levoleucovorin and Fatigue

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

Many clinical trials for older patients with metastatic colorectal cancer have been conducted, and fluoropyrimidine and bevacizumab are standard treatments. However, the relationship between age and the efficacy and safety of this treatment is unclear in older metastatic colorectal cancer patients.. Individual data from two phase II studies on older (≥75 years), non-frail patients with metastatic colorectal cancer treated with uracil-tegafur/leucovorin or S-1 combined with bevacizumab were collected. Patient characteristics were evaluated with multiple regression analyses for survival outcomes, using the Cox proportional hazard model and linear regression analyses for the worst grade of adverse events.. We enrolled 102 patients with a median age of 80 years (range, 75-88 years). Of the 70 patients who died, seven (10%) died of causes unrelated to disease or treatment. The study treatment was discontinued due to adverse events in 19 patients (18.6%), with 63% aged ≥85 years. The adverse event that most commonly resulted in treatment discontinuation was grade 2 fatigue (21%). Chronological age was not associated with progression-free survival (Hazard ratio, 1.03; P = 0.40) or overall survival (Hazard ratio, 1.02; P = 0.65). Age was weakly associated with non-hematologic adverse events (regression coefficient [R], 0.27; P = 0.007), especially fatigue (R, 0.23; P = 0.02) and nausea (R, 0.19; P = 0.06), but not with hematologic (R, 0.05; P = 0.43) or bevacizumab-related (R, -0.06; P = 0.56) adverse events.. The efficacy of fluoropyrimidine plus bevacizumab was age-independent in patients with metastatic colorectal cancer aged ≥75 years, and attention should be paid to non-hematologic adverse events as age increases.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colonic Neoplasms; Colorectal Neoplasms; Disease-Free Survival; Fatigue; Fluorouracil; Humans; Leucovorin; Rectal Neoplasms

SEQUOIA compared efficacy and safety of adding pegilodecakin (PEG), a pegylated recombinant human interleukin (IL)-10, with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) in patients following progression on first-line gemcitabine-containing therapy with metastatic pancreatic ductal adenocarcinoma (PDAC).. SEQUOIA, a randomized, global phase III study, compared FOLFOX with PEG + FOLFOX as second line in gemcitabine-refractory PDAC. Patients were randomly assigned 1:1 (PEG + FOLFOX:FOLFOX) and stratified by prior gemcitabine and region. Eligible patients had only one prior gemcitabine-containing treatment. Primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), response evaluation per Response Evaluation Criteria in Solid Tumor (RECIST) 1.1, and safety. Exploratory analyses included biomarkers related to immune activation.. Between March 1, 2017, and September 9, 2019, 567 patients were randomly assigned PEG + FOLFOX (n = 283) or FOLFOX (n = 284). Most (94.7%) patients received prior gemcitabine plus nab paclitaxel. OS was similar comparing PEG + FOLFOX versus FOLFOX (median: 5.8. PEG added to FOLFOX did not improve efficacy in advanced gemcitabine-refractory PDAC. Safety findings were consistent as previously observed from PEG with chemotherapy; toxicity was manageable and tolerable. Exploratory pharmacodynamic results were consistent with immunostimulatory signals of the IL-10R pathway.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Deoxycytidine; Disease Progression; Drug Resistance, Neoplasm; Fatigue; Female; Fluorouracil; Gemcitabine; Humans; Interleukin-10; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Outcome Assessment, Health Care; Oxaliplatin; Pancreatic Neoplasms; Polyethylene Glycols; Thrombocytopenia

The optimal therapeutic strategy in patients with rectal cancer and synchronous unresectable metastases remains unknown. We evaluated the efficacy of FOLFIRINOX induction therapy in this setting.. Chemotherapy-naïve patients received at least 8 cycles of FOLFIRINOX. The primary end-point was the 4-month disease control (4 m DC) rate. Tumour responses were centrally reviewed and assessed by computed tomography scan for metastases (Response Evaluation Criteria in Solid Tumours criteria) and magnetic resonance imaging for rectal tumorus. With a Simon 2-stage design and a targeted (H1) 4 m DC > 75%, 65 patients were enrolled from July 2012 to February 2015: male, 78%; median age, 61 years; performance status, 0-1, 98%; liver metastases, 92%; ≥2 metastatic sites, 63%.. Fifty-six (85%) of the 65 patients received the 8 planned FOLFIRINOX cycles. The primary objective was achieved (4 m DC rate: 94%; 95% confidence interval [CI], 86.3-97.8). Primary tumour symptoms decreased from 72% at baseline to 10% at 4 months. Response rate was 86%, and a >70% primary tumour volume decrease was seen in 63% of patients. Forty-four patients (68%) had at least one grade 3 side-effect; no toxic deaths occurred. Median follow-up was 35.0 months (95% CI, 31.3-43.7). Median progression-free survival and overall survival were 10.9 m (95% CI, 8.8-12.9) and 33.4 m (95% CI, 22.6-38.2), respectively.. Upfront FOLFIRINOX is feasible and allows good local and distant control. It therefore offers the opportunity to choose the best therapeutic strategy for each patient and to personalise treatment according to the local and distant efficacy results of this induction step.. Clinicaltrials.gov, NCT01674309.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Fatigue; Female; Fluorouracil; Follow-Up Studies; Gastrointestinal Diseases; Hematologic Diseases; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Liver Neoplasms; Lung Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Oxaliplatin; Paresthesia; Progression-Free Survival; Rectal Neoplasms; Remission Induction; Tomography, X-Ray Computed; Treatment Outcome

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

Nanoliposomal irinotecan showed activity in a phase 2 study in patients with metastatic pancreatic ductal adenocarcinoma previously treated with gemcitabine-based therapies. We assessed the effect of nanoliposomal irinotecan alone or combined with fluorouracil and folinic acid in a phase 3 trial in this population.. We did a global, phase 3, randomised, open-label trial at 76 sites in 14 countries. Eligible patients with metastatic pancreatic ductal adenocarcinoma previously treated with gemcitabine-based therapy were randomly assigned (1:1) using an interactive web response system at a central location to receive either nanoliposomal irinotecan monotherapy (120 mg/m(2) every 3 weeks, equivalent to 100 mg/m(2) of irinotecan base) or fluorouracil and folinic acid. A third arm consisting of nanoliposomal irinotecan (80 mg/m(2), equivalent to 70 mg/m(2) of irinotecan base) with fluorouracil and folinic acid every 2 weeks was added later (1:1:1), in a protocol amendment. Randomisation was stratified by baseline albumin, Karnofsky performance status, and ethnic origin. Treatment was continued until disease progression or intolerable toxic effects. The primary endpoint was overall survival, assessed in the intention-to-treat population. The primary analysis was planned after 305 events. Safety was assessed in all patients who had received study drug. This trial is registered at ClinicalTrials.gov, number NCT01494506.. Between Jan 11, 2012, and Sept 11, 2013, 417 patients were randomly assigned either nanoliposomal irinotecan plus fluorouracil and folinic acid (n=117), nanoliposomal irinotecan monotherapy (n=151), or fluorouracil and folinic acid (n=149). After 313 events, median overall survival in patients assigned nanoliposomal irinotecan plus fluorouracil and folinic acid was 6.1 months (95% CI 4.8-8.9) vs 4.2 months (3.3-5.3) with fluorouracil and folinic acid (hazard ratio 0.67, 95% CI 0.49-0.92; p=0.012). Median overall survival did not differ between patients assigned nanoliposomal irinotecan monotherapy and those allocated fluorouracil and folinic acid (4.9 months [4.2-5.6] vs 4.2 months [3.6-4.9]; 0.99, 0.77-1.28; p=0.94). The grade 3 or 4 adverse events that occurred most frequently in the 117 patients assigned nanoliposomal irinotecan plus fluorouracil and folinic acid were neutropenia (32 [27%]), diarrhoea (15 [13%]), vomiting (13 [11%]), and fatigue (16 [14%]).. Nanoliposomal irinotecan in combination with fluorouracil and folinic acid extends survival with a manageable safety profile in patients with metastatic pancreatic ductal adenocarcinoma who previously received gemcitabine-based therapy. This agent represents a new treatment option for this population.. Merrimack Pharmaceuticals.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Pancreatic Ductal; Deoxycytidine; Diarrhea; Fatigue; Female; Fluorouracil; Gemcitabine; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Liposomes; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Pancreatic Neoplasms; Treatment Outcome; Vomiting

The antiangiogenic agent aflibercept (ziv-aflibercept in the United States) in combination with 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) significantly improved survival in a phase III study of patients with metastatic colorectal cancer (mCRC) previously treated with an oxaliplatin-based regimen. In the present analysis, outcomes were evaluated in prespecified subgroups to assess the consistency of the treatment effect.. Patients were randomised to receive FOLFIRI plus aflibercept or placebo every 2weeks until disease progression or unacceptable toxicity occurred. Efficacy and safety outcomes were analysed with respect to demographic and baseline characteristics, and stratification factors (prior bevacizumab treatment and Eastern Cooperative Oncology Group performance status).. Median overall survival (OS, months [95.34% confidence interval (CI)]) for aflibercept versus placebo was 12.5 (10.8-15.5) versus 11.7 (9.8-13.8) in patients with prior bevacizumab treatment and 13.9 (12.7-15.6) versus 12.4 (11.2-13.5) in patients with no prior bevacizumab treatment. The p value for interaction was 0.5668, indicating there was no heterogeneity in these subgroups. For OS and progression-free survival (PFS), there was a significantly greater benefit (at the 2-sided 10% level) of treatment for patients with liver only metastases versus patients with no liver metastases/liver metastases with other organ involvement (p value for interaction: 0.0899 [OS]; 0.0076 [PFS]). There was no evidence of heterogeneity in treatment effect in any of the other subgroups examined.. The benefits of aflibercept in combination with FOLFIRI in patients with mCRC previously treated with oxaliplatin were maintained across the specified patient subgroups, including in patients with or without prior bevacizumab treatment.

Topics: Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Diarrhea; Double-Blind Method; Drug Administration Schedule; Fatigue; Fluorouracil; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Middle Aged; Neoplasm Metastasis; Neutropenia; Prospective Studies; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Treatment Outcome

The combination of bevacizumab and bolus 5-fluorouracil, leucovorin and irinotecan is highly effective in patients with metastatic colorectal cancer (mCRC). This randomised, multicenter, non-comparative phase II trial assessed the efficacy and safety of bevacizumab plus oral capecitabine plus irinotecan (XELIRI) or infusional 5-fluorouracil, leucovorin plus irinotecan (FOLFIRI) as first-line therapy for patients with mCRC.. Patients received bevacizumab 7.5mg/kg on day 1 plus XELIRI (irinotecan 200mg/m(2) on day 1 and oral capecitabine 1,000 mg/m(2) bid on days 1-14) every 3 weeks or bevacizumab 5mg/kg on day 1 plus FOLFIRI (5-fluorouracil 400mg/m(2) on day 1 plus 2,400 mg/m(2) as a 46-h infusion, leucovorin 400mg/m(2) on day 1, and irinotecan 180 mg/m(2) on day 1) every 2 weeks. Patients aged ≥ 65 years received a lower dose of capecitabine (800 mg/m(2) twice daily). The primary endpoint was 6-month progression-free survival (PFS) rate.. A total of 145 patients were enrolled (bevacizumab-XELIRI, n=72; bevacizumab-FOLFIRI, n=73). The 6-month PFS rate was 82% (95% confidence intervals (CI) 71-90%) in the bevacizumab-XELIRI arm and 85% (95% CI 75-92%) in the bevacizumab-FOLFIRI arm. In both the bevacizumab-XELIRI and bevacizumab-FOLFIRI arms, median PFS and overall survival (OS) were 9 and 23 months, respectively. The most frequent toxicities were grade 3/4 neutropenia (bevacizumab-XELIRI 18%; bevacizumab-FOLFIRI 26%) and grade 3 diarrhoea (12% and 5%, respectively).. This randomised non-comparative study demonstrates that bevacizumab-XELIRI and bevacizumab-FOLFIRI are effective regimens for the first-line treatment of patients with mCRC with manageable toxicity profiles.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Diarrhea; Disease-Free Survival; Drug Administration Schedule; Fatigue; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Neoplasm Metastasis; Neutropenia; Quality of Life; Time Factors; Treatment Outcome; Venous Thrombosis

This double-blind, phase III study aimed to demonstrate that sunitinib plus FOLFIRI (fluorouracil, leucovorin, and irinotecan) was superior to placebo plus FOLFIRI in previously untreated metastatic colorectal cancer (mCRC).. Patients were randomly assigned to receive FOLFIRI and either sunitinib (37.5 mg per day) or placebo (4 weeks on treatment, followed by 2 weeks off [schedule 4/2]) until disease progression. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, safety, and patient-reported outcomes. The correlation between genotype and clinical outcomes was also analyzed.. In all, 768 patients were randomly assigned to sunitinib plus FOLFIRI (n = 386) or placebo plus FOLFIRI (n = 382). Following a second prespecified interim analysis, the study was stopped because of potential futility of sunitinib plus FOLFIRI. Final results are reported. The PFS hazard ratio was 1.095 (95% CI, 0.892 to 1.344; one-sided stratified log-rank P = .807), indicating a lack of superiority for sunitinib plus FOLFIRI. Median PFS for the sunitinib arm was 7.8 months (95% CI, 7.1 to 8.4 months) versus 8.4 months (95% CI, 7.6 to 9.2 months) for the placebo arm. Sunitinib plus FOLFIRI was associated with more grade ≥ 3 adverse events and laboratory abnormalities than placebo (especially diarrhea, stomatitis/oral syndromes, fatigue, hand-foot syndrome, neutropenia, thrombocytopenia, anemia, and febrile neutropenia). More deaths as a result of toxicity (12 v four) and significantly more dose delays, dose reductions, and treatment discontinuations occurred in the sunitinib arm.. Sunitinib 37.5 mg per day (schedule 4/2) plus FOLFIRI is not superior to FOLFIRI alone and has a poorer safety profile. This combination regimen is not recommended for previously untreated mCRC.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Diarrhea; Double-Blind Method; Drug Administration Schedule; Fatigue; Female; Fluorouracil; Humans; Indoles; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Pyrroles; Sunitinib; Thrombocytopenia; Treatment Outcome

This phase I study assessed the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics, and preliminary antitumor effects of sunitinib combined with modified FOLFOX6 (mFOLFOX6).. Patients with advanced solid malignancies received mFOLFOX6 in 2-week cycles with escalating sunitinib doses (25, 37.5, and 50 mg/day) on three schedules: 2 weeks on, 2 weeks off (2/2); 4 weeks on, 2 weeks off (4/2); or continuous daily dosing (CDD). Patients received up to 8 treatment cycles (Schedule 2/2 and CDD schedule) or 6 cycles (Schedule 4/2). An expansion cohort enrolled patients with metastatic colorectal cancer at the Schedule 2/2 MTD.. Overall, 53 patients were enrolled, with 43 evaluable for dose-limiting toxicity (DLT). On Schedule 2/2 (n = 18), DLTs occurred in three patients at 50 mg/day (grade 4 neutropenia [n = 1]; grades 3 and 4 thrombocytopenia [n = 2]) and two patients achieved partial responses (PRs). On Schedule 4/2 (n = 13), 37.5 mg/day exceeded the MTD with two DLTs (febrile neutropenia and grade 4 hypokalemia, respectively). On the CDD schedule (n = 12), the MTD was 25 mg/day; one DLT (grade 3 stomatitis) was reported and two patients achieved PRs. The most common adverse events were neutropenia, fatigue, and thrombocytopenia. No clinically significant drug-drug interactions were apparent between sunitinib, its metabolite SU12662, and mFOLFOX6.. Sunitinib combined with mFOLFOX6 had acceptable tolerability. The MTDs were sunitinib 50 mg/day on Schedule 2/2 and 25 mg/day on the CDD schedule. A MTD for Schedule 4/2 was not established.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Dose-Response Relationship, Drug; Drug Administration Schedule; Fatigue; Female; Fluorouracil; Humans; Indoles; Leucovorin; Male; Metabolic Clearance Rate; Middle Aged; Neoplasms; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Pyrroles; Sunitinib; Thrombocytopenia; Treatment Outcome

Combination chemotherapy with FOLFIRINOX (oxaliplatin, irinotecan, fluorouracil, and leucovorin) was shown to be effective in a large phase III trial.. The purpose of this study was to examine the tolerance and effectiveness of FOLFIRINOX as practiced outside of the confines of a clinical trial and to document any dose modifications used by practicing oncologists.. Data on patients with all stages of pancreatic adenocarcinoma treated with FOLFIRINOX at three institutions was analyzed for efficacy, tolerance, and use of any dose modifications.. Total of 61 patients was included in this review. Median age was 58 years (range: 37 to 72 years), 33 were male (54.1%) and majority had ECOG performance of 0 or 1 (86.9%, 53 patients). Thirty-eight (62.3%) had metastatic disease, while 23 (37.7%) were treated for locally advanced or borderline resectable disease. Patients were treated with a median number of four cycles of FOLFIRINOX, with dose modifications in 58.3% (176/302) of all cycles. Ten patients had stable disease (16.4%), four had a partial response (6.6%) while eight had progressive disease (13.1%) on best imaging following therapy. Median progression-free survival and overall survival were 7.5 months and 13.5 months, respectively. The most common grade 3-4 adverse event was neutropenia at 19.7% (12 cases), with 4.9% (3 cases) rate of febrile neutropenia. Twenty-one patients (34.4%) were hospitalized as a result of therapy but there were no therapy-related deaths. Twenty-three (37.7%) had therapy eventually discontinued as a result of adverse events.. Despite substantial rates of adverse events and use of dose modifications, FOLFIRINOX was found to be clinically effective in both metastatic and non-metastatic patients. Regimen toxicity did not detract from overall response and survival.

Topics: Abdominal Pain; Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Dose-Response Relationship, Drug; Drug Administration Schedule; Fatigue; Female; Fluorouracil; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Pancreatic Neoplasms; Treatment Outcome

Liposomal drugs have a better tolerance profile and are highly accumulated in the tumor environment, properties that promise an optimal radiosensitization. We investigated the feasibility of the combination of 5-fluorouracil/lecovorin-based radio-chemotherapy with the administration of high weekly dose of a liposomal platinum formulation (Lipoplatin).. Lipoplatin was given at a dose of 120 mg/m(2)/week, 5-fluorouracil at 400mg/m(2)/week (Day 1), whereas radiotherapy was given through 3.5-Gy fractions on Days 2, 3, and 4. Two groups of 6 patients received four and five consecutive cycles, respectively.. Minimal nephrotoxicity (18.2% Grade 1) and neutropenia (9% Grade 3) was noted. Fatigue Grade 2 appeared in 25% of cases. Abdominal discomfort was reported by 18% of patients. No liver, kidney, gastric, or intestinal severe acute or late sequellae were documented, although the median follow-up of 9 months is certainly too low to allow safe conclusions. A net improvement in the performance status (from a median of 1 to 0) was recorded 2 months after the end of therapy. The response rates assessed with computed tomography, endoscopy, and biopsies confirmed 33% (2 of 6) tumor disappearance in patients treated with four cycles, which reached 80% (4 of 5) in patients receiving five cycles.. Lipoplatin radio-chemotherapy is feasible, with minor hematological and nonhematological toxicity. The high complete response rates obtained support the testing of Lipoplatin in the adjuvant postoperative or preoperative radio-chemotherapy setting for the treatment of gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Fatigue; Feasibility Studies; Female; Fluorouracil; Humans; Kidney; Leucovorin; Male; Middle Aged; Neutropenia; Radiation Tolerance; Radiotherapy Dosage; Stomach Neoplasms

Oxaliplatin, 5-fluorouracil (5-FU), and leucovorin (LV) are standard first-line treatments for patients with metastatic colorectal cancer (mCRC). The aim of this multicentre, open-label, phase IIIb study was to assess the addition of oxaliplatin to two different 5-FU regimens.. Patients with previously untreated mCRC were randomised to arm A [two-weekly oxaliplatin 85 mg/m(2) + either continuous intravenous infusion (CIV) of 5-FU without LV or two-weekly bolus and CIV 5-FU + LV (LV5FU2)] or arm B (5-FU CIV or LV5FU2 alone). Irinotecan monotherapy was planned on progression.. A total of 725 patients were enrolled. After a fixed follow-up of 2 years for each patient, 2-year survival rates were 27.3% and 24.8% in arms A and B, respectively (hazard ratio 0.93; 95% confidence interval 0.78-1.10). The addition of oxaliplatin significantly improved response rates (54.1 versus 29.8%; P < 0.0001) and median progression-free survival (7.9 versus 5.9 months; P < 0.0001). The most common grade 3-4 toxic effects were neutropenia (arm A, 33%; arm B, 5%), diarrhoea (arm A, 14%; arm B, 8%), and fatigue (arm A, 9%; arm B, 8%).. Despite improved rates of tumour control, these results failed to demonstrate a survival benefit from the addition of oxaliplatin to infused 5-FU and lend further support to the use of sequential monotherapy in some patients with mCRC.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Diarrhea; Disease Progression; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Fatigue; Fluorouracil; Follow-Up Studies; Humans; Infusions, Intravenous; Irinotecan; Leucovorin; Neoplasm Metastasis; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Survival Analysis; Time Factors; Treatment Outcome

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

The National Surgical Adjuvant Breast and Bowel Project C-08 trial was designed to investigate the safety and effectiveness of adding bevacizumab to modified infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) 6 regimen for the adjuvant treatment of patients with stage II or III colon cancer. We present safety information in advance of the planned analysis of efficacy.. Among 2,710 randomly assigned patients, demographic factors were balanced. Patients received modified FOLFOX6 every 2 weeks x 12 or modified FOLFOX6 plus bevacizumab (5 mg/kg every 2 weeks x 26, experimental group).. Overall rates of grade 4 or 5 toxicities were nearly identical in the FOLFOX6 and FOLFOX6 plus bevacizumab arms (15.2% and 15.0%, respectively). Six-month mortality rates were 0.96% and 0.90% for the control and experimental groups, respectively. Grade 3+ toxicities that occurred more often in the experimental arm versus control arm included hypertension (12% v 1.8%, respectively), wound complications (abdominal incisional hernia or infusion port dehiscence/inflammation; 1.7% v 0.3%, respectively), pain (11.1% v 6.3%, respectively), and proteinuria (2.7% v 0.8%, respectively). Grade 2+ neuropathy was increased in the experimental arm versus the control arm (grade 2, 33% v 29%, respectively; grade 3, 16% v 14%, respectively; and grade 4, < 1% each). In the experimental arm versus control arm, significantly less thrombocytopenia (1.4% v 3.4%, respectively) and fewer allergic reactions (3.1% v 4.7%, respectively) were observed. Advanced age was associated with a significantly greater rate of grade 4 and 5 toxicities regardless of treatment.. Bevacizumab with modified FOLFOX6 is well tolerated in the surgical adjuvant setting in these patients. No significant increase in GI perforation, hemorrhage, arterial or venous thrombotic events, or death with the addition of bevacizumab to modified FOLFOX6 has been observed. Follow-up for potential delayed adverse effects and efficacy is ongoing.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Chemotherapy, Adjuvant; Colonic Neoplasms; Diarrhea; Disease-Free Survival; Fatigue; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Nervous System Diseases; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Pain; Treatment Outcome

Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor. It potentiates cytotoxic drug activity in human xenografts. This phase I/II dose-finding study evaluated gefitinib in combination with a 5-fluorouracil (5-FU)/folinic acid (FA)/irinotecan (FOLFIRI-AIO) regimen in patients with metastatic colorectal cancer.. Patients received gefitinib 250 mg per day, and escalating doses of FOLFIRI-AIO i.v. (dose level (DL) 1: 1600/ 500/60 mg/m(2); DL2: 1600/500/80 mg/m(2); DL3: 2000/500/ 80 mg/m(2)) weekly x 6. Dose-limiting toxicity (DLT) was determined in patients who completed 1 cycle of therapy.. 13 patients were enrolled. 1 out of 6 patients on DL1 exhibited DLT (acute psychosis), and a total of 7 patients received DL2. Of those, 3 patients had DLT during cycle 1 (nausea/vomiting n = 2; diarrhea n = 1, fatigue n = 2). Recruitment was stopped at this DL because of the unfavorable toxicity profile observed during the first and subsequent treatment cycles (out of 7 patients: nausea/vomiting grade 3 n = 2, diarrhea grade 3 n = 2; fatigue n = 3). Only 1 patient showed a partial remission, and 2 patients experienced stabilization of disease.. Dose escalation had to be stopped early because of gastrointestinal toxicity and fatigue. This treatment regimen did not seem advantageous with respect to efficacy in comparison with FOLFIRIAIO alone.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Fatigue; Female; Fluorouracil; Gastrointestinal Diseases; Gefitinib; Humans; Irinotecan; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Quinazolines; Risk Assessment; Treatment Outcome

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

Patients with hepatic or renal dysfunction are often treated with 5-fluorouracil (5-FU), but there are few data to confirm the safety of this practice.. Patients with solid tumors were eligible if they were able to fit into one of three organ dysfunction cohorts: I, creatinine >1.5 but < or =3.0 mg/dl and normal bilirubin; II, bilirubin >1.5 but <5.0 mg/dl with normal creatinine; or III, bilirubin > or =5.0 mg/dl with normal creatinine. 5-FU doses were escalated separately within each of the three cohorts. Leucovorin (LV) dosage was fixed at 500 mg/m(2). 5-FU was given as a 24-h infusion at 1000, 1800 or 2600 mg/m(2), and plasma concentrations were measured every 3 h during the first two infusions for each patient.. Sixty-four patients were treated. Toxicities did not appear to be related to organ dysfunction cohort. A weekly dose of of 5-FU 2600 mg/m(2) produced dose-limiting toxicity (DLT) in six of 20 evaluable patients. These DLTs included grade 3 fatigue (n = 3), grade 2 neutropenia precluding weekly dosing (n = 1), grade 3 thrombocytopenia (n = 1) and grade 3 mental status changes (n = 1). There was no relationship between serum bilirubin or serum creatinine and 5-FU clearance.. Patients with elevated bilirubin may be safely started on a weekly regimen of 5-FU 2600 mg/m(2) with leucovorin 500 mg/m(2) as a 24-h continuous infusion.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Bilirubin; Creatinine; Dose-Response Relationship, Drug; Fatigue; Female; Fluorouracil; Humans; Infusions, Intravenous; Kidney Diseases; Leucovorin; Liver Diseases; Male; Middle Aged; Neoplasms; Neutropenia; Thrombocytopenia

Irinotecan (CPT-11) and 5-fluorouracil (5-FU)/leucovorin are active agents in colorectal cancer. A sequence-dependent synergism of SN-38 followed by 5-FU/leucovorin in vitro led us to conduct a phase I trial of CPT-11 followed by 5-FU/leucovorin to determine the maximum tolerated dose (MTD) and toxicities of this regimen and to obtain preliminary indications of its activity in patients with advanced solid tumors.. Fifty-six patients were enrolled in sequential cohorts to receive escalating doses of CPT-11 (90 min infusion) on day 1, followed by leucovorin 20 mg/m(2) (intravenous push) and 5-FU (90 min infusion) on days 2-5 of each 21-day cycle.. A total of 347 treatment cycles (median 4, range 1-25) were administered. Dose-limiting toxicities were diarrhea, neutropenia and fatigue. Nine patients with colorectal cancer and one with gastric cancer had partial or minor responses. Eight of the 10 had prior chemotherapy.. CPT-11 and 5-FU/leucovorin, as constituents of this novel mechanism-based schedule, have promising activity in patients who have received prior chemotherapy. The recommended phase II/III starting doses are CPT-11 275 mg/m(2) over 90 min on day 1, and 5-FU 400 mg/m(2) plus leucovorin 20 mg/m(2) on days 2-5 every 21 days. This combination can be administered safely to this schedule if there is strict adherence to the 90 min infusion time for both CPT-11 and 5-FU.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Diarrhea; Dose-Response Relationship, Drug; Drug Administration Schedule; Fatigue; Female; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intravenous; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasms; Neutropenia

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

In advanced gastric cancer, we investigated feasibility and activity of sequential chemotherapy with docetaxel after an intensive weekly regimen consisting of cisplatin, epidoxorubicin, fluorouracil, leucovorin (PELF) plus filgrastim. Chemotherapy-naive patients with relapsed or metastatic gastric cancer received 8 weekly administrations of chemotherapy with cisplatin 40 mg/m(2), fluorouracil 500 mg/m(2), epidoxorubicin 35 mg/m(2), 6S-stereoisomer of leucovorin 250 mg/m(2) and glutathione 1.5 g/m(2). On the other days filgrastim 5 microg kg(-1) was administered by subcutaneous injection. Subsequently, patients with partial response or stable disease received 3 cycles of docetaxel 100 mg/m(2) every 3 weeks. 40 patients have been enrolled and they are evaluable for response and toxicity. After the PELF regimen, 3 patients achieved complete response, 13 patients showed partial response, 21 patients had stable disease and 3 patients progressed (40% response rate; 95% CI 25% to 55%). After docetaxel, 9 out 34 patients improved the outcome (26.5%); 7 patients with stable disease achieved partial response and 2 patients with partial response achieved complete response. The overall response rate in the 40 patients was 57.5% (95% CI, 42.5% to 72.5%). The PELF regimen did not cause any grade IV toxicity, the most frequent grade III acute side-effects were thrombocytopenia and vomiting which occurred in the 10% of 320 PELF cycles. Docetaxel caused grade III-IV neutropenia and thrombocytopenia in the 10% and the 19% of cycles respectively. Fatigue was a frequent side-effect during both PELF and docetaxel chemotherapy. The sequential application of docetaxel after PELF chemotherapy gained major objective responses with manageable toxicity. This strategy is worth of further investigation in the setting of palliative or neoadjuvant chemotherapy.

Topics: Adult; Aged; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Administration Schedule; Drug Therapy, Combination; Epirubicin; Fatigue; Female; Fluorouracil; Glutathione; Granulocyte Colony-Stimulating Factor; Humans; Infusions, Intravenous; Injections, Subcutaneous; Leucovorin; Male; Middle Aged; Neutropenia; Paclitaxel; Stomach Neoplasms; Taxoids; Thrombocytopenia; Treatment Outcome

The objective of this Phase II study was to define the response rate, safety profile, and toxicity of oral uracil and ftorafur (UFT) with leucovorin (UFT/LV) as a palliative treatment for patients with squamous cell carcinoma of the head and neck (SCCHN).. Patients with metastatic or recurrent SCCHN with an Eastern Cooperative Oncology Group performance status < 2 and adequate organ function were enrolled in an institutional review board-approved trial. Prior induction or adjuvant chemotherapy was permitted provided 6 months had elapsed since the last chemotherapy. Patients were treated with UFT 300 mg/m(2) per day and leucovorin 90 mg per day administered in three doses daily for 28 days followed by a 7-day break for a 35-day cycle. Planned intrapatient dose modifications were based on individual toxicity. Patients were removed from the study for progression of disease or unacceptable toxicity.. One hundred six cycles of UFT/LV had been administered to 42 patients as of January 1, 2000. The most common toxicities, in descending order of incidence, were anemia, pain, fatigue, diarrhea, nausea, mucositis, and anorexia. Clinically significant toxicities attributable to UFT/ LV were primarily gastrointestinal. On an intent-to-treat basis, three patients (7%) achieved a complete response, and six patients (14%) achieved a partial response. The overall response rate was 21% (95% confidence interval, 10--37%).. UFT/LV therapy is feasible in this patient population and is generally well tolerated. Response rates are similar to the rates expected with continuous-infusion 5-fluorouracil. UFT/LV should be studied further both alone and in combination therapy for patients with SCCHN.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anemia; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Disease-Free Survival; Fatigue; Female; Head and Neck Neoplasms; Humans; Leucovorin; Male; Middle Aged; Pain; Palliative Care; Tegafur; Treatment Outcome; Uracil

This study was designed to determine response rate, survival and toxicity associated with combination chemotherapy delivered intra-arterially to liver in patients with hepatic metastases of colorectal origin refractory to standard systemic treatment. A total of 28 patients who failed prior systemic treatment with fluoropyrimidines received a median of 5 cycles of intra-arterial treatment consisting of 5-fluorouracil 700 mg/m(2)/d, leucovorin 120 mg/m(2)/d, and cisplatin 20 mg/m(2)/d for 5 consecutive days. Cycles were repeated at intervals of 5-6 weeks. A major response was achieved in 48% of patients: complete response in 8% and partial response in 40%. The median duration of response was 11.5 months. Median survival was 12 months at a median follow up of 12 months. On multivariate analysis, the only variables with a significant impact on survival were response to treatment and performance status. Toxicity was moderate: grades III-IV neutropenia occurred in 29% of patients. Most of the patients complained of fatigue lasting for a few days following each cycle. There were no cases of hepatobiliary toxicity. These findings indicate that regional intra-arterial treatment should be considered in selected patients with predominantly liver disease following failure of standard treatment.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Colorectal Neoplasms; Drug Resistance, Neoplasm; Fatigue; Female; Fluorouracil; Humans; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Male; Middle Aged; Neutropenia; Survival Analysis; Treatment Outcome

Biochemical modulation of 5-Fluorouracil activity with Leucovorin has been well documented in colorectal cancer. Several studies have shown increased efficacy of 5-fluorouracil in combination with alpha interferon. We therefore initiated a phase II trial of dual modulation of 5-fluorouracil with leucovorin and alpha interferon to evaluate outcomes in patients with metastatic carcinoma of the colon.. Patients with metastatic colon carcinoma with expected survival > 4 months and performance status of ECOG < or = 2 were treated weekly with Leucovorin 400 mg i.v. followed by 5-FU 600 mg/m2 i.v. bolus. Alpha interferon 3-9 million units was administered subcutaneously every Monday, Wednesday and Friday. Patients were analyzed for toxicity, tumor response and survival.. Sixteen patients with a median age of 66 years were treated. Three patients were not evaluable for response but were evaluable for toxicity. Grades 3 and 4 toxicities were neutropenia, diarrhea, mucositis, nausea and vomiting, fatigue, fever, asthenia and elevated hepatic enzymes. One patient died from complications associated with diverticulitis and neutropenia. Objective response rate was 23% (95% confidence interval 4-46%) and median survival was 11.5 months (95% confidence interval 6.3-19 months). Thirty-eight percent of the patients were alive at one year and 19% at two years.. The combination of 5-fluorouracil, leucovorin and alpha interferon as administered in this phase II study did not result in enhanced response rate or survival. However this regimen was associated with considerable toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemical and Drug Induced Liver Injury; Colonic Neoplasms; Combined Modality Therapy; Diverticulitis; Drug Administration Schedule; Fatigue; Female; Fluorouracil; Gastrointestinal Diseases; Humans; Immunologic Factors; Interferon-alpha; Leucovorin; Life Tables; Male; Middle Aged; Neutropenia; Survival Analysis; Treatment Failure

The rest/activity circadian cycle has been used as a reference for chemotherapy administration at specific times to improve tolerability and efficacy. Because cancer processes may be associated with alterations of circadian rhythms, the rest/activity cycle was monitored noninvasively to assess its relationship with tumor response, survival, and quality of life in 200 patients with metastatic colorectal cancer. Patients wore an actigraph, a wristwatch that records the number of accelerations per minute, for 3 days before receiving chronomodulated chemotherapy. The circadian rhythms in activity were estimated by two robust parameters: the autocorrelation coefficient at 24 h (r24), and the dichotomy index (I

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Circadian Rhythm; Colorectal Neoplasms; Drug Administration Schedule; Fatigue; Female; Fluorouracil; Humans; Hydrocortisone; Leucovorin; Male; Middle Aged; Multivariate Analysis; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Prognosis; Prospective Studies; Quality of Life; Severity of Illness Index; Sleep Wake Disorders; Survival Analysis; Treatment Outcome

The palliation of symptoms and improvement of quality of life are important aspects of therapy in patients with incurable metastatic cancer. This article describes the preliminary results of a phase I study of uracil and tegafur, an orally available fluorouracil (5-FU) derivative combined with oral leucovorin plus weekly intravenous paclitaxel. While the daily oral dose of UFT is fixed at 300 mg/m2 plus 90 mg leucovorin on days 1 to 28, paclitaxel is escalated in 10 mg/m2 steps starting with 50 mg/m2 weekly as a 1-hour infusion. To date, 26 patients with a median age of 57 years have been entered into the protocol and have received a median 2.2 cycles of therapy. Dose level 4 (paclitaxel 80 mg/m2) has been recently completed. Major dose-limiting toxicities were fatigue syndrome (two patients) and diarrhea (five patients). Preliminary responses have been observed in three of 14 currently evaluable patients. This protocol is taking the development of protracted 5-FU administration--given orally as UFT--in combination with paclitaxel one step further, using paclitaxel in a dose-dense, weekly schedule. It is hoped that an active regimen for the outpatient treatment of solid tumors will be developed.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Fatigue; Female; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neoplasms; Paclitaxel; Tegafur; Uracil

From October 1995 to June 1997, 19 chemotherapy-naive patients with pathology-proven locally advanced or metastatic biliary tract carcinomas (BTC) were enrolled. The regimen consisted of 5-fluorouracil (5-FU) 2600 mg/m2 and leucovorin (LV) 150 mg by weekly 24 h infusion for 6 weeks and followed by a 2 week break. The treatment was terminated if disease progressed, the patient refused or unacceptable toxicity occurred. All patients required a Port-A catheter insertion and were treated at outpatient clinics by portable infusion pumps. There were 12 males and seven females with a median age of 62 years (range 45-77). The primary tumor sites were nine intrahepatic cholangiocarcinomas (CC), three perihilar CC, one distal BTC and six gallbladder cancers. A total of 179 chemotherapy sessions were given with a mean of 9.5 (range 2-18). Eighteen patients were evaluable for response. The response rates were: 33% (six of 18) partial response (PR), 39% (seven of 18) stable disease (SD) and 28% (five of 18) progressive disease (PD). All of the patients were evaluable for toxicity. The most common toxicities were mild fatigue (nine of 19, 47%), loss of appetite (nine of 19, 47%), skin hyperpigmentation (five of 19, 26%) and diarrhea (two of 19, 11%). Only one patient had grade IV myelotoxicity with sepsis but without treatment-related death. The median time to progression was 4 months. The overall median survival time was 7.0 months. The median survival time of the PR was not reached, SD was 8.0 months and PD 3.5 months. In conclusion, weekly high-dose 5-FU with LV by 24 h infusion in an outpatient setting for patients with BTC is effective, only mildly toxic and deserves further study.

Topics: Aged; Anorexia; Antidotes; Antimetabolites, Antineoplastic; Biliary Tract Neoplasms; Bone Marrow; Diarrhea; Dose-Response Relationship, Drug; Drug Combinations; Fatigue; Female; Fluorouracil; Humans; Hyperpigmentation; Infusion Pumps; Leucovorin; Male; Middle Aged; Skin; Treatment Outcome; Vomiting

5-Fluorouracil plus folinic acid and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) are effective salvage therapies for metastatic breast cancer patients. Paclitaxel and 5-fluorouracil have additive cytotoxicity in MCF-7 cell lines. We performed a phase II trial of paclitaxel 175 mg/m2 over 3 hours on day I followed by folinic acid 300 mg over 1 hour before 5-fluorouracil 350 mg/m2 on days 1 to 3 every 28 days (TFL) in women with metastatic breast cancer. Analysis is reported on 37 patients with a minimum of 6 months follow-up who received a total of 192 cycles of TFL: nine cycles (5%) were associated with grade 3/4 neutropenia requiring hospitalization; seven (4%) cycles in two patients required granulocyte colony-stimulating factor due to neutropenia; no patient required platelet transfusions. Grade 3/4 nonhematologic toxicities were uncommon. Among the 34 patients evaluable for response, there were three complete responses (9%) and 18 partial responses (53%) for an overall response rate of 62%. Of the 19 evaluable patients with prior doxorubicin exposure, 11 (58%) responded compared with nine of 15 (60%) without prior doxorubicin. Plasma paclitaxel concentrations were measured at the completion of paclitaxel infusion and at 24 hours in 19 patients. TFL is an active, well-tolerated regimen in metastatic breast cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Fatigue; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Mucous Membrane; Neoplasm Metastasis; Nervous System Diseases; Paclitaxel

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

To explore the relationship between fatigue and self-efficacy, and quality of life (QoL) during chemotherapy of patients with breast, lung or gastrointestinal cancers. This study is a descriptive-correlational research. The study population comprised of patients with breast, lung and gastrointestinal cancer treated at the outpatient chemotherapy unit. Patients' self-efficacy and QoL were assessed using Functional Assessment of Chronic Illness Therapy-Fatigue scale and Strategies Used by Patients to Promote Health scale. The sample included 236 patients receiving chemotherapy for lung cancer (30.9%), gastrointestinal (25.8%) or breast cancers (25.4%). The patients had little confidence in performing self-care self-efficacy during chemotherapy for the management of illness and chemotherapy-related side effects. The study found that the patients with cancer were moderately fatigued and all the domains of QoL of patients with cancer undergoing chemotherapy were considerably impaired. Positive correlations were found between self-efficacy scores and fatigue scores (p < 0.001), and QoL scores (p < 0.001). Better self-efficacy beliefs were associated with better QoL and lower fatigue. Improving the cancer patients' self-confidence in performing self-care behaviours may have a positive impact on performing cognitive and behavioural fatigue management strategies and can influence positively the patients' QoL during chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Colorectal Neoplasms; Fatigue; Female; Fluorouracil; Gastrointestinal Neoplasms; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Paclitaxel; Quality of Life; Self Care; Self Efficacy; Surveys and Questionnaires; Turkey

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

Stereotactic body radiation therapy (SBRT) is an emerging treatment option for unresectable pancreatic cancer, and is postulated to be more effective and less toxic than conventionally fractionated intensity modulated radiation therapy (IMRT).. We retrospectively reviewed unresectable stage I-III pancreatic adenocarcinoma treated from 2008 to 2016 at our institution with SBRT (five fractions, 30-33 Gy) or IMRT (25-28 fractions, 45-56 Gy with concurrent chemotherapy). Groups were compared with respect to overall survival (OS), local and distant failure, and toxicity. Log-rank test and Cox proportional hazards regression model, and competing risks methods were used for univariate and multivariate analysis.. SBRT patients (n = 44) were older than IMRT (n = 226) patients; otherwise there was no significant difference in baseline characteristics. There was no significant difference in OS or local or distant failure. There was no significant difference in rates of subsequent resection (IMRT =17%, SBRT =7%, p = .11). IMRT was associated with more acute grade 2+ gastrointestinal toxicity, grade 2+ fatigue, and grade 3+ hematologic toxicity (p = .008, p < .0001, p = .001, respectively).. In this analysis, SBRT achieves similar disease control outcomes as IMRT, with less acute toxicity. This suggests SBRT is an attractive technique for pancreatic radiotherapy because of improved convenience and tolerability with equivalent efficacy. However, the lack of observed advantages in disease control with this moderate-dose SBRT regimen may suggest a role for increasing SBRT dose, if this can be accomplished without significant increase in toxicity.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Capecitabine; Chemoradiotherapy; Deoxycytidine; Diarrhea; Fatigue; Female; Fluorouracil; Gemcitabine; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Mucositis; Multivariate Analysis; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Pancreatic Neoplasms; Proportional Hazards Models; Radiation Injuries; Radiosurgery; Radiotherapy, Intensity-Modulated; Retrospective Studies; Survival Rate; Thrombocytopenia

The robustness of the circadian timing system (CTS) was correlated to quality of life and predicted for improved survival in cancer patients. However, chemotherapy disrupted the CTS according to dose and circadian timing in mice. A continuous and repeated measures longitudinal design was implemented here to characterize CTS dynamics in patients receiving a fixed circadian-based chemotherapy protocol. The rest-activity rhythm of 49 patients with advanced cancer was monitored using a wrist actigraph for 13 days split into four consecutive spans of 3-4 days each, i.e., before, during, right after and late after a fixed chronotherapy course. The relative amount of activity in bed vs. out of bed (I

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Circadian Rhythm; Fatigue; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Monitoring, Physiologic; Motor Activity; Neoplasm Metastasis; Neoplasm Staging; Neoplasms; Organoplatinum Compounds; Oxaliplatin; Prognosis; Prospective Studies; Rest; Weight Loss

Chemotherapy-induced neutropenia has been associated with prolonged survival selectively in patients on a conventional schedule (combined 5-fluorouracil, leucovorin, and oxaliplatin [FOLFOX2]) but not on a chronomodulated schedule of the same drugs administered at specific circadian times (chronoFLO4). The authors hypothesized that the early occurrence of chemotherapy-induced symptoms correlated with circadian disruption would selectively hinder the efficacy of chronotherapy.. Fatigue and weight loss (FWL) were considered to be associated with circadian disruption based on previous data. Patients with metastatic colorectal cancer (n = 543) from an international phase 3 trial comparing FOLFOX2 with chronoFLO4 were categorized into 4 subgroups according to the occurrence of FWL or other clinically relevant toxicities during the initial 2 courses of chemotherapy. Multivariate Cox models were used to assess the role of toxicity on the time to progression (TTP) and overall survival (OS).. The proportions of patients in the 4 subgroups were comparable in both treatment arms (P = .77). No toxicity was associated with TTP or OS on FOLFOX2. The median OS on FOLFOX2 ranged from 16.4 (95% confidence limits [CL], 7.2-25.6 months) to 19.8 months (95% CL, 17.7-22.0 months) according to toxicity subgroup (P = .45). Conversely, FWL, but no other toxicity, independently predicted for significantly shorter TTP (P < .0001) and OS (P = .001) on chronoFLO4. The median OS on chronoFLO4 was 13.8 months (95% CL, 10.4-17.2 months) or 21.1 months (95% CL, 19.0-23.1 months) according to presence or absence of chemotherapy-induced FWL, respectively.. Early onset chemotherapy-induced FWL was an independent predictor of poor TTP and OS only on chronotherapy. Dynamic monitoring to detect early chemotherapy-induced circadian disruption could allow the optimization of rapid chronotherapy and concomitant improvements in safety and efficacy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Disease Progression; Drug Administration Schedule; Drug Chronotherapy; Fatigue; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Multivariate Analysis; Organoplatinum Compounds; Predictive Value of Tests; Proportional Hazards Models; Treatment Outcome; Weight Loss

FOLFIRINOX (5-fluorouracil [5-FU], oxaliplatin, and irinotecan) as compared with gemcitabine in pancreatic cancer (PC) has superior activity and increased toxicity. The bolus 5-FU contributes to the toxicity. We hypothesized that the elimination of bolus 5-FU and use of hematopoietic growth factor will improve the safety profile without compromising the activity of FOLFIRINOX.. Sixty patients with PC treated with modified FOLFIRINOX (no bolus 5-FU) were reviewed. Patients were divided into metastatic or nonmetastatic (locally advanced or borderline resectable) disease. Toxicity, response rate, progression-free survival, and overall survival were evaluated.. Nonmetastatic and metastatic disease were present in 24 (40%) and 36 (60%) patients, respectively. The incidence of grade 4 neutropenia, grade 3/4 diarrhea, and fatigue were 3%, 13%, and 13%, respectively. Response rate was 30%. The median progression-free survival for nonmetastatic disease was 13.7 months (95% confidence interval [CI], 9.6-24.6 months), and that for metastatic disease was 8.5 months (95% CI, 3.7-11.0 months), respectively. The median overall survival for nonmetastatic disease was 17.8 months (95% CI, 9.9 months to not estimable), and that for metastatic disease was and 9.0 months (95% CI, 7.1 months to not estimable), respectively.. Modified FOLFIRINOX has an improved safety profile with maintained efficacy in metastatic PC. Modified FOLFIRINOX has promising activity in nonmetastatic disease.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; CA-19-9 Antigen; Camptothecin; Diarrhea; Disease-Free Survival; Dose-Response Relationship, Drug; Fatigue; Female; Filgrastim; Fluorouracil; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Pancreatic Neoplasms; Polyethylene Glycols; Recombinant Proteins; Retrospective Studies; Treatment Outcome

There are a few clinical trials of combination chemotherapy of oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX-4) in Japan, and its efficacy and safety have not been confirmed yet, especially clinical experience in patients with prior chemotherapy.. To analyze the efficacy and safety of FOLFOX-4 in patients with colorectal cancer who received prior chemotherapy.. Twenty patients were treated with FOLFOX-4 beginning in April 2005. Three patients were entered into the safety study, and seventeen patients were treated on a reduced dose, because they had already received heavy doses of prior chemotherapy.. Number of prior chemotherapy was 1 regimen in 7 patients, more than two regimens in 13 patients. The median course of FOLFOX-4 was 10 (4-12), which gave an overall response rate of 20.0% and a median time to progression of 5.0 months. The median survival time was 15.6 months from initiation of the FOLFOX-4, and 28.5 months from the first-line treatment. Grade 3/4 neutropenia was seen in 12 patients (60%), and neuropathy was observed in 11 patients (55%). No response was seen in irinotecan based regimens after FOLFOX-4.. FOLFOX-4 in patients with pretreated colorectal cancer was effective, and contributed to prolonged life with the TTP of 5 months. However, hematological toxicity was high despite the reduced dose. Further extension of prolonged life is anticipated by administering incorporating molecular targeting agents.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Administration Schedule; Fatigue; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neutropenia; Organoplatinum Compounds; Rectal Neoplasms; Salvage Therapy; Survival Rate

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 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

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