Compounds; Oxaliplatin; Patient Selection; Pilot Projects; Risk Factors; Severity of Illness Index; Stomatitis; Vomiting

Infusional fluorouracil (5-FU) and leucovorin (LV) with oxaliplatin is one of the current standard regimens for the treatment of patients with metastatic colorectal cancer. Weekly bolus 5-FU with high-dose LV (Roswell Park Memorial Institute Regimen: RPMI) is the most commonly used regimen in Japan. The objectives of this study were to determine the recommended dose (RD) of RPMI combined with oxaliplatin and to evaluate the toxicity and efficacy at the RD.. The subjects were 18 patients with metastatic colorectal cancer. Oxaliplatin (85 mg/m2) was given intravenously over 2 h on days 1 and 15 with l-LV (250 mg/m2) given intravenously over 2 h and 5-FU as an intravenous bolus on days 1, 8, and 15. This treatment was repeated every 4 weeks. The dose of 5-FU was escalated from 400 mg/m2 (level 1) to 500 mg/m2 (level 2).. A total of 14 patients received level 1, and 4 received level 2. Three of the patients had dose-limiting toxicity (DLT) in cycle 1 of level 2 (grade 3 thrombocytopenia, grade 4 neutropenia and grade 2 neutropenia in one patient each), requiring that treatment was delayed for longer than 7 days. None of the 14 patients given level 1 had DLT or grade 3 or 4 gastrointestinal toxicity. Sensory neuropathy occurred in all patients. Objective response rates were 61% in the 18 patients studied and 64% at level 1. The median time to progression was 171 days, and the median overall survival time was 603 days in the 18 patients studied.. Oxaliplatin (85 mg/m2) with weekly bolus 5-FU (400 mg/m2) and high-dose l-LV (250 mg/m2) is recommended for further phase III studies in patients with metastatic colorectal cancer.

Topics: Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Nausea; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Peripheral Nervous System Diseases; Rectal Neoplasms; Remission Induction; Survival Rate

Combination chemotherapy with 5-fluorouracil (5-FU) and cisplatin is regarded as the standard regimen for advanced esophageal carcinoma. This study was to evaluate the efficacy and safety of DLF, CLF and DFM regimens, based on platinum compound plus 5-fluorouracil in the treatment of advanced esophageal carcinoma, and to further explore prognostic factors of advanced esophageal carcinoma.. From October 1999 to December 2004, 98 patients with advanced esophageal carcinoma were enrolled in the study. They were non-randomly assigned to receive a 2-hour infusion of folinic acid 200 mg/m(2), followed by a 5-FU bolus 400 mg/m(2) and 48-hour infusion of 5-FU 3,000 mg/m(2) every 3 weeks, combined with cisplatin 80 mg/m(2) (DLF, n=48) or with carboplatin AUC=5 on day 1 (CLF, n=32), or with cisplatin 80 mg/m(2), 5-fluorouracil bolus 400 mg/m(2) on day 1-5 plus pingyangmycin 5 mg/m(2) on day 1, 3, 5 (DFM, n=18). Survival analysis and prognostic factors were evaluated by Kaplan-Meier method and Cox regression analysis.. All 98 patients were assessable for response and toxicity. There were 13 complete response, 36 partial response, 45 no changes and 4 progressive disease with a total response rate of 46.86%. The response rates of DLF, CLF and DFM regimens were 60.42%,46.86% and 27.78%, respectively (DLF vs DFM, P=0.027). The major side effects were nausea-vomiting, alopecia, bone marrow suppression and mucositis, and the others were uncommon. All side effects were tolerable and mild except for nausea-vomiting. Nausea-vomiting was mildest in CLF among the three regimens. After a median follow-up of 9 months, the overall median survival was 9 months (95% CI, 6.67 to 11.33 months), the median survival of the patients treated with DLF, CLF or DFM regimen was 10, 9 and 7 months, respectively (P=0.7402). Better prognosis was correlated with good conditions of patients before chemotherapy (KPS> or =80, P=0.000) and metastasis to lymph node, parenchyma or bone in stead of visceral organs (P=0.026). There was no correlation between the prognosis and age, sex, types of pathology and the regimen of therapy.. The DLF regimen is tolerable and more effective, thus could be recommended as a front-line standard treatment for advanced esophageal carcinoma. The CLF regimen is more suitable for feeble and older patients since it has the mildest side effects. The prognostic factors of advanced esophageal carcinoma include conditions before chemotherapy and the location of metastasis.

Topics: Adenocarcinoma; Adult; Aged; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carboplatin; Carcinoma, Squamous Cell; Cisplatin; Esophageal Neoplasms; Female; Fluorouracil; Follow-Up Studies; Humans; Infusions, Intravenous; Leucovorin; Leukopenia; Lymphatic Metastasis; Male; Middle Aged; Nausea; Neoplasm Staging; Proportional Hazards Models; Remission Induction; Survival Rate

To evaluate the efficacy and safety of modified FOLFIRI regimen in advanced colorectal cancer (CRC) patients refractory to fluoropyrimidine and oxaliplatin.. The modified FOLFIRI regimen consisted of intravenous infusion of irinotecan 180 mg/m2 d1 + LV 200 mg/m2 dl + 5-Fu 400 mg/m2 bolus dl plus 46-hour intravenous infusion of 5-Fu 2.4 g/m2, every 2 weeks as one cycle. The main selection criterion for this study was the advanced CRC refractory to fluoropyrimidine and oxaliplatin.. Of the 80 evaluable patients for efficacy: 10 (12.5%) had a partial response, 51 (63.7%) stable disease, and 19 (23.8%) progressive disease. The median time to progression was 96 days. Safety analysis was based on the data of 83 evaluable patients. The most frequently observed grade 3 or 4 toxicities were neutropenia (24.1%), nausea/vomiting (8.4%), and diarrhea (2.4%).. Modified FOLFIRI regimen is effective and well tolerated in patients with advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Diarrhea; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Nausea; Neoplasm Staging; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Prospective Studies; Pyrimidines; Rectal Neoplasms; Remission Induction; Treatment Failure

A clinical study has been conducted since August 2001 to investigate whether chemotherapy with CPT-11/l-LV/ 5-FU/UFT could be an effective regimen for advanced or recurrent colorectal cancer. The chemotherapy consisted of CPT-11 30 mg/m2 iv, as a 120-minute infusion, followed by l-LV 30 mg/m2, as a 60-minute infusion, followed by 5-FU 300 mg/m2, as a 120-minute infusion. This treatment was administered weekly for 6 weeks followed by a 2-week rest period and repeated every 8 weeks. UFT (250 mg/m2/day) was orally administered daily. All patients were evaluable for efficacy, 2 CR, 5 PR, 3 SD and 7 PD. The overall response rate was 41.1% with a median time to progression of 7.1 months and a median survival time of 12.0 months. No grade 3/4 toxicities were observed. The present study suggests that combination chemotherapy with CPT-11, l-LV, 5-FU, and UFT is well tolerated and might be a promising regimen for advanced or recurrent colorectal cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Male; Middle Aged; Nausea; Rectal Neoplasms; Survival Rate; Tegafur; Uracil; Vomiting, Anticipatory

To assess the feasibility and activity of a combination schedule with irinotecan (CPT-11), oxaliplatin (L-OHP), brief infusional fluorouracil (5-FU) and folinic acid (FA) as first-line treatment in metastatic colorectal cancer (MCC) patients.. Fifty consecutive patients were treated with CPT-11 125 mg/m2 as a 90-min intravenous infusion, followed by FA 20 mg/m2 as an intravenous bolus, and 5-FU 500 mg/m2 over a 2-hour intravenous infusion on days 1 and 8. L-OHP was administered at 85 mg/m2 over 2 h on day 15, in combination with a FA 60 mg/m2 intravenous bolus and 5-FU 600 mg/m2 as a 2-hour intravenous infusion on days 15-16. The treatment was repeated every 4 weeks for a maximum of 9 cycles.. Twenty-five of 50 assessable patients achieved a complete (n=5) or partial (n=20) response, leading to a response rate of 50% (95% CI 35-64%). Eighteen (36%) patients showed stable disease. The median time to tumor progression was 10.3 months (95% CI 9.6-10.9 months). After a median follow-up of 16.4 months, the median survival was not reached. Grade 3 neutropenia (8%), grade 3 nausea/vomiting (6%) and grade 3 diarrhea (2%) were the major adverse events.. This alternating three-drug regimen is very well tolerated, manageable and effective in terms of activity and time to progression.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Diarrhea; Disease Progression; Drug Administration Schedule; Female; Fluorouracil; Follow-Up Studies; Humans; Infusions, Intravenous; Injections, Intravenous; Irinotecan; Leucovorin; Male; Middle Aged; Nausea; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Treatment Outcome; Vomiting

A randomized crossover study between 0.3 mg of ramosetron (RAM) combined with 8 mg of dexamethasone (DEX) and 0.3 mg of RAM combined with 12 mg of DEX was performed to investigate the prevention of nausea and vomiting due to chemotherapy including 60 mg/m2 or 70 mg/m2 of cisplatin (CDDP) in patients with advanced head and neck squamous cell carcinoma (HNSCC). Twenty-five patients the study consisted of who received chemotherapy with CDDP were enrolled in the present study between January 2001 and December 2002 at the Yokohama City University School of Medicine or Yokohama City University Medical Center. The antiemetic effectiveness in the group receiving 12 mg of DEX was not significantly superior to the group receiving 8 mg of DEX. It was suggested that the antiemetic therapy of RAM 0.3 mg plus DEX 8 mg was effective for the prevention of nausea and vomiting induced by CDDP in patients with advanced HNSCC.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carcinoma, Squamous Cell; Cisplatin; Cross-Over Studies; Dexamethasone; Drug Therapy, Combination; Female; Fluorouracil; Head and Neck Neoplasms; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Nausea; Vomiting, Anticipatory

This multicentre phase I/II study was designed to determine the maximum tolerated dose of irinotecan when combined with 5-fluorouracil and folinic acid according to the Mayo Clinic schedule and to evaluate the activity of this combination as first-line therapy in patients with advanced colorectal cancer.. Sixty-three patients received irinotecan (250 or 300 mg/m2, 30- to 90-minute intravenous infusion on day 1), immediately followed by folinic acid (20 mg/m2/day) and 5-fluorouracil (425 mg/m2, 15-minute bolus infusion) days 1 to 5, every four weeks.. Diarrhoea was dose limiting at 300 mg/m2 irinotecan in combination with 5-fluorouracil and folinic acid, and this was determined to be the maximum tolerated dose. Grade 3-4 neutropenia was the most frequently reported toxicity. The recommended dose of irinotecan for the phase II part of the study was 250 mg/m2. The response rate for the evaluable patient population was 36% (13/36), and 44% (16 patients) had stable disease (including 19% of minor response). For the intention-to-treat population, the response rate was 29% (14/49) and 35% (17 patients) stable disease (including 14% of minor response). The median time to progression was 7.0 months and the median survival was 12.0 months. Grade 3-4 non-haematological drug-related toxicities included delayed diarrhoea, stomatitis, fatigue, and nausea/vomiting. There were three deaths due to septic shock that were possibly or probably treatment-related.. This regimen of irinotecan in combination with the Mayo Clinic schedule of bolus 5-fluorouracil/folinic acid every four weeks showed activity as first-line therapy in patients with advanced colorectal cancer. In keeping with other published results of studies using bolus 5-fluorouracil combined with irinotecan, the use of this regimen is limited by a relatively high rate of grade 3-4 neutropenia, and the combination of irinotecan and infusional 5-fluorouracil / folinic acid should remain the regimen of first choice.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Diarrhea; Fatigue; Female; Fluorouracil; Hematologic Diseases; Humans; Irinotecan; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Nausea; Shock, Septic; Stomatitis; Survival Rate

Combination therapy of irinotecan, folinic acid (FA) and 5-fluorouracil (5-FU) has been proven to be highly effective for the treatment of metastatic colorectal cancer. However, in light of safety and efficacy concerns, the best combination regimen for first-line therapy still needs to be defined. The current study reports on the bimonthly FOLFIRI protocol consisting of irinotecan with continuous FA/5-FU in five German outpatient clinics, with emphasis on the safety and efficiency, quality of life, management of delayed diarrhea, and secondary resection of regressive liver metastases.. A total of 35 patients were treated for metastatic colorectal cancer. All patients received first-line treatment according to the FOLFIRI regimen, consisting of irinotecan (180 mg/m2), L-FA (200 mg/m2) and 5-FU bolus (400 mg/m2) on day 1, followed by a 46-h continuous infusion 5-FU (2400 mg/m2). One cycle contained three fortnightly administrations. Staging was performed after 2 cycles. Dosage was reduced at any time if toxicity NCI CTC grade III/IV was observed. Chemotherapy was administered only to diarrhea-free patients.. The FOLFIRI regimen was generally well tolerated. It was postponed for one-week in 51 of 415 applications (12.3%). Dose reduction was necessary in ten patients. Grade III/IV toxicity was rare, with diarrhea (14%), nausea/vomiting (12%), leucopenia (3%), neutropenia (9%) and mucositis (3%). The overall response rate was 31% (4 CR and 7 PR), with disease control in 74%. After primary chemotherapy, resection of liver metastases was achieved in three patients. In one patient, the CR was confirmed pathologically. Median progression-free and overall survival were seven and 17 months, respectively.. The FOLFIRI regimen proved to be safe and efficient. Outpatient treatment was well tolerated. Since downstaging was possible, combinations of irinotecan and continuous FA/5-FU should further be investigated in neoadjuvant protocols.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Colorectal Neoplasms; Diarrhea; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil; Hematologic Diseases; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Male; Middle Aged; Nausea; Quality of Life; Remission Induction; Treatment Outcome

Advanced pancreatic cancer has limited treatment options. 5-fluorouracil (5-FU) is frequently used in the treatment of pancreatic cancer. Preclinical studies suggest synergism between trimetrexate (TMTX),5-FU, and leucovorin (NFL).. We conducted a phase II trial to evaluate the activity and safety of NFL in pancreatic cancer.. Eligible patients (n = 21) with untreated advanced pancreatic cancer were treated with 110 mg/m2 intravenous (IV) THTX on day 1 and 200 mg/m2 IV leucovorin prior to 500 mg/m2 IV 5-FU on day 2. Oral leucovorin (15 mg every 6 h for seven doses) started intravenous 24 h later.. Treatment was administered for 6 wk followed by a 2-wk rest period. Response was evaluated every 8 wk. All patients were evaluable for response and toxicity. Most patients (80%) had distant metastases. Forty-five cycles of chemotherapy were administered. The most common serious toxicities were Grade 3 diarrhea (23.8%) and nausea and vomiting (14.2%). The response rate was 4.1% (95% CI, 0-23%), median survival was 6.8 mo, and 1-yr survival was 19%.. Treatment with NFL is well-tolerated in patients with advanced pancreatic cancer. The median survival and 1-yr survival in these patients with poor prognosis compares favorably with other treatment options.

Topics: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Nausea; Pancreatic Neoplasms; Survival Analysis; Treatment Outcome; Trimetrexate; Vomiting

To assess the activity and safety of combined folinic acid (FA), 5-fluorouracil (5-FU) and mitomycin C (MMC) in metastatic breast cancer patients previously treated with at least two chemotherapy regimens.. A total of 104 consecutive patients were enrolled for treatment with FA 100 mg/m(2) plus 5-FU 400 mg/m(2) i.v. on days 1-5, and MMC 3 mg/m(2) on days 3-5 (FFM). The cycles were repeated every 21 days until progression, severe toxicity or patient refusal.. Of the 104 patients, 96 were evaluable for response and toxicity. The overall response rate was 43% (95% confidence interval 32.8-53.2%); 40 patients achieved stable disease (42%) and 15 progressed (15%). In a retrospectively defined subgroup of patients with clinical resistance to taxanes (12 patients) or anthracyclines (14 patients), the response rate was 42%. The median time to progression was 8 months (3-18 months), and the median overall survival was 10.5+ months (2-36 months). The most common treatment-related adverse events were stomatitis, neutropenia, nausea/vomiting and diarrhea. Stomatitis, neutropenia and thrombocytopenia were the only grade 4 treatment-related adverse events, and occurred in no more than 3% of patients.. The tested FFM regimen seems to offer a valid option for patients with metastatic breast cancer who have been pretreated with two or more chemotherapeutic lines or who have failed on regimens containing anthracyclines or taxanes.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Disease Progression; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Mitomycin; Nausea; Neoplasm Metastasis; Neutropenia; Quality of Life; Stomatitis; Survival Rate; Treatment Outcome

In vitro, methotrexate (MTX) is the best modulator for bolus 5-fluorouracil (5FU), whereas folinic acid (FA) is the best for continuous infusion. We evaluated the effect of 5FU modulated by both MTX (bolus administration) and FA (continuous infusion) as second-line treatment of patients with metastatic colorectal cancer.. Entry criteria were: at least one 5FU-based chemotherapy regimen as first-line treatment for metastatic disease, or progression within twelve months after 5FU-containing adjuvant therapy. Treatment schedule: MTX 200 mg/m2 i.v. days 1 and 15; 5FU 600 mg/m2 i.v. bolus, days 2 and 16; 5FU 200 mg/m2 i.v. continuous infusion for 21 days, starting on day 29; FA 20 mg/m2 i.v. bolus weekly during the three weeks of 5FU infusion. Cycles were repeated every 56 days. The primary end-point was tumour control rate, including partial responses and stabilizations.. 34/35 patients enrolled were evaluable for response. Five (14.7%) had a partial response, 13 (38.2%) disease stabilization, and 16 (47.1%) progressed; tumour control rate was 52.9%. Median TTP was 5.8 months (95% CI 4.03-7.83); 29 patients had died. Median OAS was 15.9 months (95% CI 8.8-21.9). Toxicity was mild.. The regimen constituted by 5FU modulated by MTX (bolus administration) and FA (continuous infusion) is active as second-line treatment of metastatic colorectal cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Diarrhea; Disease Progression; Fluorouracil; Follow-Up Studies; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Methotrexate; Middle Aged; Nausea; Neoplasm Staging; Survival Rate; Treatment Outcome; Vomiting

Biochemical modulation of 5-fluorouracil (5-FU) has been verified the evidence of significant improvement of survival and quality of life in patients with advanced colorectal carcinoma. We investigated the therapeutic and adverse drug reaction of intensive chemotherapy using cisplatin (CDDP), 5-FU and dl-leucovorin (LV) (PFL-therapy), which may be producing dual biochemical modulation effect of 5-FU for advanced colorectal carcinoma. Administration schedule was 13 mg/m2 of CDDP, 300 mg/m2 of 5-FU, and 30 mg/body of dl-LV for 5 consecutive days. This regimen was repeated at 3-week intervals in hospital. Sixteen patients were enrolled in this study, most of whom had a history of previous chemotherapy as adjuvant treatment, and the response rate was 25%, with four patients having "partial response" and eight "no change". In respect to performance status, 46% of patients who completed the protocol were markedly improved in spite of their poor performance status before treatment. Moreover, when patients were classified into two groups based on changes of the serum level of CEA, "responder in CEA level" showed better prognosis than "non-responder in CEA level". Major toxicities were nausea, hyperglycemia and neutropenia. Three patients experienced Grade 4 hematological side effect, but these complications resolved quickly in all patients except for one patient. PFL-therapy is effective for advanced colorectal cancer with large tumor burden and showed the same prognostic result as the American and European trials in spite of smaller number of treatment cycles and a history of previous chemotherapy. We will be able to demonstrate the usefulness of this regimen for Japanese patients with advanced colorectal cancers after adding new cases to the present report.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoembryonic Antigen; Cisplatin; Colorectal Neoplasms; Diarrhea; Drug Administration Schedule; Female; Fluorouracil; Humans; Karnofsky Performance Status; Leucovorin; Leukopenia; Male; Middle Aged; Nausea; Skin Diseases; Stomatitis; Survival Rate; Thrombocytopenia; Treatment Outcome; Vomiting

We evaluated the efficacy and safety of ondansetron hydrochloride (OND) on nausea and vomiting during repeated courses of CHOP or ACOMP-B therapy in patients with malignant lymphoma. The impact of the prognosis announcement on the anti-emetic effect and chemotherapy-associated adverse events was also investigated. Forty-two subjects with malignant lymphoma who underwent CHOP or ACOMP-B therapy including cyclophosphamide 600 mg/m2 and adriamycin 40 mg/m2 were investigated for a maximum of 6 courses. For acute nausea and vomiting, ondansetron was injected intravenously before the start of chemotherapy on the first day of each course of chemotherapy. For delayed emesis, ondansetron was administered orally for 4 days from the following day. The efficacy on acute nausea and vomiting was found to be 95.0% (1st course), 95.0% (2nd course), 90.9% (3rd course), 88.2% (4th course), 92.3% (5th course) and 91.7% (6th course), respectively. A high efficacy of > or = 85% was also obtained for delayed nausea and vomiting on each day. Though the adverse event of elevated GPT value developed in one subject. It was mild and resolved. No difference in efficacy was seen with or without announcement of prognosis to patients. Following the investigation on antiemetic effect, patient perception of chemotherapy-induced adverse events was evaluated. The most common event was hair loss, followed by taste abnormality and numbness and hyposthesia of the tips of the fingers. The incidence of nausea and vomiting was the 4th and 5th most common, which are less frequent than in the report of Coates in 1983. In conclusion, ondansetron is considered clinically useful with stable anti-emetic effect on both acute and delayed nausea and vomiting over repeated courses of chemotherapy, without any significant safety problem.

Topics: Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Nausea; Ondansetron; Prednisolone; Prednisone; Prognosis; Vincristine; Vomiting, Anticipatory

The present study was designed to determine the maximum tolerated dose (MTD), toxicity profile, pharmacokinetics (PKs), and antitumor activity of the protein kinase C-alpha antisense oligonucleotide ISIS 3521 (ISIS Pharmaceuticals, Inc., Carlsbad, CA) when administered in combination with 5-fluorouracil (5-FU) and leucovorin (LV). Patients with refractory solid tumors received ISIS 3521 as a 21-day continuous infusion administered simultaneously with 5-FU and LV given daily for 5 days repeated every 4-5 weeks (one cycle). 5-FU and ISIS 3521 PK analysis were performed on samples taken during the first cycle in all patients. Fifteen patients received ISIS 3521 at one of three dose levels: (a) 1.0 (n = 3 patients); (b) 1.5 (n = 3 patients); and (c) 2.0 (n = 9 patients) mg/kg/day. All patients simultaneously received 5-FU (425 mg/m(2)/day) and LV (20 mg/m(2)/day) for 5 consecutive days. Grade 1-2 toxicities included alopecia, fatigue, mucositis, diarrhea, anorexia, nausea/vomiting, and tumor pain. One patient had grade 3 chest pain considered to be related to 5-FU therapy, another patient had dose-limiting grade 3 mucositis resolving in <7 days, and one patient with a history of gastritis had an acute upper gastrointestinal bleed thought to be 5-FU-induced toxicity. Five patients developed cycle 1 grade 4 neutropenia, which resolved without colony-stimulating factors before the next treatment cycle. There were no effects on prothrombin time and activated partial thromboplastin time. A clinically defined MTD was not reached. The character and severity of these toxicities do not seem to be dose related, and, as such, there was no classical dose-limiting toxicity defining the MTD. ISIS 3521 PKs in the presence of 5-FU was consistent with those reported previously. 5-FU PK parameters were also similar in the presence or absence of ISIS 3521. Six of 14 patients ( approximately 43%) across all dose cohorts had an improvement in measurable tumor response ranging from minor reduction in tumor size (4 patients) to objective partial response (>50% reduction in tumor size, 2 patients). ISIS 3521 is tolerable at its recommended single-agent dose when given with 5-FU and LV. There is no apparent PK interaction between ISIS 3521 and 5-FU and LV. Antitumor activity was observed with the combination; however, it is uncertain whether clinical activity is a result of enhanced drug interaction. Our study warrants further exploration of efficacy in a Phase II and/or Phase III cl

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Diarrhea; DNA, Antisense; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fatigue; Female; Fluorouracil; Humans; Isoenzymes; Leucovorin; Male; Middle Aged; Nausea; Neoplasms; Neutropenia; Oligonucleotides; Protein Kinase C; Protein Kinase C-alpha; Thionucleotides; Thrombocytopenia; Treatment Outcome; Vomiting

Topics: Administration, Oral; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Diarrhea; Drug Combinations; Fluorouracil; Humans; Leucovorin; Nausea; Survival Rate; Tegafur; Time Factors; Uracil

To compare the response rate, efficacy parameters, and toxicity profile of oral capecitabine with bolus intravenous (IV) fluorouracil plus leucovorin (5-FU/LV) as first-line treatment in patients with metastatic colorectal cancer.. We prospectively randomized 605 patients to treatment with oral capecitabine for 14 days every 3 weeks or 5-FU/LV by rapid IV injection daily for 5 days in 4-week cycles.. The overall objective tumor response rate among all randomized patients was significantly higher in the capecitabine group (24.8%) than in the 5-FU/LV group (15.5%; P =.005). In the capecitabine and 5-FU/LV groups, median times to disease progression were 4.3 and 4.7 months (log-rank P =.72), median times to treatment failure were 4.1 and 3.1 months (P =.19), and median overall survival times were 12.5 and 13.3 months (P =.974), respectively. Capecitabine, compared with bolus 5-FU/LV treatment, produced a significantly lower incidence (P <.0002) of diarrhea, stomatitis, nausea, and alopecia. Patients treated with capecitabine also displayed lower incidences of grade 3/4 stomatitis and grade 3/4 neutropenia (P <.0001) leading to significantly less neutropenic fever/sepsis. Grade 3 hand-foot syndrome (P <.00001) and grade 3/4 hyperbilirubinemia were the only toxicities more frequently associated with capecitabine than with 5-FU/LV treatment.. Oral capecitabine was more active than 5-FU/LV in the induction of objective tumor responses. Time to disease progression and survival were at least equivalent for capecitabine compared with the 5-FU/LV arm. Capecitabine also demonstrated clinically meaningful benefits over bolus 5-FU/LV in terms of tolerability.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Alopecia; Antimetabolites, Antineoplastic; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Diarrhea; Disease Progression; Female; Fluorouracil; Humans; Injections, Intravenous; Leucovorin; Male; Middle Aged; Nausea; Stomatitis; Survival Analysis; Treatment Outcome

We have reported that an alternating regimen of bolus and continuous infusion 5-fluorouracil (FU) was superior to bolus FU in terms of response rate and progression-free survival in advanced colorectal cancer. Biochemical modulation was an essential part of this regimen and it was selective for the schedule of FU administration: bolus FU was in fact modulated by methotrexate (MTX) while continuous infusion FU was potentiated by 6-s-leucovorin (LV). Considering the low cost and the favourable report on the activity of mitomycin C (mito) added to CI FU, we have incorporated this agent in the infusional part of our treatment programme. 105 patients with untreated, advanced, measurable colorectal cancer were accrued from 13 Italian centres and treated with the following regimen. 2 biweekly cycles of FU bolus (600 mg/m(2)), modulated by MTX (24 h earlier, 200 mg/m(2)) were alternated with a 3-week continuous infusion of FU (200 mg/m(2)daily), modulated by LV (20 mg/m(2)weekly bolus). Mito, 7 mg/m(2), was given on the first day of the infusional period. After a 1 week rest, the whole cycle (8 weeks) was repeated, if indicated. 5 complete and 34 partial responses were obtained (response rate, 37% on the intention to treat basis; 95% confidence limits, 28-46%). After a median follow-up time of 26 months, 37 patients are still alive. The median progression-free survival is 7.7 months with an overall survival of 18.8 months and a 2-year survival rate of 30%. The regimen was very well tolerated with fewer than 13% of patients experiencing WHO grade III-IV toxicity. These results are consistent with those obtained by our group in 3 previous trials of schedule specific biochemical modulation of FU. They also indicate a highly active, little toxic, inexpensive regimen of old drugs to be used (a) as an alternative to the more expensive combinations including CPT-11 or oxaliplatin or (b) as the basis for combination programmes with these agents.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Conjunctivitis; Diarrhea; Female; Fluorouracil; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Mitomycin; Mouth Mucosa; Nausea; Stomatitis; Survival Analysis; Treatment Outcome; Vomiting

5-fluorouracil (5-FU) clearly behaves as two different drugs according to the schedules for its administration. A weekly, 8-h 5-FU continuous infusion (CI) regimen may produce a dual effect, because it elicits both a high plasma 5-FU level and also a durable exposure to 5-FU, which may have the advantage of inhibiting both DNA synthesis and RNA activities. The plasma 5-FU level, however, cannot be monitored in most hospitals, so we initiated a pragmatic clinical trial with this weekly 8-h 5-FU Cl regimen and adjusted the drug's dose according to the detected toxicity.. The initial dose of 5-FU was 1200 mg/m2 and this was escalated by 200 mg/m2 weekly, provided that no evidence of significant (grade 2 or greater) toxicity became apparent. Twenty-six patients entered the study from June 1998 to March 1999.. The median dose of 5-FU delivered was 1600 mg/m2. The major symptoms precluding dose escalation were nausea and vomiting. Seven patients demonstrated a partial response (26.9%), 11 patients revealed stable disease (42.3%) and eight exhibited progressive disease (30.8%).. This weekly 8-h CI 5-FU protocol with the adjustment of dose according to toxicity was not able to achieve the same 5-FU dose and response rate as in previous studies with pharmacokinetic monitoring of 5-FU levels. However, with the concurrent administration of intensive anti-emetic premedication, it is still possible to achieve adequate plasma 5-FU levels by adjusting the 5-FU dose according to elicited toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Nausea; Rectal Neoplasms; Vomiting, Anticipatory

From July 1992 to May 1996, 16 patients with non-curative postoperative or recurrent colorectal carcinomas were treated with 5-fluorouracil (5-FU) plus leucovorin (LV) systemic chemotherapy. LV was given at a dose of 20 mg/m2/d immediately followed by 5-FU at 370 mg/m2/d. LV was given by rapid intravenous (i.v.) injection and 5-FU by rapid or drip i.v. for 5 consecutive days. Courses were repeated once every 4 weeks for two months and then once every 5 weeks. All patients took 3 or more courses. The toxicity was tolerable, but one patient needed hospitalization because of severe gastro-intestinal toxicity. We observed 3 PR cases, no CR and an overall response rate of 19%. The response duration was 6 to 8 months, averaging 7.3 months, and median survival was 12 months. It was possible to perform this chemotherapy on an outpatient basis, so we think this chemotherapy is superior to in-hospital chemotherapy considering the issue of quality of life. However, the response rate was low and its duration was short. We must investigate chemotherapy further with new and more powerful chemical modulations to increase the response rate and to prolong the response duration.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Colorectal Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Nausea; Survival Rate; Vomiting, Anticipatory

To evaluate the toxicity and efficacy of a 4-day regimen of docetaxel, cisplatin, fluorouracil, and leucovorin (TPFL4) in patients with locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN).. Thirty previously untreated patients with stage III or IV SCCHN and Eastern Cooperative Oncology Group functional status of 2 or less were treated with TPFL4. Postchemotherapy support included prophylactic growth factors and antibiotics. Patients who achieved a complete response (CR) or partial response (PR) to three cycles of TPFL4 received definitive twice-daily radiation therapy. The primary end points were toxicity and response to TPFL4.. Eighty-five cycles were administered to 30 patients. The major acute toxicities to TPFL4 were mucositis and nausea. One patient died of neutropenic sepsis during therapy. Additional major toxicities were neutropenia, anorexia, nephropathy, neuropathy, and diarrhea. Fourteen percent of all cycles were associated with hospitalization for toxicity. The overall clinical response rate to TPFL4 was 93%, with 63% CRs and 30% PRs. Primary tumor site clinical and pathologic response rates were 93% and 68%, respectively.. TPFL4 has an acceptable toxicity profile in good-performance-status patients. Modification of the 5-day TPFL regimen (TPFL5: shorter chemotherapy infusion time, earlier intervention with growth factors and antibiotics) led to fewer episodes of febrile neutropenia and hospitalization. Response rates to TPFL justify further evaluation of combinations of these agents in the context of formal clinical trials.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Dose-Response Relationship, Drug; Fluorouracil; Head and Neck Neoplasms; Humans; Leucovorin; Middle Aged; Mouth Mucosa; Nausea; Paclitaxel; Stomatitis; Taxoids

A Phase I study of UFT plus l-LV was conducted in 29 patients (pts) with G.I. cancer on a multicenter cooperative study. UFT and l-LV were given orally in two divided doses for 28 consecutive days, followed by a 14 day-rest period. UFT was fixed in three doses, 250, 313 and 375 mg/m2/day, and l-LV was increased in dose from 25 to 50 and to 100 mg/body/days. Dose-limiting toxicities were anorexia, diarrhea, and nausea/vomiting. The maximum tolerated dose of UFT was 375 mg/m2/day, and l-LV 25 mg/body/day. Severe myelotoxicity was not observed. There were three responders (PR) out of 21 pts with measurable disease at UFT doses of 313 mg/m2/day and l-LV 50 and 100 mg/body/day. Responses observed were abdominal mass (rectal ca), liver metastasis (pancreas ca) and metastasis of liver and lymph-node (gastric ca). As a result of pharmacokinetics, plasma concentrations of 5-methyl-THF were maintained > 1.0 microM for over 5 hours that was considered to have a modulating effect on the plasma concentration. In doses of 50 mg and 100 mg/body/day of l-LV. No accumulations in plasma were observed in patient treated in 28 days by l-LV/UFT therapy. It was suggested UFT and l-LV did not interfere with each other's absorption. A Phase II study is recommended, with doses of 313 mg/m2/day of UFT and 50 or 100 mg/body/day of l-LV.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Combinations; Female; Gastrointestinal Neoplasms; Humans; Leucovorin; Male; Middle Aged; Nausea; Stomach Neoplasms; Tegafur; Uracil; Vomiting

Chemotherapy of neuroendocrine tumors must be improved. The most widely used regimen, which combines streptozotocin with fluorouracil, commonly obtains poor results. The best response rate that has been reported for carcinoid tumors is 33%. From July 1991 through September 1994, 18 patients who had advanced neuroendocrine tumors-including nine carcinoid tumors, seven neuroendocrine tumors of unknown primary site, one insulinoma, and one paraganglioma-were treated with a regimen of dacarbazine, 400 mg/m2/day, plus fluorouracil, 1 g/m2/day, with leucovorin, 200 mg/m2/day, for 2 days every 21 days (DTIC-LVFU2 protocol). The results were assessed according to the World Health Organization criteria of toxicity and response. Toxicity was moderate. The most severe side effects were grade 3 vomiting in two patients, grade 3 leukopenia in three patients, and grade 3 mucositis in one patient. The overall response rate was 27%, with only one partial response for carcinoid tumors but one complete and three partial responses for the other tumor types. Efficacy was insufficient in patients who had carcinoid tumors but the combination of dacarbazine with fluorouracil and leucovorin could be an effective regimen for the treatment of neuroendocrine tumors of unknown primary site.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoid Tumor; Dacarbazine; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Nausea; Neoplasms, Unknown Primary; Neuroendocrine Tumors; Survival Rate

To evaluate toxicity and efficacy of chemotherapy in elderly patients (> or = 65 years of age) with advanced colorectal cancer, data from two consecutive trials conducted between 1984 and 1995 at the National Institute for Cancer Research were analysed comparing the results of treatment in those 65 years of age or older and in those younger than 65 years. Of 215 patients recruited, 82 elderly patients (median age 70 years, median performance status 1) received one of the following regimens based on 5-fluorouracil (5-FU): (1) weekly 5-FU 600 mg/m2 i.v. bolus (30 patients); (2) weekly 5-FU 600 mg/m bolus plus leucovorin (LV) 500 mg/m2 2-h i.v. infusion (28 patients); (3) Weekly 5-FU 2600 mg/m2 24-h continuous i.v. infusion plus LV 100 mg 4-h i.v. infusion and 50 mg orally every 4 h for five doses (24 patients). Overall, 1071 chemotherapy cycles were administered with a median number of 12 courses per patient. The main side effects were diarrhoea, observed in 38% of patients, stomatitis in 24% of patients and hand-foot syndrome in 13% of patients, and haematological toxicity affected only 15% of patients. No patient suffered grade IV toxicity. In three patients chemotherapy was discontinued because of toxicity (two patients suffered grade III diarrhoea, one patient grade III hand-foot syndrome). No significant difference in toxicity was evident between patients older than or younger than 65 years. Analysis of median dose intensity demonstrated no difference between the two groups. Overall objective response was observed in 18% (95% confidence limits 11-29) of elderly patients (15/82) in comparison with 23% (95% CL 17-32) of patients < 65 years of age (31/133 pts). In conclusion, chemotherapy in elderly patients with advanced colorectal cancer is a safe and effective treatment with acceptable toxicity and comparable objective response rates.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Diarrhea; Dose-Response Relationship, Drug; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Nausea; Quality of Life; Retrospective Studies; Stomatitis

Uracil and tegafur in a 4:1 molar concentration ratio (UFT; Bristol-Myers Squibb, Wallingford, CT) has broad anti-tumor activity for cancers arising from the gastrointestinal tract. However, there are no published data regarding the efficacy of leucovorin-modulated UFT in patients with pancreatic cancer. The objective of this trial was to determine the activity and evaluate the toxicity of UFT plus oral calcium leucovorin in patients with advanced pancreatic adenocarcinoma.. Fourteen patients with advanced measurable adenocarcinoma of the pancreas were enrolled onto the trial. Patients received 300 mg/m2/d UFT plus 90 mg/d leucovorin administered orally in divided doses every eight hours for 28 days repeated every 35 days. Objective tumor response was evaluated after two courses of therapy.. Fourteen patients were evaluable for response and toxicity. No objective responses were seen. The median (range) time to progression and survival were 14 (1.6-37), and 15 (1.9-62) weeks, respectively. Toxicity was mild with severe (grade 3 or 4) hyperbilirubinemia, pain, diarrhea, transaminitis, venous thrombus, weakness, renal failure, confusion, and edema/ascites seen in three (21%), one (7%), two (14%), one (7%), one (7%), one (7%), one (7%), one (7%), and two (14%) patients, respectively.. In the 14 patients evaluable, UFT 300 mg/m2/d plus oral leucovorin 90 mg/d administered for 28 days did not demonstrate anti-tumor activity against advanced pancreatic adenocarcinoma; however, this oral regimen was well tolerated and devoid of neutropenia, significant oral mucositis or diarrhea.

Topics: Adenocarcinoma; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Leucovorin; Male; Nausea; Pancreatic Neoplasms; Tegafur; Treatment Outcome; Uracil

The oral fluoropyrimidines have proved to be active in colorectal cancer in Japan and, recently, in the United States and Europe. Continuous oral administration simulates protracted fluorouracil (5-FU) continuous intravenous infusion. The purpose of this trial was to evaluate the tolerability and potential advantages of oral treatment for colorectal cancer in the elderly. The main inclusion criterion was age over 72 years. Patients were treated with UFT (tegafur plus uracil) 400 mg/24 hours (fixed doses) continuously plus folinic acid 45 mg/24 hours until toxicity. If grade 3 or 4 toxicity appeared, treatment was stopped until recovery. From September 1994 to November 1996, 126 patients were included. For the analysis in November 1996, 77 patients were evaluable for response, toxicity, and survival. The patients, including 34 women and 43 men, had a median age of 74 years (range, 72 to 82 years of age). The Karnofsky performance status was 60% to 80% for 41 patients and 90% to 100% for 36 patients. Liver metastasis was present in 48% of the cases, and 42% were locoregional and peritoneal. Toxicity was mild, with only one patient having grade 3 thrombocytopenia, 11 (14%) grade 3 or 4 nausea/vomiting, seven (9%) grade 3 or 4 diarrhea, and one grade 3 mucositis. Four patients (5%) had complete responses and nine (11.6%) partial responses, for an objective response rate of 16.9% (95% confidence interval, 9% to 27%). Twenty-two patients (28.6%) showed no change. The number of patients in whom disease did not progress (ie, patients with complete plus partial responses plus those with stable disease) was 35 (45.4%) (95% confidence interval, 34% to 57%). With a maximum follow-up of 24 months, the median actuarial survival is 14.4 months. The number without disease progression and the median survival in this preliminary analysis suggests that this schedule is a moderately effective, comfortable, treatment with only mild toxicity, that can be recommended for use in the elderly, and it warrants further study.

Topics: Aged; Aged, 80 and over; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Diarrhea; Drug Combinations; Drug Therapy, Combination; Female; Humans; Leucovorin; Leukopenia; Male; Nausea; Survival Analysis; Tegafur; Treatment Outcome; Uracil

During the 1990s, one in nine women in the western world will be diagnosed with breast cancer, and more than 58,000 will die of the disease each year in Europe alone. Recent changes in the primary therapy of operable breast cancer have not altered patient prognosis. Adjuvant therapy delays systemic recurrence and improves survival for only a fairly selected fraction of these patients. Therapy for metastatic breast cancer has not improved significantly in recent years. While combination chemotherapy may prolong survival in selected patients, few if any achieve cure. Standard chemotherapy regimens used to treat metastatic breast cancer, such as CMF (cyclophosphamide/methotrexate/fluorouracil), FAC (5-FU/Adriamycin/cyclophosphamide), and FEC (5-FU/epirubicin/cyclophosphamide), were developed over a decade ago. Current efforts to improve therapeutic efficacy have concentrated on decreasing drug toxicity and increasing drug doses (e.g., high-dose chemotherapy with peripheral stem cell support). An important alternative to increasing therapeutic efficacy by such approaches is altering the administration schedules of well-known chemotherapeutic agents and introducing active new cytotoxic agents. One of the most frequently used cytotoxic drugs, 5-FU has documented activity in a variety of malignancies, most notably in breast cancer and gastrointestinal tract cancers. However, despite broad clinical experience, our knowledge of mechanisms of resistance in relation to various 5-FU schedules is limited. In vitro data and clinical experience show that resistance to one schedule of 5-FU can be overcome by using an alternative schedule, most often a protracted infusion.

Topics: Adult; Aged; Anemia; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Diarrhea; Drug Therapy, Combination; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Nausea; Neutropenia; Paclitaxel; Thrombocytopenia; Treatment Outcome

Gastric cancer is the most chemosensitive adenocarcinoma among digestive neoplasms. A few years ago, we performed a phase II trial with the FLEP regimen, in which fluorouracil (5-FU) and leucovorin are combined with etoposide and cisplatin (Platinol). This regimen resulted in a 39% response rate and high toxicity. Then we used the combination UFT (tegafur and uracil)/leucovorin/etoposide: UFT 390 mg/m2/day orally on days 1 to 14; leucovorin 500 mg/m2 i.v. day 1, and 15 mg/12 h orally on days 2 to 14; and etoposide 100 mg/m2 i.v. on day 1 and then 200 mg/m2/day orally on days 2 and 3. Forty-six patients received a median of five courses. Five patients (11%) achieved a complete response and 12 (26%) a partial response, for an overall response rate of 37%. The response rate was 50% in patients with an Eastern Cooperative Oncology Group performance status of 0 to 1. Grades 3 to 4 toxicities appeared as follow: 17% of patients had diarrhea, 11% had nausea/vomiting, and 13% of patients had anemia. One patient died of neutropenia and sepsis. The median survival time was 9 months. In summary, UFT/leucovorin/etoposide is effective and moderately toxic in patients with advanced gastric cancer. A new trial with UFT/leucovorin/epirubicin is ongoing.

Topics: Anemia; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Drug Combinations; Etoposide; Female; Forecasting; Humans; Leucovorin; Male; Nausea; Stomach Neoplasms; Survival Rate; Tegafur; Uracil

Thirty-nine patients with locally advanced or metastatic gastric carcinoma received oral UFT (tegafur and uracil) plus leucovorin. Treatment consisted of UFT 360 mg/m2/day plus leucovorin 25 mg/m2/day, given orally in divided daily doses for 21 days followed by a 7-day rest period. The median age of the patients was 64 years, and the median World Health Organization performance status was 2. Patients received a median of two courses of treatment (range, 1 to 25). Among 37 evaluable patients, two patients achieved a complete response, and eight had partial responses, for an overall response rate of 27% (95% confidence interval, 15.4% to 42.9%). Stable disease was reported in 12 patients (32%) and another 15 showed disease progression. The median duration of response was 30 weeks, and the median duration of survival was also 30 weeks (range, 8 to 111). All patients were evaluable for toxicity. Significant toxicity (World Health Organization grade 3 or 4) included diarrhea in seven patients (18%), oral mucositis in six (15%), and nausea/vomiting in six patients. We conclude that oral UFT plus leucovorin, an outpatient regimen, has favorable activity in patients with gastric carcinoma and has tolerable toxicities.

Topics: Adult; Aged; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Diarrhea; Drug Combinations; Female; Follow-Up Studies; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Nausea; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome; Uracil

We performed a phase II study to assess the efficacy and toxicity of the cisplatin-UFT-leucovorin (LV) combination in patients with advanced non-small-cell lung cancer (NSCLC). Twenty-five patients with measurable disease who had not received prior chemotherapy were entered into the trial. The therapeutic regimen consisted of cisplatin 90 mg/m(2) and i.v. LV 500 mg/m(2) on day 1, followed by oral UFT 390 mg/m(2)/day (in two doses on days 1 through 14. Patients also received oral LV 15 mg/12 h on days 2 through 14. Seventeen patients required reduced doses of UFT (200 mg/m(2) due to toxicity. Courses were repeated every 28 days for a minimum of three per patient. Three of 25 patients (12%) achieved a partial response (95% CI: 2.6 to 32.2%), two with 390 mg/m(2)/day and one with 200 mg/m(2)/day of UFT. The main side effects were hematological and gastrointestinal. In the courses including 390 mg/m(2)/day of UFT, grade 3-4 toxicity was leucopenia in 18% of the courses, nausea/vomiting in 27%, and diarrhea and epigastralgia in 13% each. Grade 3-4 toxicities for 200 mg/m(2)/day of UFT were leucopenia 2%, nausea/vomiting 9% and diarrhea 7%. In conclusion, this regimen cannot be recommend for the treatment of advanced NSCLC due to its low response rate and high toxicity.

Topics: Abdominal Pain; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Diarrhea; Drug Administration Schedule; Female; Humans; Leucovorin; Leukopenia; Lung Neoplasms; Male; Middle Aged; Nausea; Remission Induction; Tegafur; Vomiting

Both the biochemical modulation and the continuous administration of 5-fluorouracil (5-FU) have achieved promising results in patients with gastric carcinoma. Conversely, several studies on gastric carcinoma have demonstrated that the combination of etoposide (VP-16), leucovorin (LV), and 5-FU (ELF) is efficacious and moderately toxic. UFT is a combination of uracil and tegafur (ftorafur) in a 4:1 molar ratio. It can be administered orally for several weeks, thus stimulating the effects of a continuous infusion of 5-FU. Its combination with LV increased the efficacy of UFT. We conducted a Phase II study on patients with gastric carcinoma using the combination VP-16-LV-UFT. This combination is administered mainly orally (p.o) and could yield a good response rate and low toxicity.. Forty-six patients with bidimensionally measurable disease were entered into the study. Patients received VP-16 100 mg/m2 IV on Day 1 and 200 mg/ m2 p.o. on Days 2 and 3; LV 500 mg/m2 administered intravenously (i.v.) on Day 1, followed by p.o. LV 15 mg every twelve hours on Days 2 to 14. Patients also received UFT p.o. 390 mg/m2/day on Days 1 to 14. Treatment was repeated every 28 days for a minimum of 3 courses per patient. All courses were given on an outpatient basis.. Four patients (9%) had a complete response, and 12 a partial response (26%) for an overall response rate of 35% (95% confidence interval: 22-51%). The median duration of response was 10 months. The median overall survival was 9 months. The main side effects were gastrointestinal. Grade 3 to 4 toxicity was encountered as follows: diarrhea in 17% of the patients, nausea/vomiting in 11%, anemia in 13%, mucositis and leukopenia in 4% each, and thrombocytopenia in 2%. One patient died of sepsis and neutropenia.. VP-16-LV-UFT has an activity comparable to that of other schemes and a low incidence of side effects. Furthermore, since it is administered mainly orally, hospitalization is avoided, which makes this scheme suitable for patients with advanced gastric carcinoma.

Topics: Administration, Oral; Adult; Aged; Ambulatory Care; Anemia; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Diarrhea; Drug Administration Schedule; Etoposide; Fluorouracil; Humans; Injections, Intravenous; Leucovorin; Middle Aged; Nausea; Remission Induction; Stomach Neoplasms; Survival Rate; Tegafur; Vomiting

A crossover clinical trial between granisetron alone and granisetron combined with methylprednisolone (MPL) was undertaken for the prevention of nausea and vomiting during chemotherapy, including cisplatin, in 12 patients with advanced primary and metastatic lung cancer. The antiemetic effect was obtained in 91.7% (11/12 cases) of patients receiving granisetron alone compared to 100% (12/12 cases) of patients receiving the combination of granisetron plus MPL. Complete control of anorexia was achieved in 91.6% (11/12 cases) of patients receiving the combination compared to 58.3% (7/12 cases) of patients receiving granisetron alone. Moreover there was a significant improvement of delayed clinical symptoms including nausea, vomiting, and anorexia in the patients receiving the combination of granisetron plus MPL. Our data suggest that the antiemetic effect of the combination of granisetron plus MPL is superior to granisetron alone in patients receiving cancer chemotherapy.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cross-Over Studies; Drug Therapy, Combination; Female; Fluorouracil; Granisetron; Humans; Leucovorin; Lung Neoplasms; Male; Methylprednisolone; Middle Aged; Nausea; Vomiting

Cisplatin (P) and 5-fluorouracil (5FU) have demonstrated activity for the treatment of squamous cell carcinoma of the esophagus. Previous studies have shown that leucovorin (L) may potentiate the antitumoral activity of 5FU, so we tested the combination P-5FU-L in 31 patients with inoperable squamous cell esophageal carcinoma. Chemotherapy consisted of P 20 mg/m2 in 4 h, followed by L 200 mg/m2 in 2 h and 5FU 600 mg/m2 in 18 h. This schedule was repeated for 5 days every 4 weeks. The treatment plan included three courses of chemotherapy followed by radiotherapy. The overall response rate was 58% (95% CI = 39-76%), with one complete remission (3%), and 61% of patients reported an improvement in dysphagia. Gastrointestinal toxicity was the main side effect: grade 3-4 mucositis appeared in 19% of patients, grade 3-4 nausea/vomiting in 13%, and grade 3-4 diarrhea in 6.5%. There was one toxic death caused by neutropenia and sepsis. Nineteen patients received local radiotherapy after chemotherapy, which increased the overall response rate to 63% (5% complete responses). Dysphagia improved in 75% of them. The median survival for all patients was 11 months. This study shows that sequential therapy with P-5FU-L and radiotherapy achieves a high response rate as well as adequate symptomatic relief in patients with inoperable esophageal cancer. The results justify further evaluation of P-5FU-L in patients with earlier-stage disease.

Topics: Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Deglutition Disorders; Diarrhea; Drug Administration Schedule; Drug Synergism; Enzyme Inhibitors; Esophageal Neoplasms; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Mucous Membrane; Nausea; Radiotherapy, Adjuvant; Remission Induction; Survival Rate; Thymidylate Synthase; Vomiting

A multicentral cooperative study was conducted to evaluate the clinical efficacy and toxicity of l-Leucovorin (l-LV) and 5-fluorouracil (5-FU) in advanced colorectal cancer. The administration schedule was a two-hour intravenous infusion of l-LV (250 mg/m2) and an intravenous bolus injection of 5-FU (600 mg/m2), given one hour after the beginning of the l-LV infusion. Sixty-four patients were treated weekly for six weeks followed by two-weeks rest, and then evaluated for response. Complete response and partial response were obtained in 21 patients (32.8%). The median survival time was 12.8 months. The most prominent side effects were anorexia (57.8%), nausea and vomiting (56.3%), diarrhea (48.4%) and myelosuppression such as leucopenia (54.7%), thrombocytopenia (18.8%) and decreased hemoglobin (40.6%). These side effects, however, were within permissible levels. Severe toxicity was prevented by discontinuance of the treatment. From the present study, l-LV and 5-FU combination therapy seems to be a very promising and useful treatment for patients with advanced colorectal carcinoma.

Topics: Adult; Aged; Anorexia; Colorectal Neoplasms; Diarrhea; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Leukopenia; Male; Middle Aged; Nausea; Remission Induction; Survival Rate

We previously reported positive results to Tegafur-Uracil (UFT) chemotherapy in a group of patients with advanced rectal cancer. We have continued the study and now report the effectiveness of UFT plus folinic acid (FA) in 52 patients with advanced rectal cancer. The therapeutic schedule was UFT, 600 mg/m2/day x 14 days p.o. + FA, 90 mg/m2/day x 14 days p.o. Fifty-two out of a total of 56 patients were evaluated for response and toxicity. A higher incidence of positive responses in patients without previous chemotherapy was appreciated. Twenty-one of the 52 evaluated patients showed a partial response (PR). Responses were strongly correlated with previous chemotherapy (14/20; 70% PR of cases without previous chemotherapy vs 7/32; 22% of cases with previous chemotherapy). All responding patients came forward with a median time to progression of 8.2 months (19.6 months for patients without previous chemotherapy vs 7.7 months for patients with previous chemotherapy, P < 0.01). We concluded that the UFT plus FA could be a treatment of choice for patients with advanced rectal cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Humans; Leucovorin; Leukopenia; Middle Aged; Nausea; Rectal Neoplasms; Survival Rate; Tegafur; Uracil; Vomiting

To determine the activity and evaluate the toxicity of uracil and tegafur in a 4:1 molar concentration (UFT; Taiho Pharmaceutical Ltd, Tokyo, Japan) plus oral calcium leucovorin in the treatment of patients with advanced colorectal carcinoma.. Forty-five patients with advanced, bidimensionally measurable metastatic colorectal carcinoma were enrolled onto the trial. None of the patients had received prior chemotherapy or biologic therapy for advanced disease. Patients received either 350 or 300 mg/m2/d UFT plus 150 mg/d leucovorin administered orally in divided daily doses every 8 hours for 28 days followed by a 7-day rest period. Response was evaluated after two courses of therapy.. Eighteen patients (three treated at 350 mg/m2/d and 15 at 300 mg/m2/d) had partial responses, and one patient had a complete response (response rate, 42.2%; 95% confidence interval, 28% to 58%). Responses were observed in sites that included liver (n = 18), lung (n = 6), and bone (n = 1). Of seven patients who received 350 mg/m2 UFT, prolonged grade 3 diarrhea developed in five; this resulted in a reduction in the UFT starting dose to 300 mg/m2/d in the remaining 38 patients. Grade 1 or 2 toxic effects included diarrhea, nausea, vomiting, abdominal cramping, anorexia, fatigue, oral mucositis, excessive lacrimation, and rash. Among 38 patients who received the 300-mg/m2/d dose, grade 3 toxic reactions included diarrhea (n = 4), vomiting (n = 2), abdominal cramping (n = 1), and fatigue (n = 2).. UFT 300 mg/m2/d plus oral leucovorin 150 mg/d administered for 28 days demonstrated significant activity against metastatic colorectal carcinoma. This oral regimen was well tolerated and devoid of the neutropenia or significant oral mucositis that complicates intravenous schedules of fluorouracil (5-FU) plus leucovorin. The results of this clinical trial will serve as the basis for a randomized phase III study to compare this oral schedule of UFT plus leucovorin with intravenous 5-FU plus leucovorin to determine the relative efficacy, impact on quality of life, and cost of the two regimens.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Diarrhea; Dose-Response Relationship, Drug; Female; Humans; Leucovorin; Male; Middle Aged; Nausea; Neoplasm Metastasis; Tegafur; Uracil

A total of 50 patients were treated weekly with 5-fluorouracil (FU), leucovorin (LV), and 4'-O-tetrahydropyranyl-doxorubicin (THP) as first-line chemotherapy for advanced breast cancer (ABC). In phase I the doses of LV (500 mg/m2, day 1) and FU (350 mg/m2, day 1) were held constant, while the dose of THP (day 1) was escalated, from the initial dose of 10 mg/m2 up to the maximum tolerated dose (MTD). Twenty-eight patients entered phase I, and MTD for THP was defined as 35 mg/m2 in this combination. Dose-limiting toxicities were myelosuppression and hepatotoxicity. In phase II, another 22 patients were treated with THP at a dose level of 30 mg/m2. Including 4 patients already treated at this dose in the first part, 25 patients were evaluable for response: 1 patient obtained a complete response (CR) and 13 showed a partial response (PR), giving an objective response rate of 56%. The median duration of response was 9.1+ months and median survival, 15.5+ months. Side effects were generally mild, with ECOG grade I and II leukopenia in 51% of all cycles and grade III in 3% of the courses. Other toxicity included nausea and vomiting (54% and 8%, respectively) and alopecia (24%), all restricted to ECOG grade I and II. Our results suggest that weekly THP/LV-FU represents an active regimen for first-line treatment of ABC with relative low toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Diarrhea; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Middle Aged; Nausea

Thirty patients with a diagnosis of metastatic adenocarcinoma of the lung were entered on a trial to evaluate the antitumor efficacy of 5-fluorouracil 370 mg/m2 daily for 5 days every four weeks in combination with folinic acid 200 mg/m2, 60 min prior to 5FU. All patients had a good performance status, bidimensionally measurable disease, and weight loss less than or equal to 5% of preillness weight. Of the 29 evaluable patients, only two (7%) had partial responses (95% confidence limits 1-24%). Eleven (38%) had stable disease and 16 (55%) progressed. The two responding patients survived 12 and 60+ weeks. The median survival of all evaluable patients was 25 weeks (range 7-60+) and that of the stable patients was 26 weeks. The principal toxicities observed were diarrhea and stomatitis. Myelosuppression was rarely dose limiting. In contrast to the results of treatment with 5FU and folinic acid in metastatic colorectal cancer and breast cancer, the results of treatment with this combination of agents have been much less encouraging in adenocarcinoma of the lung.

Topics: Adenocarcinoma; Adult; Aged; Allopurinol; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Fatigue; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Nausea; Nervous System; Stomatitis

In a recent phase II trial we have shown a favorable response rate for sequential methotrexate-5-fluorouracil (MF) in advanced gastric and colorectal cancer. We determined the therapeutic effect of sequential MF in patients with advanced gastric cancer by comparing it to 5-fluorouracil alone (F) in a randomized multicenter trial. Since February 1987 to July 1988, 133 patients with advanced gastric cancer have been prospectively randomized to receive either MF (methotrexate 100 mg/m2 i.v. push, 5-fluorouracil 600 mg/m2 i.v. drip over 15 minutes one hour after methotrexate and leucovorin 15 mg p.o. q 6 hrs x 2 beginning 24 hrs after methotrexate) of F (the same 5-fluorouracil as described for MF). Each treatment was repeated weekly x 5, then q 2 weeks. The two treatment arms were balanced for 17 clinical characteristics. The response rate was 17.9% (10 of 56 patients) in the MF arm and 1.9% (one of 53 patients) in the F arm (p less than 0.01). Median duration of response was 6.8 weeks (MF) and 6 weeks (F), respectively. Median survival time was 7.9 months (MF) and 7.3 months (F) on interim findings. Leukocytopenia and GI toxicity were significantly more common in patients receiving MF, but the degree was similar for both arms. Other side effects were minimal and no different. This schedule of MF is more effective than F in inducing remission for patients with advanced gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Drug Administration Schedule; Female; Fluorouracil; Humans; Japan; Leucovorin; Leukopenia; Male; Methotrexate; Middle Aged; Multicenter Studies as Topic; Nausea; Prospective Studies; Quality of Life; Random Allocation; Remission Induction; Stomach Neoplasms; Vomiting

Forty-five patients with metastatic colorectal carcinoma were treated with low-dose methotrexate (MTX) and 5-fluorouracil (5-FU) given sequentially. The dose of MTX was 40 mg/m2 intravenously (IV) on days 1 and 8 followed 24 hours later by 5-FU at 600 mg/m2 IV on days 2 and 9; the drugs were recycled every 28 days. Fourteen (32%) of 43 adequately treated patients had a complete or partial response lasting a median of nine months (range, 6-15 + months). Four patients had a minor response and seven patients had stable disease for a median of nine and 10 months, respectively. Toxicity included mucositis in 28 (65%) patients, diarrhea in 18 (40%), nausea in 11 (24%), and vomiting in seven (16%). Hematologic toxicity was mild: six patients had nadir white blood cell counts less than 3.5 X 10(3) cells/microL, and seven patients had a nadir platelet count less than 100 X 10(3) cells/microL. Serial biopsies and blood samples were obtained in selected patients to evaluate the effect of MTX on tissue and lymphocyte phosphoribosylpyrophosphate (PRPP) and PRPP synthetase levels.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Colonic Neoplasms; Diarrhea; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Lymphocytes; Male; Methotrexate; Middle Aged; Mucous Membrane; Nausea; Pentosephosphates; Phosphoribosyl Pyrophosphate; Phosphotransferases; Prospective Studies; Rectal Neoplasms; Ribose-Phosphate Pyrophosphokinase; Thrombocytopenia; Vomiting

Patients with visceral patterns of metastatic breast cancer were stratified according to dominant metastatic site and performance status and then randomized to therapy with cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) or CAF alternating with a "cell-cycle active" regimen including cytosine arabinoside, methotrexate with leucovorin rescue, and oncovin ( CAMELEON ). One hundred eighty-seven patients were randomized; response rate for CAF was 44% and for CAF + CAMELEON , 40%. Durations of disease control and survival were not significantly different. Toxicity of CAF was as anticipated with predominant granulocytopenia, vomiting, and alopecia. Toxicity of CAMELEON was less severe than that of CAF, and CAF toxicity was not worsened by preceding courses of CAMELEON ; however, the CAF- CAMELEON regimen was cumbersome and complex leading to both physician and patient noncompliance. Contrary to the preliminary results of a pilot study, and preliminary reports of the present trial suggesting benefit for the CAF- CAMELEON regimen the present randomized trial does not confirm any significant benefit of CAF- CAMELEON over CAF alone in patients with visceral metastatic breast cancer although this conclusion must be viewed in light of the high inevaluability rate due to patient and physician noncompliance.

Topics: Agranulocytosis; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Clinical Trials as Topic; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Administration Schedule; Drug Resistance; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Methotrexate; Nausea; Random Allocation; Thrombocytopenia; Vincristine; Vomiting

Advanced pancreatic cancer (APC) disproportionately impacts older adults. Randomized trials demonstrate improved overall survival (OS) with combination chemotherapy including 5-fluorouracil, irinotecan, leucovorin, and oxaliplatin (FOLFIRINOX) or nab-paclitaxel and gemcitabine compared with gemcitabine alone, but with increased toxicity. Older adults are at increased risk of side effects from chemotherapy. The aim of this study was to assess the efficacy and toxicity of chemotherapy in older adults with APC.. Patients diagnosed with APC from 2011 to 2016 were identified using the Manitoba Cancer Registry. Patient and treatment characteristics, toxicity, and outcomes of patients 65 years of age and above treated with palliative chemotherapy were compared by treatment regimen. OS was assessed using the Kaplan-Meier method. A Cox regression was used to identify independent predictors of OS.. A total of 87 patients aged 65 years and above received palliative chemotherapy: 52 (59.7%) FOLFIRINOX, 21 (24.1%) nab-paclitaxel and gemcitabine, and 14 (16.1%) gemcitabine, with a median age of 69 (65 to 84), 75 (65 to 88), and 73 (67 to 82), Eastern Cooperative Oncology Group (ECOG) performance status difference in hematologic toxicity between regimens (P=0.807). An increase in nonhematologic toxicity was seen with FOLFIRINOX (P<0.001), specifically neuropathy (P=0.008), fatigue (P<0.001), and nausea/vomiting (P=0.008). FOLFIRINOX was associated with improved radiologic response (P=0.05) and OS (P=0.035). PS, baseline carbohydrate antigen 19-9 level, and chemotherapy regimen were independent predictors of survival.. FOLFIRINOX is associated with improved response and OS in older adults with APC. FOLFIRINOX has a manageable safety profile in this population and should be considered in fit older adults with APC.

Topics: Aged; Albumins; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Female; Fluorouracil; Gemcitabine; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Male; Nausea; Oxaliplatin; Paclitaxel; Palliative Care; Pancreatic Neoplasms; Treatment Outcome; Vomiting

Given the biological differences between females and males, sex-specific evaluations should be carried out to obtain better cancer prevention, diagnosis, and treatment strategies. To this purpose, our aim was to evaluate sex differences for toxicity in a cohort of colorectal cancer (CRC) patients undergoing chemotherapy.. We performed a retrospective study in 329 CRC patients. Differences between males and females were tested performing the Mann-Whitney U test or the Fisher exact test. Multivariate logistic regression models were computed to evaluate the association between sex and risk of chemotherapy agent-related toxicity.. According association sex toxicity, significant differences were observed in the median number of episodes of nausea (p = 0.044), vomit (p = 0.007), heartburn (p = 0.022), thrombocytopenia (p = 0.005), mucositis (p = 0.024). Moreover, statistically significant differences between males and females were observed in the distribution of the highest toxicity grades of nausea (p = 0.024), heartburn (p = 0.016), and thrombocytopenia (p = 0.034). Females have an increased risk of vomit (p = 0.002), alopecia (p = 0.035), heartburn (p = 0.005), mucositis (p = 0.003), and lower risk for thrombocytopenia (p = 0.005).. According to the association of sex chemotherapy agent-related toxicities, females resulted on average at a significant increased risk of more common adverse events (constipation, dysgeusia, alopecia, heartburn, vomit, asthenia, nausea, pain events, and mucositis). Sex-tailored CRC chemotherapy treatment is necessary to obtain efficacy avoiding toxicity, based on patients' biological and genetic characteristics, a vision that would change CRC setting, a stable disease but still orphan of a real tailored approach.

Topics: Alopecia; Anemia; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug-Related Side Effects and Adverse Reactions; Female; Fluorouracil; Heartburn; Humans; Leucovorin; Male; Mucositis; Nausea; Retrospective Studies; Thrombocytopenia; Vomiting

Chemotherapy-related adverse events (AEs) can negatively impact the care of patients. The prevention and management of AEs often require additional medications. This study evaluated the percentages of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) undergoing second-line therapy with 5-fluorouracil (5-FU)-based regimens that experienced AEs during treatment and received medication to manage those AEs.. We conducted a retrospective observational analysis utilizing the Flatiron Health database of adult patients with mPDAC who started second-line therapy between January 2016 and August 2020. The occurrence of diarrhea, fatigue, nausea and vomiting, neuropathy, and hematologic AEs including G3/G4 anemia, neutropenia, and thrombocytopenia was assessed. The use of concomitant medications including atropine and granulocyte colony stimulating factor (G-CSF) was assessed.. Of the 825 eligible patients, 29.0% (. In patients with mPDAC who received second-line therapy, those who received liposomal irinotecan-based regimens had the lowest rates of anemia, neutropenia, and thrombocytopenia compared to FOLFIRI, FOLFIRINOX, and FOLFOX, while requiring a similar or lower level of medication to treat and manage those adverse events. Patients treated with FOLFIRI received the highest dose of pegfilgrastim to manage neutropenia. The results of this real-world analysis are consistent with prior evaluations of patients with mPDAC and highlight the importance of managing adverse events and associated cost implications.

Topics: Adenocarcinoma; Adult; Anemia; Antineoplastic Combined Chemotherapy Protocols; Atropine Derivatives; Camptothecin; Diarrhea; Fluorouracil; Granulocyte Colony-Stimulating Factor; Humans; Irinotecan; Leucovorin; Nausea; Neutropenia; Oxaliplatin; Pancreatic Neoplasms; Retrospective Studies; Thrombocytopenia; Vomiting

The outbreak of coronavirus disease 2019 (COVID-19) has affected the treatment of cancer patients, with particular regard to the management of both chemotherapy and side effects. Chemotherapy-induced nausea and vomiting (CINV) are amongst the most troublesome side effects that impair patients' adherence to treatments and their quality of life (QoL). NEPA (Akynzeo®), is an oral fixed-dose combination of netupitant [a neurokinin-1 receptor antagonist (NK1RA), 300 mg] and palonosetron [(5-hydroxytryptamine (serotonin or 5HT) type3 receptor antagonist (5HT3RA), 0.5 mg] which has been shown to be effective in preventing CINV.. This prospective study started before the outbreak of COVID-19 and was carried out during the pandemic period. The aim was to evaluate the efficacy and safety of a single oral dose NEPA plus 12 mg of dexamethasone (DEX) in patients treated with Folfoxiri plus Bevacizumab and Folfirinox. The patients were diagnosed with advanced colorectal cancer (CRC) or advanced pancreatic ductal adenocarcinoma (PDAC). They were divided into two groups: naïve patients and patients previously treated with serotonin receptor antagonists (5HT3-RA) and neurokin-1 receptor antagonists (NK1-RA).. During the overall phase, the complete response (CR) rate was 96.8% in naïve patients treated with Folfoxiri plus Bevacizumab, and 94.6% in patients treated with Folfirinox. During the acute and delayed phases, the CR rate was 92.8% and 94.2%, with Folfoxiri and Bevacizumab, as well as 96.2% and 94.6%, with Folfirinox. There was no adequate control of CINV events in patients on antiemetic prophylaxis with 5HT3-RA or NK1-RA associated with cortisone. During the overall phase, the CR rate was 74.6% with Folfoxiri plus Bevacizumab and 75.8% with Folfirinox. During the acute and delayed phases, the CR rate was 72.5% and 74.8% with Folfoxiri plus Bevacizumab, as well as 75.2% and 74.6% with Folfirinox.. This study has shown the therapeutic benefits of NEPA in the management and prophylaxis of CINV events, both in naive patients and patients previously treated with 5HT3-RA and NK1-RA. In addition, NEPA has been shown to be safe, both before and during the COVID-19 pandemic.

Topics: Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; COVID-19; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Nausea; Oxaliplatin; Palonosetron; Pandemics; Prospective Studies; Pyridines; Vomiting

Among patients with colorectal cancer (CRC) treated with oxaliplatin (L-OHP)-based chemotherapy, delayed chemotherapy-induced nausea and vomiting (CINV) have not been well controlled.. We pooled data from two prospective observational studies in Japan and one phase III clinical trial to assess whether delayed CINV could be controlled with a combination of three antiemetics adding a neurokinin-1 receptor antagonist and identified individual risk factors, using an inverse probability treatment-weighted analysis.. A total of 661 patients were evaluable in this study (median age: 64 years; 391 male, and 270 female). 3 antiemetics controlled delayed nausea (33.18% vs. 42.25%; p = 0.0510) and vomiting (4.15% vs. 16.08%; p < 0.0001) better than with 2 antiemetics. Female and 2 antiemetics were risk factors for both delayed nausea (female-odds ratio [OR]: 1.918; 95% confidence interval [CI]: 1.292-2.848; p = 0.0012; 2 antiemetics-OR: 1.485; 95% CI: 1.000-2.204; p = 0.0498) and delayed vomiting (female-OR: 2.735; 95% CI: 1.410-5.304; p = 0.0029; 2 antiemetics-OR: 4.551; 95% CI: 2.116-9.785; p = 0.0001).. Identifying individual risk factors can facilitate personalized treatments for delayed CINV. We recommend a 3-antiemetic combination prophylaxis for CRC patients treated with L-OHP-based chemotherapy, especially for female patients.

Topics: Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Clinical Trials, Phase III as Topic; Colorectal Neoplasms; Drug Therapy, Combination; Female; Fluorouracil; Humans; Japan; Leucovorin; Male; Middle Aged; Nausea; Neurokinin-1 Receptor Antagonists; Observational Studies as Topic; Organoplatinum Compounds; Oxaloacetates; Randomized Controlled Trials as Topic; Risk Factors; Sex Factors; Vomiting

Adjuvant chemotherapy is a standard treatment option for patients with stage III and high-risk stage II colon cancer. Sex is one of several factors responsible for the wide inter-patient variability in drug responses. Amalgamated data on the effect of sex on the toxicity of current standard adjuvant treatment for colorectal cancer are missing.. The objective of our study was to compare incidence and severity of major toxicities of fluoropyrimidine- (5FU or capecitabine) based adjuvant chemotherapy, with or without oxaliplatin, between male and female patients after curative surgery for colon cancer. Adult patients enrolled in 27 relevant randomized trials included in the ACCENT (Adjuvant Colon Cancer End Points) database, a large, multi-group, international data repository containing individual patient data, were included. Comparisons were conducted using logistic regression models (stratified by study and treatment arm) within each type of adjuvant chemotherapy (5FU, FOLFOX, capecitabine, CAPOX, and FOLFIRI). The following major toxicities were compared (grade III or IV and grade I-IV, according to National Cancer Institute Common Terminology Criteria [NCI-CTC] criteria, regardless of attribution): nausea, vomiting, nausea or vomiting, stomatitis, diarrhea, leukopenia, neutropenia, thrombocytopenia, anemia, and neuropathy (in patients treated with oxaliplatin).. Data from 34 640 patients were analyzed. Statistically significant and clinically relevant differences in the occurrence of grade III or IV nonhematological {especially nausea (5FU: odds ratio [OR] = 2.33, 95% confidence interval [CI] = 1.90 to 2.87, P < .001; FOLFOX: OR = 2.34, 95% CI = 1.76 to 3.11, P < .001), vomiting (5FU: OR = 2.38, 95% CI = 1.86 to 3.04, P < .001; FOLFOX: OR = 2.00, 95% CI = 1.50 to 2.66, P < .001; CAPOX: OR = 2.32, 95% CI = 1.55 to 3.46, P < .001), and diarrhea (5FU: OR = 1.35, 95% CI = 1.21 to 1.51, P < .001; FOLFOX: OR = 1.60, 95% CI = 1.35 to 1.90, P < .001; FOLFIRI: OR = 1.57, 95% CI = 1.25 to 1.97, P < .001)} as well as hematological toxicities (neutropenia [5FU: OR = 1.55, 95% CI = 1.37 to 1.76, P < .001; FOLFOX: OR = 1.96, 95% CI = 1.71 to 2.25, P < .001; FOLFIRI: OR = 2.01, 95% CI = 1.66 to 2.43, P < .001; capecitabine: OR = 4.07, 95% CI = 1.84 to 8.99, P < .001] and leukopenia [5FU: OR = 1.74, 95% CI = 1.40 to 2.17, P < .001; FOLFIRI: OR = 1.75, 95% CI = 1.28 to 2.40, P < .001]) were observed, with women being consistently at increased risk.. Our analysis confirms that women with colon cancer receiving adjuvant fluoropyrimidine-based chemotherapy are at increased risk of toxicity. Given the known sex differences in fluoropyrimidine pharmacokinetics, sex-specific dosing of fluoropyrimidines warrants further investigation.

Topics: Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Body Mass Index; Camptothecin; Capecitabine; Chemotherapy, Adjuvant; Colonic Neoplasms; Databases, Factual; Diarrhea; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Logistic Models; Male; Middle Aged; Nausea; Nervous System Diseases; Organoplatinum Compounds; Oxaliplatin; Randomized Controlled Trials as Topic; Sex Factors; Stomatitis; Thrombocytopenia; Vomiting

To compare the treatment outcomes of gemcitabine with nab-paclitaxel (GnP) and modified FOLFIRINOX (mFFX; a combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin) for metastatic pancreatic cancer.. We retrospectively analyzed consecutive patients with metastatic or recurrent pancreatic cancer treated with GnP or mFFX as the first-line chemotherapy between March 2014 and December 2019 in our hospital. Treatment outcomes were compared using propensity score matching to adjust for age, sex, performance status, carcinoembryonic antigen levels, carbohydrate antigen 19-9 levels, and disease status (metastatic or recurrent).. Five hundred sixty-eight patients were included (GnP/mFFX, 456/112). After propensity score matching, 218 patients were extracted. The median age was around 61 years, and the proportion of performance status 0 was approximately 90%. The median overall survival values were 14.6 and 15.5 months (P = 0.45), and the median progression-free survival was 7.4 months (P = 0.53) for GnP and mFFX, respectively. The disease control rates were higher in the GnP group (82.6% vs 67.9%, P = 0.02). In nonhematologic adverse events, grade 3/4 anorexia and diarrhea occurred significantly more frequently in the mFFX group.. Gemcitabine with nab-paclitaxel had a higher disease control rate and lower rates of severe anorexia and diarrhea in our propensity-matched population.

Topics: Adult; Aged; Aged, 80 and over; Albumins; Anemia; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Female; Fluorouracil; Gemcitabine; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Nausea; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxaliplatin; Paclitaxel; Pancreatic Neoplasms; Progression-Free Survival; Propensity Score; Retrospective Studies; Treatment Outcome

The use of FOLFIRINOX (a combination of oxaliplatin, irinotecan, fluorouracil, and leucovorin) is one of the therapeutic standards in pancreatic adenocarcinoma. We analyzed progression-free survival (PFS) and overall survival (OS) and their predictive factors in patients treated with FOLFIRINOX as first-line therapy in metastatic pancreatic cancer.. This multicenter retrospective analysis included patients treated with FOLFIRINOX between 2011 and 2015. The Kaplan-Meier method was used to estimate OS and PFS. The statistical comparison for survival was performed by the log-rank test. Predictive factors were estimated in multivariate analysis with the use of a Cox model.. One hundred and thirty-six patients were included (74 men, 62 women; median age, 62 years [range, 29-74 years]). The median PFS was 5.97 months (95% confidence interval, 4.4-6.63 months). The median OS was 8.93 months (95% confidence interval, 7.4-10.07 months). Prognostic factors in multivariate analysis were the use of granulocyte colony-stimulating factor, which appeared to be a good prognostic factor. Dose intensity of oxaliplatin (≥74.48%) and dose intensity of bolus of fluorouracil (>6.9%) appeared as pejorative factors.. In patients with metastatic pancreatic adenocarcinoma treated with FOLFIRINOX in first line, dose modifications at the onset of adverse effects and early use of granulocyte-colony stimulating factor seem to be associated with a better survival.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Multivariate Analysis; Nausea; Neoplasm Metastasis; Neutropenia; Outcome Assessment, Health Care; Oxaliplatin; Pancreatic Neoplasms; Prognosis; Retrospective Studies; Vomiting

Topics: Aged; Antirheumatic Agents; Arthritis; Arthritis, Psoriatic; Chemical and Drug Induced Liver Injury; Cohort Studies; Drug Substitution; Female; Folic Acid; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Nausea; Oral Ulcer; Retrospective Studies; Rheumatic Fever; Treatment Failure; Vitamin B Complex

Polypharmacy of elderly oncology patients and fragmented medication management are well-known risk factors for drug-drug interactions (DDIs). These interactions can occur among antineoplastic, ongoing chronic treatment(s) and chemotherapy-associated treatments, like antiemetics. Clinically relevant interactions based on enzyme- or transporter-inhibition phenomena of active drugs can increase the frequency of their DDIs. We describe a strongly suspected elderly cancer patient's DDI between aprepitant and opium powder in the context of an irinotecan-based regimen manifested by nightmares and visual hallucinations. We discuss this DDI's hypothetical pharmacological mechanisms and management.

Topics: Adenocarcinoma; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Arthralgia; Camptothecin; Dreams; Drug Interactions; Fluorouracil; Hallucinations; Humans; Leucovorin; Male; Nausea; Opium; Polypharmacy; Powders; Sigmoid Neoplasms

To evaluate the impact of sex on toxicity and efficacy outcomes among patients with metastatic colorectal cancer receiving first-line 5-fluorouracil-based regimens.. A pooled analysis of data sets from 5 clinical trials (NCT00115765, NCT00364013, NCT00272051, NCT00305188, NCT00384176) was performed. Kaplan-Meier analysis and log-rank testing were used to assess the differences in overall and progression-free survival between male and female subjects. Chi-square testing was used to examine the differences in the incidence of different toxicities between male and female subjects. Multivariate logistic regression analysis (adjusted for age, body mass index, Eastern Cooperative Oncology Group performance status, race, bevacizumab-containing treatment, and panitumumab-containing treatment) was further utilized to assess the impact of gender on different toxicities. Most of the patients were treated with FOLFOX (folinic acid, fluorouracil, and oxaliplatin)-based regimens.. A total of 3223 participants were included in the pooled cohort, among which were 1925 male and 1298 female subjects. Kaplan-Meier survival analysis and log-rank testing were utilized to compare overall and progression-free survival outcomes between male and female subjects. For both end points, there was no difference between male and female subjects (P = .884; P = .647, respectively). Comparing female to male subjects, female subjects were more likely to experience alopecia (20% vs. 8.6%; P < .001), all-grade diarrhea (60.3% vs. 56.7%; P = .039), all-grade nausea and vomiting (68.7% vs. 56.6%; P < .001), high-grade nausea and vomiting (7.1% vs. 4.5%; P = .002), all-grade anemia (19.6% vs. 14.2%; P < .001), all-grade neutropenia (51.1% vs. 36.6%; P < .001), and high-grade neutropenia (37.1% vs. 24.1%; P < .001). These differences were further confirmed in multivariate logistic regression analyses.. Female subjects with metastatic colorectal cancer receiving first-line chemotherapy demonstrated higher rates of a number of toxicities (essentially hematologic and gastrointestinal in nature). Additional studies into the differential effect of systemic therapy on female versus male subjects are needed.

Topics: Aged; Alopecia; Anemia; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy-Induced Febrile Neutropenia; Colorectal Neoplasms; Female; Fluorouracil; Humans; Incidence; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Nausea; Organoplatinum Compounds; Progression-Free Survival; Randomized Controlled Trials as Topic; Sex Factors; Vomiting

The aim of this study was to compare the efficacy and safety of FOLFIRINOX (5-FU/leucovorin, irinotecan, and oxaliplatin) and gemcitabine/nab-paclitaxel (GnP) in patients with advanced pancreatic cancer.. Patients with newly diagnosed advanced pancreatic cancer in Saskatchewan, Canada, from 2011 to 2016, who received FOLFIRINOX or GnP were assessed. A Cox proportional multivariate analysis was performed to evaluate prognostic variables.. One hundred nineteen eligible patients with median age of 61 years and male/female ratio of 70:49 were identified. Seventy-seven percent had metastatic disease. Of 119 patients, 86 (72%) received FOLFIRINOX and 33 (28%) were treated with GnP. Median progression-free survival of the FOLFIRINOX group was 6.0 months [95% confidence interval (CI), 4.5-7.5] versus 4.0 months (95% CI, 2.9-5.1) with GnP (P = 0.39). The median overall survival of the FOLFIRINOX group was 9.0 months (95% CI, 7-11) compared with 9.0 months (95% CI, 4.2-13.8) with GnP (P = 0.88). On multivariate analysis, albumin [hazard ratio (HR), 0.63; 95% CI, 0.41-0.97], male sex (HR, 0.65; 95% CI, 0.43-0.97), and second-line therapy (HR, 0.50; 95% CI, 0.28-0.86) were correlated with survival.. Our results showed that real-world patients with advanced pancreatic cancer treated with FOLFIIRNOX or GnP had comparable survival with different safety profile.

Topics: Aged; Albumins; Anemia; Antineoplastic Combined Chemotherapy Protocols; Cohort Studies; Community Health Planning; Deoxycytidine; Fatigue; Female; Fluorouracil; Gemcitabine; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Nausea; Outcome Assessment, Health Care; Oxaliplatin; Paclitaxel; Pancreatic Neoplasms; Proportional Hazards Models; Saskatchewan

While the majority of patients can be treated safely with fluoropyrimidine, some experience severe fluoropyrimidine-associated toxicity. The frequency and severity of these adverse events vary from patient to patient and are partially explained by genetic polymorphism into the dihydropyrimidine dehydrogenase (DPYD) gene. Carriers of the rare allelic variants DPYD*2A, DPYD*13, and DPYD D949V are more likely to experience severe adverse reactions during fluoropyrimidine-based therapy. However, these 3 genetic variants explain only a small percentage of the overall drug toxicity, and more frequent ones such as homozygous or compound heterozygous DPYD V732I can play a key role.

Topics: Aged; Alleles; Antineoplastic Combined Chemotherapy Protocols; Dihydrouracil Dehydrogenase (NADP); Female; Fluorouracil; Gastrointestinal Neoplasms; Gene Frequency; Genotype; Heterozygote; Humans; Leucovorin; Male; Nausea; Organoplatinum Compounds; Polymorphism, Genetic; Pyrimidines; Stomatitis

Single-patient methanol intoxications are a common clinical presentation, but outbreaks are rare and usually occur in settings in which there is limited access to ethanol and methanol is consumed as a substitute. In this case report, we describe an outbreak of methanol intoxications that was challenging from a public health perspective and discuss strategies for managing such an outbreak.

Topics: Acid-Base Equilibrium; Acidosis; Adult; Antidotes; Disease Outbreaks; Eating; Fomepizole; Humans; Hydraulic Fracking; Leucovorin; Male; Manitoba; Methanol; Middle Aged; Nausea; Poisoning; Pyrazoles; Renal Dialysis; Sodium Bicarbonate; Solvents; Vomiting; Young Adult

Irinotecan-based chemotherapy is a standard backbone of therapy in patients with metastatic colorectal cancer (CRC) or gastric cancer (GC). However, there is still a paucity of information concerning the efficacy and safety of irinotecan-based regimens in elderly patients.. Using the patient cohort (. Despite lower relative dose intensity in elderly patients, progression-free survival and overall survival were similar between elderly (age ≥70 years) and nonelderly (<70 years) patients in the CRC cohort (hazard ratio [HR], 1.117; 95% confidence interval [CI], 0.927-1.345;. The efficacy of the FOLFIRI regimen was similar between elderly and nonelderly patients in both the CRC and the GC cohorts. However, special attention should be paid to elderly patients because of increased risk for febrile neutropenia and asthenia.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Disease-Free Survival; Drug-Related Side Effects and Adverse Reactions; Female; Fluorouracil; Glucuronosyltransferase; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Nausea; Neoplasm Metastasis; Stomach Neoplasms; Treatment Outcome; Vomiting

Systemic chemotherapy based on 5-fluorouracil (5-FU) is a standard treatment for unresectable or recurrent colorectal cancer. Although hyperammonemia is known as one of the adverse side effects of 5-FU, a disturbance of consciousness caused by hyperammonemia is not a usual finding. We encountered a case of 5-FU-related consciousness disturbance with respiratory depression. A woman in her sixties was diagnosed with metastatic cecum cancer, involving peritoneal dissemination and hydronephrosis due to retroperitoneal invasion. After resection of the primary lesion, systemic chemotherapy, including capecitabine, irinotecan, bevacizumab and cetuximab, was administered for the metastatic lesions. As a third-line of treatment, the mFOLFOX6 plus bevacizumab regimen was administered. On the second day of the first course, the patient complained of nausea and vomiting. On third day, her consciousness level was deteriorating. The level of ammonia in the blood was abnormally high. Therefore, we diagnosed consciousness disturbance caused by hyperammonemia resulting from high-dose 5-FU infusion. The symptom improved immediately after mechanical ventilation and intravenous infusion. Renal dysfunction is considered a risk factor for hyperammonemia caused by 5-FU, and it is necessary to pay particular attention in patients with renal dysfunction who receive chemotherapy with 5-FU.

Topics: Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Colectomy; Consciousness; Female; Fluorouracil; Humans; Hyperammonemia; Leucovorin; Nausea; Organoplatinum Compounds; Peritoneal Neoplasms

The aim of this retrospective study was to show the efficacy and safety of modified FOLFOX6 plus high-dose bevacizumab (10 mg/kg/2 weeks) in the second-line or later treatment of metastatic colorectal cancer.. A total of 24 consecutive patients treated between August 2007 and August 2009 were included in this retrospective study. None of the patients had received bevacizumab as part of prior treatment.. All 24 patients received modified FOLFOX6 plus high-dose bevacizumab and were followed for a median of 36.9 months. Overall response rate was 29%. Median progression-free survival was 7.5 months, and median overall survival was 17.3 months. Grade 3/4 adverse events were: neutropenia (54.2%), leukopenia (25.0%), neuropathy (12.5%), hypertension (12.5%), thrombocytopenia (8.3%), and decreased haemoglobin, gastrointestinal haemorrhage, wound complications, nausea, diarrhoea, mucositis and fatigue (each 4.2%).. Modified FOLFOX6 plus high-dose bevacizumab may be useful in the second-line treatment of patients with metastatic colorectal cancer who have not received bevacizumab.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; Diarrhea; Disease-Free Survival; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluorouracil; Hematologic Diseases; Humans; Leucovorin; Male; Middle Aged; Mucositis; Nausea; Neoplasm Metastasis; Organoplatinum Compounds; Retrospective Studies; Severity of Illness Index; Treatment Outcome; Young Adult

This study sought to prospectively determine the frequency of delayed nausea and vomiting with oxaliplatin-based chemotherapy following day 1 prophylaxis with a 5-HT-(3) receptor antagonist and dexamethasone.. Patients with colon cancer, ≥ age 18, with a performance status ≤ 2, receiving oxaliplatin (85-100 mg/m(2)) as part of a standard folinic acid, 5-fluorouracil, oxaliplatin regimen for the first time were eligible. All patients received a 5-HT(3) receptor antagonist and dexamethasone 20 mg on day 1 prior to oxaliplatin. No routine prophylaxis for delayed emesis was given. Antiemetic outcome was recorded in patient-completed diaries for the 120-h study period following oxaliplatin administration. Primary endpoint was frequency of delayed (24-120 h) emesis (vomiting/retching).. Forty-one patients were enrolled and 39 are evaluable. Median age was 70 (34-85) and the female/male ratio was 20:19. Four patients (10%) experienced vomiting or retching during the delayed period. One patient vomited during the first 24 h after oxaliplatin. The overall (120 h) no emesis rate was 87% (34/39). Twenty-one patients (54%) developed delayed nausea. Nine patients had moderate or severe nausea. Eighteen patients (46%) took rescue antiemetics during the delayed period. Delayed and overall complete response (no emesis or use of rescue antiemetics) rates were 54% and 49%, respectively.. The use of a 5-HT(3) antagonist and dexamethasone prior to oxaliplatin results in excellent control of nausea and vomiting (CR-90%) during the 24 h after chemotherapy. However, without further antiemetic treatment, complete response in the delayed period decreased to 54%. This study supports the need for routine antiemetic prophylaxis for delayed nausea and vomiting following oxaliplatin-based chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents, Phytogenic; Colorectal Neoplasms; Dexamethasone; Female; Fluorouracil; Humans; Incidence; Leucovorin; Male; Middle Aged; Nausea; Organoplatinum Compounds; Oxaliplatin; Prospective Studies; Serotonin 5-HT3 Receptor Antagonists; Time Factors; Vomiting

To compare the efficacy and toxicity of 3 single agent chemotherapeutic regimens in low-risk gestational trophoblastic neoplasia (LRGTN).. A prospective study was conducted at a referral center in Rio de Janeiro, Brazil. Patients presenting with metastatic or non-metastatic LRGTN (risk score ≤ 6) in non-probabilistic sampling were assigned to 1 of 3 treatments: methotrexate with folinic acid rescue (MTX-CF; n=20); actinomycin D (n=20); and etoposide (n=20). Women with less than 1 year of disease-free follow-up after the first normal human chorionic gonadotropin (hCG) value were excluded. Outcome measures included primary remission rate; resistance to primary and sequential chemotherapy; period between treatment initiation and remission (hCG response); and prevalence of toxic effects.. Primary remission was achieved by 48 patients (80.0%). The remission rate with etoposide was 100.0%, while the rates with actinomycin D and MTX-CF were 90.0% and 50.0%, respectively. Efficacy of etoposide was significantly greater than the other 2 agents (P<0.001). Alopecia was the most frequent adverse effect caused by etoposide. Common to all protocols were stomatitis, nausea, and vomiting. Mean time intervals between beginning treatment and remission were similar and all 60 participants survived.. Etoposide was the most effective regimen for treating metastatic and non-metastatic LRGTN.

Topics: Adult; Alopecia; Antineoplastic Agents; Chorionic Gonadotropin; Dactinomycin; Etoposide; Female; Gestational Trophoblastic Disease; Humans; Leucovorin; Methotrexate; Nausea; Pregnancy; Prospective Studies; Remission Induction; Stomatitis; Vitamin B Complex; Vomiting; Young Adult

Controlling chemotherapy-induced nausea and vomiting(CINV)is very important for the continuation of chemotherapy. CINV can significantly affect a patient's quality of life, leading to poor compliance with further chemotherapy treatment. In this retrospective study, we assessed the efficacy of palonosetron versus granisetron for the incidence of CINV induced by mFOLFOX6 and FOLFIRI in patients with advanced colorectal cancer. Eighty-eight patients were included in the efficacy analyses: 39 patients in the palonosetron group and 49 patients in the granisetron group. The incidence of nausea in the granisetron group(Grade 1: 40. 8%, Grade 2: 10. 2% and Grade 3: 4. 1%)was significantly higher than in the palonosetron group (Grade 1: 25. 6% and Grade 2: 7. 7%, p=0. 0422). The incidence of vomiting and appetite loss in the granisetron group was not significantly higher than in the palonosetron group(p=0. 2419, p=0. 2648, respectively). This suggests that palonosetron exerts better efficacy against chemotherapy-induced nausea than granisetron in patients receiving mFOLFOX6 and FOLFIRI. Information on such analyses is useful to promote the effectiveness of cancer chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Female; Fluorouracil; Humans; Isoquinolines; Leucovorin; Male; Middle Aged; Nausea; Organoplatinum Compounds; Palonosetron; Quinuclidines; Retrospective Studies; Vomiting

Colorectal carcinomas are among the most common tumor types and are generally treated with palliative chemotherapy in case of metastatic disease. Here, we describe the case of a 58 year old woman with metastatic rectal carcinoma who developed severe gastrointestinal toxicity when the thus far well-tolerated intravenous 5-fluorouracil (5-FU)/leucovorin containing chemotherapeutic regimen was replaced by the same chemotherapeutic regimen in combination with the oral 5-FU prodrug capecitabine. This increased toxicity is probably due to the intracellular retention of polyglutamated folates induced by prior leucovorin therapy which, upon subsequent administration of capecitabine, will result in an enhanced and prolonged inhibition of the, for DNA synthesis important, enzyme thymidylate synthase, essentially creating a situation equivalent to overdosing.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Atorvastatin; Bisoprolol; Bone Neoplasms; Capecitabine; Colic; Colorectal Neoplasms; Deoxycytidine; Female; Fluorouracil; Heptanoic Acids; Humans; Hypercholesterolemia; Ileus; Leucovorin; Lymphatic Metastasis; Middle Aged; Nausea; Pyrroles; Ventricular Premature Complexes; Vomiting

Controlling of chemotherapy-induced nausea and vomiting (CINV) is very important for the continuation of chemotherapy, especially for outpatients. CINV can significantly affect a patient's quality of life, leading to poor compliance with further chemotherapy treatment. In this retrospective study, we investigated the incidence of CINV induced by mFOLFOX6 and FOLFIRI in 59 outpatients (32 males and 27 females) with advanced colorectal cancer to evaluate CINV severity using the Common Terminology Criteria for Adverse Events v.3.0. The incidence of nausea in the female group receiving FOLFIRI (grade 1: 66.7% and grade 2: 20.0%) was significantly higher than that in the male group (grade 1: 23.1% and grade 2: 7.7%, p=0.0066). The incidence of nausea in the younger (<63 years old) group receiving FOLFIRI (grade 1: 57.1% and grade 2: 28.6%) was significantly higher than that in the older (≧63 years old) group (grade 1: 35.7%, p=0.0031). Multivariable logistic regression analysis indicated that patients who were female or younger had a significantly higher incidence of nausea or vomiting than patients who were male or older, respectively, when treated with FOLFIRI. This suggests that gender (female) and age (younger) are factors predicting poor antiemetic control in outpatients receiving FOLFIRI, but not those treated with mFOLFOX6. Information on such predictive factors should be useful to promote the effectiveness of cancer chemotherapy.

Topics: Age Factors; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Female; Fluorouracil; Forecasting; Humans; Leucovorin; Logistic Models; Male; Middle Aged; Nausea; Organoplatinum Compounds; Retrospective Studies; Risk Factors; Sex Factors; Vomiting

We retrospectively analyzed comparative toxicities and efficacies of chemotherapy regimens in advanced gastric cancer (AGC) patients who achieved complete response (CR) after chemotherapy.. We reviewed the medical records of 1,203 patients, who were pathologically diagnosed as AGC in a single center between January 2001 and October 2007. On the basis of the Response Evaluation Criteria in Solid Tumors, CR was evaluated with abdominal computed tomography. Toxicities were evaluated using the National Cancer Institute's common toxicity criteria before each chemotherapy cycle.. Among the 1,203 AGC patients enrolled in this study, 568 received chemotherapy and 635 received best supportive care. The major chemotherapy regimens were 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX), docetaxel, cisplatin and 5-fluorouracil (DCF) and 5-fluorouracil, leucovorin and irinotecan (FOLFIRI). Among the 568 patients, 51 (9.0%) achieved CR (49 [8.6%] with FOLFOX [n=12], DCF [n=26], or FOLFIRI [n=11] and 2 [0.3%] with etoposide, leucovorin and 5-fluorouracil). For patients administered FOLFOX, DCF, and FOLFIRI, the median time to disease progression was 4 months (range, 1.8-59.5), 15 months (range, 2.9-31.2) and 10 months (range, 2.0-39.5), and the median survival times were 48 months (range, 5.9-74.0), 37 months (range, 14.0-86.0), and 30 months (range, 6.0-50.0), respectively. Grades 3-4 mucositis occurred mostly in patients administered DCF (n=8, 30.8%). Grades 3-4 leucopenia were observed in 1 (8.3%), 11 (42.3%), and 4 (36.4%) patients administered FOLFOX, DCF and FOLFIRI, respectively. No statistically significant differences were observed in the 3 regimens.. All 3 regimens (FOLFOX, DCF and FOLFIRI) were active and tolerable. Their efficacies and toxicities were not significantly different.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Docetaxel; Drug Therapy, Combination; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Mucositis; Nausea; Neoplasm Staging; Organoplatinum Compounds; Retrospective Studies; Stomach Neoplasms; Survival Rate; Taxoids; Tomography, X-Ray Computed; Vomiting

A 50-year-old-woman underwent high anterior resection for sigmoid colon adenocarcinoma. Modified oxaliplatin/l / -LV/ 5-FU(mFOLFOX6)was started as adjuvant treatment due to final-stage III b. Granisetron 3 mg and dexamethasone 8 mg for prophylaxis chemotherapy-induced nausea and vomiting (CINV) were administered intravenously 30 min before oxaliplatin administration. Grade 3 delayed CINV was observed at course 4. CINV could not be controlled by any rescue medications. We adopted a neurokinin-1 receptor antagonist (aprepitant) that alleviated the emetic effects of substance P. The oral aprepitant dose was 125 mg on day 1 and 80 mg on days 2 and 3. Afterward, delayed vomiting was completely controlled and chemotherapy could be continued to course 12. Aprepitant is a very active antiemetic drug for the prevention of delayed nausea and vomiting induced by mFOLFOX6 regimen.

Topics: Adenocarcinoma; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Morpholines; Nausea; Organoplatinum Compounds; Sigmoid Neoplasms; Vomiting

To date, the standard treatments for severe anticipatory nausea and vomiting is not well established. 5-HT3 antagonist is one of the effective drugs to reduce chemotherapy-induced nausea and vomiting, but had no effect on these symptoms for this patient. The patient could be successfully administered standard chemotherapy(FOLFOX or FOLFIRI, q2w)without adverse reactions by appropriate treatments in the form of increased doses of dexamethasone and normal dose administration of prochlorperazine. This report suggests a possibility that FOLFOX or FOLFIRI may be successfully treated by appropriate treatments for severe chemotherapy-induced vomiting colon cancer patients, and that this observation may lead to the improved prognosis of these patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Nausea; Neoplasm Staging; Organoplatinum Compounds; Rectal Neoplasms; Vomiting

Hiccups generally are self-limiting and of short duration. Those lasting more than 48 h or recurring at frequent intervals are termed persistent. There are numerous causes of hiccups, with medications implicated only rarely. While hiccups are usually benign, severe attacks may lead to exhaustion, eating difficulties, and affect quality of life. We report a case of severe hiccups in a patient receiving chemotherapy (oxaliplatin, 5-fluorouracil, leucovorin) for metastatic colorectal cancer. Hiccups began on the day following chemotherapy and continued constantly for over 30 h until relief was obtained by sucking the juice of a fresh lemonade. A similar pattern occurred in the next two chemotherapy cycles. Dexamethasone had been prescribed as prophylaxis against emesis and this was considered a possible cause. Withholding dexamethasone in the next cycle led to elimination of hiccups without having an impact on control of nausea and vomiting. A number of case reports have linked corticosteroids, particularly dexamethasone, to the occurrence of hiccups. Antineoplastic agents have occasionally been reported as causing hiccups; however, in most of these cases, corticosteroids, as part of the treatment protocol or as antiemetics, may have been a more likely cause. This case serves an as important reminder that adverse effects appearing during chemotherapy may not necessarily be due to antineoplastic agents. In the case of hiccups, oncology health professionals should review all medications and non drug-related factors before assigning causality.

Topics: Adenocarcinoma; Adrenal Cortex Hormones; Adult; Antidotes; Antiemetics; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cecal Neoplasms; Dexamethasone; Fluorouracil; Hiccup; Humans; Leucovorin; Male; Nausea; Organoplatinum Compounds; Oxaliplatin; Vomiting

To evaluate the efficacy and toxicity of oxaliplatin-based regimen in patients with advanced or metastatic gastric/esophagogastric junction cancer (AGC).. The clinicopathological data of a total of 180 patients with AGC were retrospectively analyzed. Responses was evaluated by RECIST criteria, and toxicity were assessed according to the NCI-CTC AE version 3.0.. 155 patients received mFOLFOX regimen, and 25 patients received regimens of mEOF and CapOX, with a total chemotherapy of 717 cycles with a median of 3 cycles. The therapeutic response was evaluated in 150 patients, showing response rate (RR) of 30.0% and disease control rate (DCR) of 74.0%. The response was evaluated in 103 of 124 patients who received the therapy as 1st line, with RR of 34.0%, DCR of 74.8%, and overall survival of 11.3 months. The major grade III/IV adverse events were leucocytopenia (14.4%), neutropenia (17.8%), thrombocytopenia (3.8%), nausea/vomiting (8.9%), and peripheral neuropathy (2.2%), with no treatment related death.. Oxaliplatin-based regimen is active and well tolerated in patients with advanced or metastatic gastric/esophagogastric junction cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Esophagogastric Junction; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Nausea; Neoplasm Staging; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Remission Induction; Retrospective Studies; Stomach Neoplasms; Survival Rate; Thrombocytopenia; Vomiting

Combination therapy of irinotecan, leucovorin (LV), and 5-fluorouracil (5-FU)(FOLFIRI regimen) has certain effect on advanced colorectal cancer. However, data of this regimen as first-line chemotherapy for Chinese patients with advanced colorectal cancer is still lacking, and its efficacy and safety still needs to be defined. This study was to explore the efficacy of FOLFIRI regimen as first-line chemotherapy on advanced colorectal cancer in Chinese patients, and observe its safety.. Clinical data of 54 chemotherapy-naive patients with advanced colorectal cancer, treated with FOLFIRI regimen from Jan. 2002 to Sep. 2005 in Cancer Center of Sun Yat-sen University, were analyzed.. Of the 54 patients, 52 were evaluable for response. The overall response rate was 42.6%, the time to progression (TTP) was 6 months, and the overall survival time was 15.2 months. The most common drug-related adverse events were neutropenia (38.9%), diarrhea (37.1%) and nausea and vomiting (50.0%). The occurrence rates of these grade 3-4 events were 5.6%, 9.3%, and 9.3%, respectively. All adverse events were tolerable.. FOLFIRI regimen is effective and well-tolerated as first-line treatment for Chinese patients with advanced colorectal cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Diarrhea; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Nausea; Neoplasm Staging; Neutropenia; Rectal Neoplasms; Remission Induction; Retrospective Studies; Survival Rate; Young Adult

Short-term infusion of 5-fluorouracil with leucovorin in combination with irinotecan or oxaliplatin has been considered as standard treatment for metastatic colorectal cancer. However, until infusion of 5-fluorouracil regimens and oxaliplatin was approved for the treatment of metastatic colorectal cancer in Japan early in 2005, combination of irinotecan with bolus 5-fluorouracil/leucovorin had been the standard treatment. This retrospective study evaluates the efficacy and safety of a modified irinotecan with bolus 5-fluorouracil/leucovorin regimen in Japanese colorectal cancer patients.. Forty-six patients untreated with chemotherapy for metastatic colorectal cancer received a modified form of the irinotecan with bolus 5-fluorouracil/leucovorin regimen, consisting of intravenous irinotecan (100 mg/m2) and l-leucovorin (10 mg/m2), and then 5-fluorouracil 500 mg/m2 as an intravenous bolus infusion, weekly for 4 weeks, repeated every 6 weeks until progression or unacceptable toxicity.. The overall response rate was 48% (95% confidence interval, 34-62%), and 48% of patients had stable disease. Median progression-free survival was 8.3 months and overall survival was 20.3 months. The incidence of grade 3 or 4 toxicity was as follows: neutropenia, 50%; diarrhea, 4%; fatigue, 13%; nausea, 7%; and vomiting, 7%. Neither treatment-related nor all-cause mortality occurred within 60 days of chemotherapy initiation. Despite the limited availability of oxaliplatin, 29 patients received an oxaliplatin-based regimen after progression.. A modified irinotecan plus bolus 5-fluorouracil/l-leucovorin regimen was an active and well-tolerated regimen in Japanese patients with advanced colorectal cancer, showing a different toxicity profile from Western patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Diarrhea; Disease-Free Survival; Drug Administration Schedule; Fatigue; Female; Fluorouracil; Humans; Injections, Intravenous; Japan; Leucovorin; Male; Middle Aged; Nausea; Neutropenia; Retrospective Studies; Survival Analysis; Treatment Outcome; Vomiting

The clinical efficacy and safety of tegafur/uracil (UFT) plus oral Leucovorin (LV) regimen for advanced or metastatic colorectal cancer were studied retrospectively. From September 2003 to March 2005, 82 patients were treated with UFT (300 mg/m(2)/day)/LV (75 mg/day) at our institute. The objective overall response rate was 14. 8% (95% confidence interval, 5.3 to 24.3%) in 54 evaluable patients. The response rate was 33.3% for previously untreated patients and 5.5% for previously treated patients, respectively. Grade 3 or more severe adverse reactions such as diarrhea or liver function abnormalities were only 7.3%. In 28 previously untreated patients,the median survival was 25.8 months with 1-and 2-year survival rates of 88.0% and 60.5%, respectively. This retrospective study demonstrated the reproducible activity and safety of UFT/LV for advanced or metastatic colorectal cancer in clinical practice.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Diarrhea; Drug Administration Schedule; Drug Combinations; Female; Humans; Leucovorin; Male; Middle Aged; Nausea; Neoplasm Recurrence, Local; Rectal Neoplasms; Remission Induction; Retrospective Studies; Survival Rate; Tegafur; Uracil; Vomiting, Anticipatory

A clinical study has been conducted to investigate whether chemotherapy with 24 hour infusion of CPT-11/oral UFT/LV is an effective and safe regimen for advanced or recurrent colorectal cancer. The chemotherapy consisted of a fixed dose of UFT (300 mg/m(2)/day)/LV (75 mg/body) orally administered daily (day 1-day 21) followed by CPT-11 (80-120 mg/m(2)) iv, as a 24-hour infusion (day 1 and day 15). This treatment was carried out weekly for 3 weeks followed by a week rest period, then repeated every 4 weeks. The MTD was reached at 120 mg/m(2) of CPT-11 (2 cases of grade 3 leucopenia and neutropenia) and 100 mg/m(2) (a case of grade 3 anorexia). Therefore the 100 mg/m(2) dose level was established as the recommended dose (RD). All patients were evaluable for efficacy; 5 PR, 4 SD and 1 PD. The overall response rate was 41.7%. The present study suggests that combination chemotherapy with CPT-11 and oral UFT/LV is well tolerated and might be a promising regimen for advanced or recurrent colorectal cancer.

Topics: Administration, Oral; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Humans; Infusions, Intravenous; Irinotecan; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Nausea; Neutropenia; Tegafur; Uracil

Toxicities and response are different when patients with advanced colorectal cancer were treated with standard FOLFOX6 regimen. Serum level of dihydropyrimidine dehydrogenase (DPD) relates to efficacy and toxicities of chemotherapy containing 5-fluorouracil (5-FU). This study was to explore relationship of DPD to serum concentration of 5-FU in colorectal cancer patients treated with FOLFOX6 regimen, and their correlation to treatment response and adverse events.. Serum level of DPD in 72 patients with colorectal cancer was detected by high-performance liquid chromatography (HPLC) before chemotherapy. Serum concentration of 5-FU at steady state was detected by HPLC after patients received FOLFOX6 regimen. Treatment response and adverse events in the patients were assessed.. Serum levels of DPD were normally distributed in 72 patients (ranged 1.55-5.94), while serum concentrations of 5-FU at steady state were not (ranged 141.1-1 741.9 microg/L). Serum level of DPD was negatively correlated with serum concentration of 5-FU (r=-0.460, P < 0.01). Occurrence of adverse events was lower when 5-FU concentration was less than 600 microg/L than when 5-FU concentration was more than 600 microg/L (P < 0.05). The mean serum concentration of 5-FU was significantly higher in patients with complete response and partial response than in patients with steady disease, and progressive disease (513.9 microg/L vs. 409.8 microg/L, and 259.3 microg/L, P < 0.05). Serum level of DPD was lower in patients suffered oral mucositis and diarrhea of grade II-IV than in patients suffered oral mucositis and diarrhea of grade 0-I (P=0.016, P=0.047). Serum level of DPD had no relation with treatment response of the patients (r=0.312, P=0.078).. DPD level and serum 5-FU concentration vary a lot among patients with colorectal cancer. DPD level negatively correlates with serum 5-FU concentration. Serum concentration of 5-FU correlates with treatment effect and toxicities.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Diarrhea; Dihydrouracil Dehydrogenase (NADP); Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Mucositis; Nausea; Organoplatinum Compounds; Rectal Neoplasms

To evaluate ambulatory patient cancer chemotherapy, the clinical response, toxicities and survival time were analysed among 19 patients with non-curative or recurrent colorectal cancer who were treated by Uracil/Tegafur (UFT) plus oral Leucovorin (UZEL) for the past 2 years. The patients were administered UFT (300 mg/m2/day) and UZEL (75 mg/body/day) for 28 days with a one-week interval every 35 days as one course.A partial response (PR) was observed in 6 patients (31.6%) and stable disease (SD) in 8. The median survival time was 16 months. Although nausea/vomiting, diarrhea and leucopenia were noted, no severe side effects were observed. These results suggested that UFT plus Leucovorin therapy might be a useful cancer chemotherapy for ambulatory patients with advanced colorectal cancer.

Topics: Administration, Oral; Adult; Aged; Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Humans; Leucovorin; Male; Middle Aged; Nausea; Neoplasm Recurrence, Local; Stomatitis; Survival Rate; Tegafur; Uracil

Concomitant treatment with 5-fluorouracil (5-FU) and Leucovorin (LV) is positioned as the standard chemotherapy against colorectal cancer. We noted the action of LV to enhance the effect of biochemical modulation by 5-FU, and made an attempt at home chemotherapy with UFT + LV by oral administration, in consideration to the convenience of patients.. The subjects of this study were 24 post-operative patients who had been assessed with Dukes D and curability C colorectal cancer with measurable metastatic lesions and who could tolerate chemotherapy.. 1 course of treatment consisted of 2 weeks of UFT at 300-400 mg/m2/day and LV at 15 mg/body/day followed by 2 weeks of drug withdrawal. The administration was conducted for 4 courses or more as the target. Unless serious adverse reaction occurred, dose increase of UFT was allowed.. The efficacy rate in the 22 patients who were assessable was 22.7%. There were 11 NC patients, accounting for half (50%) of the subjects. This home chemotherapy is expected to become an alternative chemotherapy against colorectal cancer in the future, because the treatment does not require hospitalization and has less impact on the QOL of patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Diarrhea; Drug Administration Schedule; Drug Combinations; Female; Home Care Services, Hospital-Based; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Nausea; Postoperative Care; Tegafur; Uracil; Vomiting, Anticipatory

Irinotecan (CPT11) has established activity against advanced colorectal cancer without cross-resistance with 5-fluorouracil + leucovorin-based therapy. We conducted this pilot study to evaluate the efficacy and tolerance of combination treatment with irinotecan and 5-fluorouracil (5-FU) for patients in whom combination treatment with oxaliplatin with 5-FU + leucovorin has failed.. Patients were enrolled in this study after oxaliplatin treatment had failed. The treatment protocol consisted of CPT11 (180 mg/m(2) for 90 min) on day 1 and a 2 h infusion of 200 mg/m(2) leucovorin followed by 400 mg/m(2) 5-FU as an intravenous bolus injection plus a 22 h continuous infusion of 600 mg/m(2) 5-FU. This regimen was repeated for two consecutive days every 2 weeks.. A total of 18 patients were eligible for this study and in total 144 cycles of therapy (median eight cycles) were given to these patients. Four patients (22.2%; 95% CI: 8-36.4%) achieved an objective response of partial remission (PR) and an additional seven obtained stable disease (SD) status or minor response. The median duration of response was 8 months and 14 patients were alive at the end of the study. Hematological toxicity (neutropenia) was the most common serious side effect (29.2%), followed by gastrointestinal effects (diarrhea, 28.5%). Grade II-III diarrhea was experienced for at least one cycle by each patient.. The results of treatment for patients after oxaliplatin failure are encouraging and this treatment protocol is also well tolerated by previously heavily treated patients.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Administration Schedule; Fluorouracil; Humans; Irinotecan; Leucovorin; Leukopenia; Middle Aged; Nausea; Pilot Projects; Rectal Neoplasms; Salvage Therapy; Survival Analysis; Treatment Outcome; Vomiting, Anticipatory

Our objective was to evaluate the efficacy and safety of high-dose 5-fluorouracil (5-FU) as a 24-h infusion and folinic acid (FA) (AIO regimen) plus irinotecan (CPT-11) after pre-treatment with AIO plus oxaliplatin (L-OHP) in colorectal carcinoma (CRC). Twenty-six patients with non-resectable distant CRC metastases were analyzed for second- or third-line treatment with AIO plus CPT-11 after pre-treatment with AIO plus L-OHP. On an outpatient basis, the patients received a treatment regimen comprising weekly 80 mg/m2 CPT-11 in the form of a 1-h i.v. infusion and 500 mg/m2 FA as a 1- to 2-h i.v. infusion, followed by 2000 mg/m2 5-FU i.v. administered as a 24-h infusion once weekly. A single treatment cycle comprised six weekly infusions followed by 2 weeks of rest. A total of 26 patients received 344 chemotherapy applications with AIO plus CPT-11. The main symptom of toxicity was diarrhea (NCI-CTC toxicity grade 3+4) occurring in five patients (19%; 95% CI 7-39%). Nausea and vomiting presented in two patients (8%; 95% CI 1-25%). The response rate of 26 patients can be summarized as follows: partial remission: n=7 (27%; 95% CI 12-48%); stable disease: n=9 (35%; 95% CI 17-56%) and progressive disease: n=10 (38%; 95% CI 20-59%). The median progression-free survival (n=26) was 5.8 months (range 3-13), the median survival time counted from the treatment start with the AIO plus CPT-11 regimen was 10 months (range 2-24) and counted from the start of first-line treatment (n=26) was 23 months (range 10-66). We conclude that the AIO regimen plus CPT-11 is practicable in an outpatient setting and well tolerated by the patients. Tumor control was achieved in 62% of the patients. The median survival time was 10 months and the median survival time from the start of first-line treatment (n=26) was 23 months.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Diarrhea; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Irinotecan; Leucovorin; Male; Middle Aged; Nausea; Organoplatinum Compounds; Oxaliplatin; Retrospective Studies; Vomiting

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chills; Fever; Fluorouracil; Humans; Hypotension; Infusions, Intravenous; Leucovorin; Lung Neoplasms; Male; Middle Aged; Nausea; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Vomiting

Tegafur-uracil has become an important regimen in the treatment of metastatic colorectal cancer. Tegafur is a prodrug that is converted to 5-fluorouracil (5-FU) and has been reported to be less toxic and to have a higher therapeutic index. The additional advantage of tegafur is oral administration, an important consideration to improve the quality of life in these patients. Tegafur in combination with uracil is thought to have greater anti-tumor activity due to the inhibitory effect of uracil on the degradation of 5-FU by hepatic dihydropyrimidine dehydrogenase. Tegafur with folinic acid has been reported with modest efficacy and acceptable toxicity. The purpose of this study was to evaluate the effectiveness and toxicity profile of oral tegafur-uracil plus folinic acid in Chinese patients with metastatic colorectal cancer.. Between May 1998 and August 1999, 40 patients with metastatic colorectal carcinoma were enrolled in this study. All the patients had to have measurable lesions. The initial dose of tegafur-uracil was 300 mg/m2/day for 28 days, followed by a 7-day rest period. Folinic acid was administered orally at a dose of 60 mg/day concurrently with tegafur-uracil. For patients with neutrophil count <1500/microl or a platelet count <100,000/microl after treatment, the treatment was postponed for a maximum of 2 weeks. After that time, if the neutrophil count was 1000-1500/microl and the platelet count was 70,000-100,000 microl, the dose of tegafur-uracil was reduced by 50%, and if lower values resulted, the treatment was discontinued.. Forty patients received a total of 318 courses of treatment and a response rate of 32.5% (95% CI, 18-47%), including five complete remissions and eight partial remissions, was achieved. Toxicity was mild and generally tolerable. Gastrointestinal toxicities, including diarrhea, nausea and vomiting, were the major side effects. Seven incidences (17.5%) of grade 3-4 gastrointestinal toxicity were observed. Hematological toxicities were minimal with no evidence of severe (grade 3 or 4) leukopenia and thrombocytopenia. No episode of hepatic, renal, cardiac or neurological toxicity occurred. Two patients (5%) developed transient painful fissuring erythroderma over their palms and soles (the hand-foot syndrome).. The data from our study indicate that oral tegafur-uracil plus folinic acid is an active and tolerable first-line treatment for Chinese patients with metastatic colorectal cancer, with the additional advantage of being easily administered at home.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Female; Humans; Leucovorin; Male; Middle Aged; Nausea; Rectal Neoplasms; Tegafur; Uracil; Vomiting, Anticipatory

The effects of ondansetron hydrochloride (OND) were studied through 11 courses of chemotherapy, including 70 mg/m2 of cisplatin, in 9 patients with advanced esophageal cancer. During the observation period of 5 days, 4 mg of OND was given intravenously on the day of cisplatin infusion and orally for consecutive 4 days, and nausea was controlled by over 70%. Vomiting was controlled by over 80%. The inhibitory effect of OND on nausea and vomiting was found in 72.7% on the day of cisplatin injection and 88.9% overall. No other side effects of OND except slight increases in total bilirubin and LDH were found in any patient. These findings suggest that intravenous and oral administration of OND may inhibit chemotherapy-induced nausea and vomiting in patients with advanced esophageal cancer.

Topics: Administration, Oral; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Esophageal Neoplasms; Female; Fluorouracil; Humans; Injections, Intravenous; Leucovorin; Male; Middle Aged; Nausea; Ondansetron; Vomiting, Anticipatory

The purpose of this study was to investigate the side-effects experienced by patients with colorectal cancer receiving 5-fluorouracil + folinic acid chemotherapy. A primary objective was to provide quantitative data on the incidence and severity of side-effects at each cycle of chemotherapy treatment. Twelve patients with Duke's B or Duke's C adenocarcinoma participated. Data collection was via a self-report questionnaire listing 61 possible side-effects. Participants completed a questionnaire following each cycle of chemotherapy. The response rate was 100%. Seventy-eight side-effects were reported by the sample. Fatigue was the most common side-effect (incidence = 97%) and achieved the highest C score (59/100). However, patients ranked mouth ulceration as the worst side-effect overall. Several previously unreported problems were identified, including nose bleeding, change in taste and weight loss. Although limited by a small sample size, this study suggests the problems experienced by patients undergoing 5-fluorouracil chemotherapy are many and diverse. It is concluded that investigation is needed into associations between side-effects and the role of patient characteristics in the onset of side-effects.

Topics: Adenocarcinoma; Aged; Alopecia; Antidotes; Antimetabolites, Antineoplastic; Colorectal Neoplasms; Diarrhea; Drug Therapy, Combination; Fatigue; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Nausea; Oral Ulcer; Patient Satisfaction

In spite of the high prevalence of cancer in the elderly, little information is available about the efficacy and toxicity of chemotherapy in elderly patients. In a previous study, the authors demonstrated that the combination of uracil and tegafur (UFT) with leucovorin (LV) was active and well tolerated in patients with advanced colorectal carcinoma (ACC). The objective of the current study was to determine the efficacy and toxicity of this regimen in elderly patients with ACC.. Thirty-eight unselected patients older than 70 years (median age, 74 years) with measurable ACC were included. All patients were evaluable for toxicity and response. The regimen consisted of intravenous LV 500 mg/m2 on Day 1, oral LV 15 mg every 12 hours on Days 2-14, and oral UFT 390 mg/m2 on Days 1-14. Treatment was repeated every 28 days for a minimum of 4 courses per patient.. Two hundred eighty-eight cycles of chemotherapy were delivered (median, 7 per patient). Two patients (5%) achieved a complete response and 9 (24%) a partial response, for an overall response rate of 29%. Toxicity was mild, without dose-limiting myelosuppression. Four patients (10%) experienced Grade 3-4 diarrhea, 1 patient had Grade 3-4 nausea/vomiting, and 1 had Grade 3-4 mucositis. Grade 3-4 toxicity was more frequent among women than men (38% vs. 4%, P < 0.05).. Treatment with oral UFT modulated with LV is effective, well tolerated, and feasible on an outpatient basis for elderly patients with ACC. However, elderly women should be followed closely for the early detection of toxicity.

Topics: Administration, Oral; Aged; Aged, 80 and over; Ambulatory Care; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Carcinoma; Clinical Protocols; Colonic Neoplasms; Diarrhea; Feasibility Studies; Female; Humans; Injections, Intravenous; Leucovorin; Male; Nausea; Rectal Neoplasms; Remission Induction; Sex Factors; Tegafur; Uracil; Vomiting

Multiple studies have shown that leucovorin-fluorouracil regimens are modestly superior to fluorouracil alone in the treatment of advanced colorectal cancer. Laboratory data suggest that iododeoxyuridine could further enhance the efficacy of leucovorin-fluorouracil regimens. This report describes the Phase I clinical evaluation of a leucovorin-fluorouracil-iododeoxyuridine chemotherapy regimen. Twenty-four patients received treatment with leucovorin (500 mg/m2), fluorouracil (500 mg/m2), and iododeoxyuridine (escalating doses) on days 1 and 8 of a 21-day cycle. The maximum tolerated dose of iododeoxyuridine was 1200 mg/m2, with a recommended Phase II dose of 1000 mg/m2. Myelosuppression (leukopenia) was dose limiting; other commonly observed treatment toxicities were nausea/vomiting, mucositis, and hyperlacrimation. Although the 1200 mg/m2 dose was tolerated during the initial few cycles of therapy, chronic administration could not be maintained secondary to dose-limiting neutropenia. Since neutropenia was dose limiting, in a follow-up study, 10 patients received a modified regimen (treatment on days 1 and 6 instead of days 1 and 8) with the addition of granulocyte colony-stimulating factor (days 8-19). The addition of granulocyte colony-stimulating factor, however, did not permit further escalation of the iododeoxyuridine dose. Three partial responses and six minor responses were observed. Phase II studies of this regimen are ongoing in advanced colorectal and advanced pancreatic cancer to determine response rates in these diseases.

Topics: Adult; Aged; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase I as Topic; Colorectal Neoplasms; Dose-Response Relationship, Drug; Evaluation Studies as Topic; Fatigue; Female; Fluorouracil; Granulocyte Colony-Stimulating Factor; Humans; Idoxuridine; Leucovorin; Male; Middle Aged; Nausea; Neutropenia; Vomiting

From March 1992 to May 1994, 105 patients with esophageal carcinoma patients were treated with CF/5-Fu-DDP (group A, n = 40) or 5-Fu-DDP (group B, n = 65) protocol. The response rate (CR+PR) was 80% in group A and 60% in group B. (P < 0.01) Induction chemotherapy was followed by surgery or radiation therapy. The incidence of nausea, vomiting, cardiotoxicity and leukopenina was higher in group A than in group B. Buccal mucositis, diarrhea, abdomenal pain and skin pigmentation were noted only in group A. However, the toxic effects were tolerable. The results suggest that the CF/5-Fu-DDP regimen is more effective than 5-Fu-DDP regimen and may be one of the best chemotherapy regimens for the treatment of esophageal carcinoma.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Esophageal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Nausea; Vomiting

Encouraging results have recently been reported for studies using folinic acid in combination with 5-fluorouracil (5-FU) in the treatment of patients with gastrointestinal (GI) malignancies. Thirty-six patients with advanced colorectal cancer with unequivocal evidence of progression while treated with fluoropyrimidines were treated with a six-day continuous infusion of 500 mg/m2/d of folinic acid initiated 24 hours before a five-day course of 5-FU administered as an intravenous (IV) bolus of 370 mg/m2/d. An initial dose of 250 mg/m2/d of 5-FU was used in patients previously treated with ionizing radiation and/or a nitrosourea. Three objective partial responses were observed. The overall median duration of survival was 8.1 months. Toxicity was acceptable and not in excess of that expected for 5-FU alone.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Evaluation; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Nausea; Rectal Neoplasms; Stomatitis; Thrombocytopenia

From January to November, 1981, 28 patients with unresectable squamous cell carcinoma of the esophagus were treated with two cycles of chemotherapy combining vincristine (V), methotrexate (M), folinic acid rescue, and cisplatin (P) on days 1 and 21. Split-course radiation therapy was delivered thereafter from day 42 on. Hematologic, renal, and neurologic tolerance was acceptable, but most of the patients experienced nausea and vomiting. Results evolution at day 40 showed a 61% partial response (PR) rate and a 7% complete response (CR) rate. One month after the end of radiation therapy, 43% PR and 32% CR were obtained. Median response duration was 8 months. Median survival was 11.6 months for patients overall, yielding 12.9 months for responders and 5.9 months for nonresponders. Based on the response rate obtained with combined chemotherapy, a randomized trial of VMP initial chemotherapy is currently being undertaken by our cooperative group to study whether such an initial treatment could improve resectability and radiation-mediated local control along with survival rate.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Esophageal Neoplasms; Evaluation Studies as Topic; Female; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Nausea; Time Factors; Vincristine; Vomiting

Fifteen patients with advanced or recurrent gynecologic malignancy were treated with high-dose methotrexate (HDMTX) (1-8 g/M2) and citrovorum factor rescue (10-100 mg/M2). One complete response (13%) and two improved responses occurred in eight patients (25%) with squamous cell carcinoma and one of seven patients (14%) with nonsquamous nontrophoblastic carcinoma had stable disease for 7 months. The median duration of survival in the squamous group was 9 months and in the nonsquamous groups 6.5 months. Mean serum MTX concentrations were proportional to the doses administered and typical two compartment plasma disappearance curves were seen. Adverse toxic reactions were not observed at serum MTX levels less than 7.8 X 10(-7) M at 24 hr and 1 X 10(-7) M at 48 hr post-MTX. Hematopoietic toxicity occurred most frequently with leukopenia observed in 19.5% of courses. Hepatic, renal, gastrointestinal, and dermatologic toxicities were observed infrequently. Drug-induced nephrotoxicity occurred in one patient and possibly related leukoencephalopathy occurred in another patient. On the basis of the relatively low response rate observed in this trial and the high expense of HDMTX therapy, the value of such therapy may be limited in advanced nontrophoblastic gynecologic cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemical and Drug Induced Liver Injury; Drug Evaluation; Female; Genital Neoplasms, Female; Hematologic Diseases; Humans; Kidney Diseases; Kinetics; Leucovorin; Methotrexate; Middle Aged; Nausea; Time Factors

Twenty-nine patients with metastatic breast cancer were treated with fluorouracil, adriamycin, cyclophosphamide (FAC), and methotrexate (MTX), with or without leukovorin rescue. Of 24 evaluable patients, one achieved a complete remission and 17 had partial responses. The overall objective response rate was 75%. The median survival from initiation of chemotherapy for the responding patients was 18 months. Four patients (17%) with stable disease had a median survival of 25 months. The addition of MTX to FAC chemotherapy did not improve the therapeutic efficacy of this combination; it did, however, increase the overall toxicity, especially the infectious complications when compared to FAC alone.

Topics: Alopecia; Antineoplastic Combined Chemotherapy Protocols; Bacterial Infections; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Humans; Leucovorin; Methotrexate; Nausea; Neutropenia; Stomatitis; Vomiting

We have shown previously that methotrexate pretreatment of murine leukemia and human colon carcinoma cell cultures results in augmented intracellular accumulation of 5-fluorouracil metabolites. Both of these drugs are commonly used for the treatment of women with breast cancer; thus, sequencing of methotrexate before 5-fluorouracil was evaluated in vitro using a human mammary carcinoma cell line, 47-DN. Intracellular 5-fluorouracil accumulation was maximally increased 4-fold in cultures pretreated with 10 microM methotrexate for 24 hr. This enhancement of 5-fluorouracil metabolism was associated with increased intracellular levels of 5-phosphoribosyl 1-pyrophosphate, resulting from the antipurine effect of methotrexate. Brief exposure to exogenous hypoxanthine at physiological concentrations reversed the biochemical synergism between methotrexate and 5-fluorouracil. Other antimetabolites associated with elevations of 5-phosphoribosyl 1-pyrophosphate enhanced intracellular accumulation of 5-fluorouracil up to 2.5-fold. In cloning assays, 18 hr of methotrexate pretreatment followed by 5-fluorouracil resulted in optimal synergistic cytotoxicity, which could be prevented if high concentrations of leucovorin were given between methotrexate and 5-fluorouracil administration. Since these results indicated that optimal breast tumor toxicity in vitro was achieved by 18- to 24-hr sequencing of methotrexate and 5-fluorouracil, clinical toxicity study was carried out to assess whether this drug schedule could be tolerated. Seven patients with advanced cancer were treated with 21 courses of sequential therapy. No toxicity occurred with 38% of treatment courses; mild to moderate leukopenia and mucositis occurred with 29 and 38% of courses respectively. Toxicity was related to treatment interval and not cumulative drug dose or elevated serum methotrexate levels. These clinical results suggest that Phase II studies evaluating 24-hr-sequenced methotrexate and 5-fluorouracil in breast cancer are warranted.

Topics: Breast Neoplasms; Cell Line; Drug Administration Schedule; Drug Evaluation; Drug Interactions; Drug Synergism; Female; Fluorouracil; Humans; Hypoxanthines; Leucovorin; Leukopenia; Methotrexate; Nausea; Phosphoribosyl Pyrophosphate; Time Factors

Response rates of metastatic soft part sarcomas to chemotherapy have varied from 27 and 44% for our ALOMAD and OMAD protocols to 46-55% reported for CYVADIC. The present combination, CYOMAD, consists of the induction part of ALOMAD (vincristine, high-dose methotrexate with citrovorum factor rescue, Adriamycin and DTIC) alternating with a condensed version of CYVADIC (cyclophosphamide, vincristine, adriamycin and DTIC). Forty-one patients with advanced soft-part sarcomas were entered on the CYOMAD program of whom 36 were considered evaluable. Complete responses (CR) were seen in four patients had partial (PR) in five patients for a major response rate of 25%. Responders had an overall longer survival than nonresponders (20 versus 13 months). Toxicity was substantial with both gastrointestinal side effects and myelosupression common. Possible Adriamycin cardiotoxicity was noted in four patients. Cyomad offered no therapeutic advantage over previous protocols and was even less well tolerated than some.

Topics: Adolescent; Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dacarbazine; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Drug Therapy, Combination; Female; Heart Diseases; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Nausea; Sarcoma; Vincristine; Vomiting

Topics: Administration, Oral; Adolescent; Amphotericin B; Anorexia; Blood Platelets; Blood Transfusion; Candidiasis; Drug Eruptions; Humans; Infusions, Parenteral; Injections, Intramuscular; Leucovorin; Methotrexate; Nausea; Osteosarcoma; Pneumothorax; Stomatitis; Vomiting

Topics: Adolescent; Age Factors; Alkaline Phosphatase; Aspartate Aminotransferases; Bone Neoplasms; Child; Doxorubicin; Drug Therapy, Combination; Evaluation Studies as Topic; Female; Hematopoietic System; Humans; Leucovorin; Male; Methotrexate; Mucous Membrane; Nausea; Neoplasm Metastasis; Osteosarcoma

Topics: Anemia, Hypochromic; Chemical and Drug Induced Liver Injury; Chromosome Aberrations; Chromosome Disorders; Drug Eruptions; Folic Acid Antagonists; Headache; Humans; Leucovorin; Methotrexate; Mouth Diseases; Mouth Mucosa; Nausea; Psoriasis; Vertigo