levoleucovorin and Thrombocytopenia

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colectomy; Colorectal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Thrombocytopenia

To conduct a systematic literature review and meta-analysis to estimate the incidence of anaemia, leucopoenia, neutropenia and thrombocytopenia associated with MTX plus folic acid among patients with rheumatic diseases.. We searched MEDLINE, PubMed and EMBASE through August 2016 for all randomized controlled clinical trials with a MTX monotherapy arm. We excluded randomized controlled clinical trials for cancer and included only double-blind studies that reported on haematologic adverse events. Studies were excluded if patients did not receive folic acid or leucovorin supplementation. Full text articles were assessed by two independent reviewers. Incidence estimates were calculated using random-effects models.. Of 1601 studies identified, 30 (1.87%) were included, representing 3858 patients; all had RA. Seventeen trials reported on anaemia (n = 2032), 17 reported on leucopoenia (n = 2220), 16 reported on neutropenia (n = 2202) and 12 reported on thrombocytopenia (n = 1507). The incidence for any anaemia was 2.55% (95% CI 0.60-5.47%), any leucopoenia 1.17% (95% CI 0.16-2.80%), any neutropenia 1.77% (95% CI 0.33-4.00%), and any thrombocytopenia 0.19% (95% CI 0.00-0.86%). Four cases of severe anaemia were reported, as defined by authors, along with three cases of severe neutropenia. No cases of severe leucopoenia, severe thrombocytopenia or pancytopenia were reported.. Cytopenias are an uncommon side effect of low-dose MTX with folic acid supplementation among RA patients. Further research is needed to reach a more precise estimate.

Topics: Anemia; Antirheumatic Agents; Arthritis, Rheumatoid; Folic Acid; Humans; Leucovorin; Leukopenia; Methotrexate; Neutropenia; Pancytopenia; Randomized Controlled Trials as Topic; Rheumatic Diseases; Severity of Illness Index; Thrombocytopenia; Vitamin B Complex

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

A 67-year-old man was diagnosed with pulmonary metastasis from advanced transverse colon cancer. Thus, a local resection was performed. Adjuvant chemotherapy with mFOLFOX6 was started. Sixteen courses were carried out without problems. However, he complained of chills and chest discomfort 2 hours after beginning the 17th course of chemotherapy. Laboratory data showed remarkable thrombocytopenia, and platelet-associated IgG level was high. After administration of steroids and platelet transfusions, the platelet count improved. Therefore, we diagnosed drug-induced thrombocytopenia resulting from sensitivity to oxaliplatin (L-OHP). Since then, sLV5FU2 therapy was started, and the patient received the whole adjuvant chemotherapy without problems. Thrombocytopenia resulting from sensitivity to L-OHP is a relatively rare side effect. We herein report this case with a review of the relevant literature.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colectomy; Colon, Transverse; Colonic Neoplasms; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Organoplatinum Compounds; Oxaliplatin; Platelet Transfusion; Pneumonectomy; Thrombocytopenia

Six randomized phase II and III trials have investigated the role of oxaliplatin (OX) in combination with capecitabine (CAP) or infusional fluorouracil (FU) in metastatic colorectal cancer. This meta-analysis compared the efficacy of CAP/OX compared with infusional FU/OX.. This analysis compared all published CAP/OX versus infusional FU/OX regimens. A total of 3,494 patients (FU, n = 1,737; CAP, n = 1,757) were analyzed for response rate (RR), progression-free (PFS), overall survival (OS), and toxicity.. The fixed-effect pooled estimate for RR showed higher RR for FU-based regimens (Odds ratio [OR] = 0.85; 95% CI, 0.74 to 0.97; P = .02) whereas the analysis of chemotherapy-only trials, excluding the bevacizumab containing NO16966 and TREE 2 trials, led to an OR of 0.74 (95% CI, 0.60 to 0.92; P = .007). However, for PFS (hazard ratio [HR] = 1.04; 95% CI, 0.96 to 1.12; P = .17) and OS (HR = 1.04; 95% CI, 0.95 to 1.12; P = .41) all models suggested similar outcome within the range of noninferiority. Grade 3/4 toxicities (thrombocytopenia-HR = 2.07, 95% CI, 1.42 to 3.03; P < .0002; diarrhea-HR = 1.34; 95% CI, 1.08 to 1.66; P < .0009; and grade 2/3 hand-foot-syndrome [HFS]-HR = 3.54; 95% CI, 2.07 to 6.05; P < .00001) were less prominent with FU-based regimens whereas neutropenia (HR = 0.15; 95% CI, 0.11 to 0.19; P < .00001) was lower in the CAP regimens.. The combination of CAP and OX resulted in lower RR, but this did not affect PFS and OS, which were similar in both treatment arms. The toxicity analysis showed the characteristic toxicity of each of the different FU schedules, with thrombocytopenia and HFS consistently more prominent in the CAP regimens.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Randomized Controlled Trials as Topic; Survival Rate; Thrombocytopenia; Vitamin B Complex

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

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

Although CRC is the third most commonly diagnosed cancer in the United States, second-line CRC treatment is limited. In this trial we examined the efficacy and safety of linifanib, an oral, potent, selective tyrosine kinase inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptor families, with mFOLFOX6, compared with bevacizumab and mFOLFOX6, in previously treated metastatic CRC.. One hundred forty-eight patients with advanced CRC previously treated with fluoropyrimidine or irinotecan received bevacizumab (10 mg/kg, intravenous), low-dose linifanib (7.5 mg), or high-dose linifanib (12.5 mg), with mFOLFOX6. The primary end point was progression-free survival (PFS). Secondary objectives included overall survival (OS), objective response rate (ORR), and safety.. No statistically significant differences in PFS occurred between bevacizumab and linifanib doses (low, hazard ratio [HR], 1.453 [95% confidence interval [CI], 0.830-2.539]; high, HR, 1.257 [95% CI, 0.672-2.351]). Median OS values were similar for bevacizumab and high-dose linifanib (bevacizumab, 16.5 months [95% CI, 13.0-not available]; high-dose linifanib, 16.4 months [95% CI, 11.9-21.7]; low-dose linifanib, 12.0 months [95% CI, 10.1-13.0]). ORRs were similar (bevacizumab, 34.7% [95% CI, 21.7-49.6]; low-dose linifanib, 24.0% [95% CI, 13.1-38.2]; high-dose linifanib, 22.4% [95% CI, 11.8-36.6]). Median cycles of 5-fluorouracil were reduced in the linifanib arms, versus the bevacizumab arm. Grade 3/4 adverse event occurrences were more frequent with linifanib. Palmar-plantar erythrodysesthesia, hypothyroidism, and thrombocytopenia were more common with high-dose linifanib than bevacizumab.. Combining linifanib with mFOLFOX6 as a second-line treatment for metastatic CRC did not improve PFS, radiographic findings, or duration of response versus bevacizumab and mFOLFOX6.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; Disease-Free Survival; Female; Fluorouracil; Hand-Foot Syndrome; Humans; Hypothyroidism; Indazoles; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Phenylurea Compounds; Survival Rate; Thrombocytopenia; Young Adult

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 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

To compare the efficacy and toxicity of capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/leucovorin (5-Fu/LV) plus oxaliplatin (FOLFOX4) regimens as adjuvant chemotherapy for stage III colorectal cancer.. The clinicopathological data of 118 patients with stage III colorectal cancer were studied retrospectively. The patients were assigned to receive either FOLFOX4 regimen (n = 76) or XELOX regimen (n = 42). 3-year disease-free survival (DFS) and adverse events as end points were compared between the two groups.. The number of patients that failed to finish 8 cycles was higher in FOLFOX4 group (28 vs. 8, P = 0.044). There was no significant difference for 3-year DFS and all grades adverse events between the two groups. However, the FOLFOX4 group showed more grade 3/4 neutropenia (31.6% vs. 14.3%, P = 0.039) and central venous catheter-associated complication (11.8% vs. 4.8%, P = 0.205), while XELOX showed more grade 3/4 thrombocytopenia (19.0% vs. 6.6%, P = 0.038) and hand-foot syndrome (11.9% vs. 1.3%, P = 0.012).. The results of this analysis indicate that XELOX and FOLFOX4 regimens have very similar efficacy as an adjuvant chemotherapy for stage III colon cancer, but XELOX may be safer than FOLFOX4.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Colorectal Neoplasms; Deoxycytidine; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Foot Dermatoses; Hand Dermatoses; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Oxaloacetates; Retrospective Studies; Syndrome; Thrombocytopenia

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

To investigate the efficiency, time to progression (TTP), overall survival (OS) and toxicity of epirubicin combined with DDP and 5-Fu (PELF regimen) for the treatment of advanced gastric cancer.. Totally, 101 patients with histopathologically confirmed advanced gastric cancer were enrolled and treated with PELF regimen in this study. Among them, 37 cases received adjuvant chemotherapy after R0 resection and 64 cases only received palliative chemotherapy without surgical resection. The regimen comprised of intravenous (i.v.) administration of epirubicin 50-80 mg/m2 for palliative chemotherapy or 40-50 mg/m2 for postoperative adjuvant chemotherapy on D1; i.v. infusion of cisplatin 10-20 mg/m2 in 2 hours on D1-D5; i.v. infusion of 5-Fu 425-600 mg/m2 for palliative chemotherapy or 425-500 mg/m2 for adjuvant chemotherapy in 4 hours for 5 days or continuous infusion for 120 hours; i.v. infusion of leucovorin (LV) 100-200 mg/m2 in 2 hours on D1-D5. This regimen was repeated every 3 to 4 weeks, and the first evaluation was done after two cycles.. Of the 37 patients who received adjuvant chemotherapy after R0 resection, 17 were still alive without recurrence, while 19 died of the disease. The median disease free survival time was 36.1 months and 5-year survival rate was 36.0%. Among the 64 cases who received only palliative chemotherapy, 47 patients were treated with this regimen as a first-line therapy and 34 patients were evaluable for response. The overall response rate was 26.5%, median time to progression (TTP) and overall survival (OS) was 6.6 and 13.7 months, respectively. Of the 17 patients who received this regimen as a second-line therapy, 10 were evaluable with an overall response rate of 20.0%. The median time to progression (TTP) in patients of this group was 5.1 months and median overall survival (OS) was 8.9 months. All the 101 patients were assessable for toxicity according to WHO criteria. The rate of grade 3 or 4 neutropenia, anemia and thromobocytopenia was 19.8%, 1.0% and 2.0%, respectively.. The regimen of epirubicin combined with DDP and 5-Fu is effective, well tolerable and safe for advanced gastric cancer patients either as adjuvant or as palliative therapy.

Topics: Adenocarcinoma; Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Disease Progression; Disease-Free Survival; Epirubicin; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Neutropenia; Palliative Care; Retrospective Studies; Stomach Neoplasms; Survival Rate; Thrombocytopenia

Combination therapies of fluorouracil (FU) with irinotecan (CPT-11) and docetaxel plus cisplatin have been proven to be active in metastatic gastric cancer. In this paper, we present the results of a phase III trial in which these two combinations given sequentially were compared to mitomycin C (MMC) monochemotherapy in an adjuvant setting.. 169 patients with radically resected gastric cancer were randomized to receive CPT-11 (180 mg/m2 day 1), leucovorin (100 mg/m2 days 1-2), FU (400-600 mg/m2 days 1-2, q 14; for four cycles; FOLFIRI regimen), followed by docetaxel (85 mg/m2 day 1), cisplatin (75 mg/m2 day 1, q 21; for three cycles; arm A), or MMC (8 mg/m2 days 1-2 as 2-hour infusion, q 42; for four cycles; arm B). All patients had histologically confirmed gastric carcinoma with nodal positivity or pT3/4. A total of 166 patients (85 in arm A and 81 in arm B) were treated. Adjuvant treatment was completed in 76% of the patients in arm A and in 70% of the patients in arm B. The main grade 3/4 side effects recorded were neutropenia in 35%, with only 1 febrile patient, and diarrhea in 11% in arm A, and thrombocytopenia in 10% and neutropenia in 7% in arm B. The FOLFIRI regimen and docetaxel/cisplatin given in sequence was well tolerated and feasible in adjuvant setting. This sequence treatment currently represents the experimental arm of an ongoing multicenter trial.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Cisplatin; Diarrhea; Digestive System Surgical Procedures; Disease-Free Survival; Docetaxel; Drug Administration Schedule; Feasibility Studies; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Mitomycin; Neutropenia; Prospective Studies; Stomach Neoplasms; Survival Rate; Taxoids; Thrombocytopenia; Treatment Outcome

The present study was conducted to evaluate the efficacy and safety of the combination of Oxaliplatin, Leucovorin and 5-FU as second line therapy, following relapse to Gemcitabine, in patients with advanced adenocarcinoma of the pancreas.. Patients with advanced pancreatic cancer previously treated with Gemcitabine were included in the study. All patients had histologically or cytologically confirmed adenocarcinoma of the pancreas that was unresectable, locally advanced or metastatic. Treatment consisted of Oxaliplatin 50 mg/m(2) (2-hour iv infusion), followed by Leucovorin 50 mg/m(2) (i.v. bolus) and 500 mg/m(2) 5-FU (1-hour iv infusion), administered weekly, until unacceptable toxicity or disease progression. Objective tumour response and toxicity were evaluated according to World Health Organisation (WHO) criteria.. A total of 30 patients, 20 men and 10 women, median age 63 years (range 52-71 years) and Karnofsky Performance Status (PS) of > or =50 entered the study. The majority of patients (96%) had locally advanced disease. A total of 380 doses of chemotherapy were delivered, a median of 12 doses per patient. Partial responses were observed in 7 patients (PR 23.3%), stable disease in 9 (SD 30.0%), while 14 patients progressed (PD 46.7%). Improved PS was observed in 18 (42.8%) patients. Patients that had responded to first-line Gemcitabine treatment were found more likely to respond or stabilize their disease with second-line treatment. The median duration of response was 22 weeks, and median overall survival was 25 weeks, Grade 3/4 toxicity expressed per chemotherapy dose included leukopenia 16%, anemia 3.2%, thrombocytopenia 3.2%, diarrhea 14.2%, fatigue 16.1% and neurotoxicity 4.2%. Eight patients (27%) suffered a febrile neutropenic event managed successfully with oral antibiotic home therapy, while 17 patients required G-CSF support. There were no treatment related deaths.. The combination of Oxaliplatin, Leucovorin and 5-FU was tolerated with manageable toxicity, offering encouraging activity as second-line treatment of patients with advanced or metastatic pancreatic adenocarcinoma, previously treated with Gemcitabine. Additional studies are warranted with this regimen in Gemcitabine relapsed pancreatic cancer patients.

Topics: Adenocarcinoma; Aged; Anemia; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Female; Fluorouracil; Gemcitabine; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Leukopenia; Lymphatic Metastasis; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Pancreatic Neoplasms; Prognosis; Salvage Therapy; Survival Analysis; Thrombocytopenia

Standard chemotherapy for advanced gastric cancer remains undefined. Phase II trials show that taxol is effective in treating advanced gastric cancer. This multi-center prospective open randomized controlled study was to compare the efficacy of Taxol plus calcium folinate (CF)/5-fluorouracil (5-FU), Taxol plus oxaliplatin (OXA), and CF/5-FU plus cisplatin (DDP) on advanced gastric cancer, and analyze their toxicities.. Patients with measurable unresectable and/or metastatic gastric carcinoma were randomized into CF/5-FU+DDP (control), CF/5-FU + Taxol, and Taxol + OXA groups, and received up to 8 cycles of chemotherapy. Treatment efficacy and adverse events were evaluated according to WHO criteria.. A total of 180 patients were enrolled from May 2002 to May 2004, and randomized into the 3 groups; each group contained 60 patients. Of the 180 patients, 14 received 2 cycles of chemotherapy, 49 received 4 cycles, and 103 received 8 cycles. Treatment outcomes of 166 cases were evaluable. The response rate (RR) of naive patients or the patients with retroperitoneal lymph node metastasis was significantly higher in CF/5-FU+Taxol and Taxol+OXA groups than in control group (50.00% and 80.00% vs. 20.75%, P<0.05; 65.96% and 85.71% vs. 36.36%, P<0.05). But the RR of the patients with liver metastasis was similar among the 3 groups (28.57% and 39.13% vs. 34.62%, P>0.05). The occurrence rates of nausea/vomiting, anepithymia, stomatitis, and kidney damage were lower in study groups than in control group, but the occurrence rates of myelosuppression and peripheral nerve damage were higher in study groups than in control group. Allergic response occurred in 7 (5.88%) patients in study group, and 3 (2.52%) of them were serious. There was no treatment-related death.. Despite its hematotoxicity, the treatment efficacy of Taxol-based combination regimens on advanced gastric cancer is better than that of CF/5-FU + DDP regimen with tolerable toxicities. We recommend Taxol-based combination regimens as first-line regimens for advanced gastric cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Paclitaxel; Prospective Studies; Remission Induction; Stomach Neoplasms; Thrombocytopenia

The aim of the present study was to evaluate the role of a weekly preoperative chemotherapy in locally advanced, unresectable gastric cancer. In all, 82 patients with an Eastern Oncology Cooperative Group PS

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Administration Schedule; Epirubicin; Female; Filgrastim; Fluorouracil; Glutathione; Granulocyte Colony-Stimulating Factor; Humans; Leucovorin; Leukopenia; Levoleucovorin; Male; Middle Aged; Neoadjuvant Therapy; Recombinant Proteins; Stomach Neoplasms; Thrombocytopenia; Treatment Outcome

To investigate the efficacy and safety of combining weekly oxaliplatin with weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and folinic acid (FA) in treatment of patients with advanced gastric cancer. Patients with histologically confirmed, locally advanced or recurrent/metastatic gastric cancer were studied. Oxaliplatin 65 mg m(-2) 2-h intravenous infusion, and 5-FU 2600 mg m(-2) plus FA 300 mg m(-2) 24-h intravenous infusion, were given on days 1 and 8, repeated every 3 weeks. Between January 2001 through January 2002, 55 patients were enrolled. The median age was 64 years (range: 22-75). In all, 52 patients (94.5%) had recurrent or metastatic disease and three patients had locally advanced disease. Among 50 patients evaluable for tumour response, 28 patients achieved partial response, with an overall response rate of 56% (95% confidence interval (CI): 41.8-70.3%). All 55 patients were evaluated for survival and toxicities. Median time to progression and overall survival were 5.2 and 10.0 months, respectively, during median follow-up time of 24.0 months. Major grades 3-4 toxicities were neutropenia in 23 cycles (7.1%) and thrombocytopenia in 16 cycles (5.0%). Treatment was discontinued for treatment-related toxicities in nine patients (16.4%), of whom eight were due to oxaliplatin-related neurotoxicity. One patient (1.8%) died of neutropenic sepsis. This oxaliplatin-containing regimen is effective in the treatment of advanced gastric cancer. Except for neurotoxicity that often develops after prolonged use of oxaliplatin, the regimen is well tolerated.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Nervous System; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms; Survival Analysis; Thrombocytopenia; Treatment Outcome

The purpose of this study was to evaluate the efficacy and toxicity of oxaliplatin plus 5-fluorouracil (5-FU) and leucovorin (LV) in patients with metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes.. Fifty anthracycline- and taxane-pretreated MBC patients were treated with oxaliplatin 85 mg/m(2) as a 2-h infusion on day 1, LV 200 mg/m(2)/day as a 2-h infusion followed by bolus 5-FU 400 mg/m(2)/day and a 22-h infusion of 5-FU 600 mg/m(2)/day for 2 consecutive days. Treatment was repeated every 3 weeks. Patients were evaluated for response every two cycles.. The median age was 51 years (range 34-75). Twenty patients (40%) had received three or more chemotherapeutic regimens, 64% had three or four metastatic sites and 78% had visceral metastases. All patients had prior exposure to anthracyclines and taxanes. Based on an intention-to-treat analysis, one patient (2%) achieved a complete response and 16 (32%) a partial response, for a 34% overall response rate. Twenty-one patients (42%) had stable disease and 12 (24%) progressive disease. The median time to tumor progression was 5.3 months (range 0.5-12.8) and the median overall survival was 12.3 months (range 0.5-19.2). Toxicity was mild to moderate. Grade 3/4 neutropenia and thrombocytopenia occurred in 32% and 18%, respectively. Febrile neutropenia was experienced by three patients (6%), who were successfully treated. Grade 3/4 neurotoxicity was reported in 14% of the patients and gradually declined after treatment discontinuation. Cycle delays were reported in 28% of patients and dose reductions in 26%. Alopecia, nausea-vomiting, diarrhea and mucositis were not significant. There were no treatment-related deaths.. The combination of oxaliplatin plus 5-FU/LV seems to be an active regimen in patients with MBC and prior exposure to anthracyclines and taxanes with a good safety profile. The incidence of severe toxicity was quite low and the compliance of patients to the treatment was satisfactory. The results obtained with this regimen could be considered encouraging in this heavily pretreated group of breast cancer patients with a high incidence of visceral metastases.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Disease Progression; Female; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Middle Aged; Nervous System; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Patient Compliance; Thrombocytopenia; Treatment Outcome

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

To evaluate the efficacy and safety profile of oral tegafur-uracil (tegafur combined with uracil in a molar of 1:4 ratio) plus leucovorin (LV) in patients with advanced biliary tract carcinoma (BTC).. Sixteen chemotherapy-naïve patients (nine males and seven females with a median age of 58.0 years) with BTC were prospectively enrolled in this study. The dose of tegafur-uracil (UFUR; TTY Biopharm Co. Ltd, Taipei, Taiwan) was 300 mg/m(2)/d (according to the dose of tegafur) and LV was 60 mg/day on day 1-28, followed by a 1-week break. The site of primary tumor included 10 intrahepatic cholangiocarcinomas (CC), one perihilar CC, four gallbladder cancers and one periampullar cancer. Fourteen patients were evaluated for tumor response.. No objective complete or partial responses were observed. Two patients had stable disease and 12 patients had disease progression. The median time to progression was 68 days (8-159 days) and the median survival time was 155 days (69-570 days). Sixteen patients were evaluable for toxicity. Grade III/IV toxicities were found in two patients only; one patient had grade III thrombocytopenia and one patient stopped therapy early due to grade IV diarrhea.. Oral tegafur-uracil plus LV is well tolerated but ineffective in patients with advanced BTC.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Drug Administration Schedule; Female; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Survival Analysis; Tegafur; Thrombocytopenia; Uracil

Since preclinical studies have shown more than additive cytotoxicity and DNA damage with the combination of gemcitabine and 5-fluoro-2'-deoxyuridine (FUDR), we studied this combination in a phase I trial.. Gemcitabine alone was given in cycle 1 as a 24-h, 2-h or 1-h i.v. infusion weekly for 3 of 4 weeks; if tolerated, a 24-h i.v. infusion of FUDR was added with oral leucovorin. The cycle was aborted for grade 3 thrombocytopenia, grade 4 neutropenia, and grade 2 or worse nonhematologic toxicity.. During cycle 1, six of eight patients who received 150 or 100 mg/m2 over 24 h had dose-limiting neutropenia, thrombocytopenia, fatigue or mucositis. Six of seven patients treated with 1000 mg/m2 over 2 h required a gemcitabine dose reduction for cycle 2 (thrombocytopenia, neutropenia, fatigue). Of 25 assessable patients who received gemcitabine 1000 mg/m2 over 1 h, 7 did not complete cycle 1 due to thrombocytopenia (n=6) or diarrhea (n=1). Of 42 patients entered, 27 received at least one course of gemcitabine/FUDR (5-19.5 mg/m2 over 24 h) without appreciable toxicity. Due to a shortage of FUDR, the protocol was closed early. Gemcitabine plasma concentrations averaged 0.061 micro M (24 h), 16.3 micro M (2 h), and 31.9 micro M (1 h). In 21 paired bone marrow mononuclear cell samples obtained before treatment and during FUDR infusion, thymidylate synthase ternary complex was only seen during FUDR infusion.. Gemcitabine 100-150 mg/m2 over 24 h was poorly tolerated, whereas toxicity was acceptable with 800-1000 mg/m2 over 1 h. Inhibition of the target enzyme was demonstrated at all FUDR doses.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Drug Administration Schedule; Female; Floxuridine; Gemcitabine; Humans; Infusions, Intravenous; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Neoplasms; Neutropenia; Ribonucleotide Reductases; Thrombocytopenia

Unresectable biliary tract carcinoma (BTC) is associated with a very poor prognosis. To improve efficacy and tolerance of the 5-fluorouracil (5-FU)/cisplatin combination in BTC, we designed a new therapeutic schedule, the LV5FU2-P regimen.. Twenty-nine patients with advanced or metastatic BTC were prospectively enrolled in the study. The treatment (LV5FU2-P regimen) consisted of a biweekly administration of a 2-h infusion of leucovorin 200 mg/m(2), a 400 mg/m(2) bolus of 5-FU followed by a 22-h continuous infusion of 600 mg/m(2) 5-FU on two consecutive days and cisplatin 50 mg/m(2) on day 2. Clinical symptoms, performance and weight changes were monitored.. Objective responses were observed in 10 patients (34%) (95% confidence interval 23% to 45%) including one complete response and nine partial responses (stabilization 38%, progression 28%). Median progression-free survival and overall survival were 6.5 and 9.5 months, respectively. Weight gain was observed in 45% of patients and performance status improved in 60%. One patient had a grade 4 thrombocytopenia, and grade 3 toxicity occurred in 41% of patients. There were no treatment-related deaths.. This study, one of the largest phase II trials performed for this disease, shows that the LV5FU2-P regimen is an active and well-tolerated chemotherapy for advanced and metastatic BTC.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Cholangiocarcinoma; Cisplatin; Female; Fluorouracil; Gastrointestinal Diseases; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neutropenia; Prospective Studies; Survival Rate; Thrombocytopenia; Treatment Outcome

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

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 use of oral chemotherapeutic agents in chemoradiotherapy provides several advantages. Doxifluridine, an oral 5-FU prodrug, has been shown to be effective in colorectal cancer. We attempted a Phase II trial of preoperative chemoradiotherapy with doxifluridine plus a low-dose oral leucovorin in unresectable primary rectal cancer patients. In this study, toxicity and efficacy were evaluated.. There were 23 patients with primary unresectable rectal cancer in this trial, 21 of whom were available for analysis. The patients were treated with oral doxifluridine (900 mg/day) plus oral leucovorin (30 mg/day) from days 1 to 35, and pelvic radiation of 45 Gy over 5 weeks. Surgical resection was performed 5-6 weeks after the treatment.. Acute toxicity involved thrombocytopenia, nausea/vomiting, diarrhea, and skin reaction. All were in Grade 1/2, except diarrhea, which was not only the most frequent (7 patients, 33.3%), but also the only toxicity of Grade 3 (2 patients). The clinical tumor response was shown in 5 patients (23.8%) as a complete response and 13 patients (61.9%) as a partial response. A complete resection with negative resection margin was done in 18 patients (85.7%), in 2 of whom a pathologic complete response was shown (9.5%). The overall downstaging rate in the T- and N-stage groupings was 71.4% (15 patients).. This study demonstrated the efficacy and low toxicity of chemoradiotherapy with doxifluridine. Currently, a Phase III randomized trial of chemoradiotherapy is ongoing at our institute to compare the therapeutic efficacy of oral 5-FU with respect to i.v. 5-FU in locally advanced and unresectable rectal cancer.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Diarrhea; Female; Floxuridine; Humans; Leucovorin; Male; Middle Aged; Preoperative Care; Radiotherapy; Rectal Neoplasms; Thrombocytopenia

The aim of the study was to evaluate the effectiveness and safety of a combined treatment modality including systemic chemotherapy with 5-fluorouracil (FU), leucovorin, cisplatin and external beam radiotherapy in patients with locally advanced pancreatic cancer. Systemic chemotherapy consisted of FU 400 mg m(-2) and leucovorin 20 mg m(-2) both given as intravenous bolus injection on days 1-4, plus cisplatin 20 mg m(-2) administered as 90-min infusion on days 1-4. Treatment courses were repeated every 4 weeks x 6 unless prior evidence of progressive disease. Radiation therapy using megavolt irradiation of > or = 6 MV photons with a 3- or 4-field technique was delivered during the second and third chemotherapy course, that was reduced in dose by 25%. Between October 1994 and July 1996, a total of 38 patients were entered onto this trial, all of whom were assessable for toxicity and survival. Eighteen of these (47%) had objective remissions to combined radiochemotherapy, including four CR (11%), 13 (34%) had stable disease and seven patients (18%) showed tumour progression during treatment. The median progression-free interval of the entire study population was 10 months (range 3-32), and median overall survival was 14.0 months (range 3-45+ months); 53% of all patients were alive at 12 months, and 18% of patients were alive at 24 months respectively. Severe haematological side-effects comprised neutropenia in 18%, thrombocytopenia in 8% and anaemia in 11%. The most frequent non-haematological side-effects were nausea/vomiting (WHO grade 3: 18%), and diarrhoea (grade 3: 13%). This combined radiochemotherapy regimen was tolerable and effective in patients with locally advanced pancreatic cancer. Since therapeutic results, in fact, compare favourably with other series, including surgical treatment of potentially resectable tumours, further evaluation of combined treatment modalities in the neoadjuvant setting seems warranted.

Topics: Adenocarcinoma; Adult; Aged; Agranulocytosis; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neutropenia; Pancreatic Neoplasms; Radiotherapy Dosage; Thrombocytopenia

The objective of this phase II prospective study was to determine the efficacy and the toxicity of a new schedule of neoadjuvant chemotherapy in locally advanced squamous cell carcinomas of the head and neck (SCCHN). Thirty-three patients were included in this study (13 stage III and 20 stage IV). Cisplatin (CDDP: 35 mg/m2), 5-fluorouracil (FU: 2 g/m2) and folinic acid (FA: 500 mg/m2) were administered by continuous i.v. infusion for 24 h, once every 7 days. Six cycles of neoadjuvant chemotherapy were planned before definitive locoregional treatment. A total of 195 cycles were analysed for toxicity: mucositis was observed in 11/195 cycles; 12/195 showed diarrhea and vomiting occurred in 10/195. The myelosuppression was low (neutropenia: 4/195, thrombopenia: 3/195). One treatment-related death was observed after grade IV neutropenia at the fourth cycle. Thirty-two patients were evaluated for response. The objective response rate was 87%, with 50% complete response (CR) and 37% partial response. Failure rate was 13% (stable disease). There was no progressive disease. Survival and DFS duration were significantly higher in cases of CR or in laryngeal localization. The average peak plasma levels for the 6 courses of CDDP, 5-FU, dl-FA and mTHF were 4.9+/-0.76 microM, 4.1+/-0.54 microM, 29.1+/-2.4 microM and 4.8+/-0.31 microM respectively. Therefore, the administration of the 3 drugs by a 24 h continuous i.v. infusion reached an efficient level for drug modulation. This new weekly schedule is as active as other standard therapy in the disease but significantly less toxic as neoadjuvant chemotherapy in advanced untreated SCCHN. With the low toxicities observed with this schedule, additional treatment (surgery and/or radiotherapy) is warranted to evaluate the impact on overall survival of SCCHN.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Disease-Free Survival; Female; Fluorouracil; Gastrointestinal Diseases; Head and Neck Neoplasms; Humans; Infusions, Intravenous; Leucovorin; Life Tables; Male; Middle Aged; Neoplasm Staging; Neutropenia; Remission Induction; Risk Factors; Stomatitis; Survival Analysis; Thrombocytopenia; Treatment Outcome

Patients with advanced gastric cancer unresponsive or progressing after PELF chemotherapy (5-fluorouracil, leucovorin, cisplatin and epidoxorubicin) received paclitaxel at the dose of 225 mg/m2 every 3 weeks, over 3 h infusion. Thirty-six patients entered the study, and all of them were evaluable for response and toxicity. Toxicity was mild: apart from alopecia, grade 3 toxicities were leukopenia and thrombocytopenia in six patients, and grade 2 neurotoxicity in seven patients. Eight patients (22.2%, 95% CI: 9-35%) achieved an objective response, with a median duration of 5 months. Median survival time for all patients was 8 months. In 16 of 36 patients (44%), treatment determined a significant relief of symptoms. Out-patient paclitaxel given over 3 h may be effective as salvage treatment in patients with advanced gastric cancer refractory to first line chemotherapy.

Topics: Adult; Aged; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Epirubicin; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Paclitaxel; Stomach Neoplasms; Survival Analysis; Thrombocytopenia; Time Factors

Our objective was to find the minimum dose of leucovorin (LV; 5-formyltetrahydrofolate) needed to potentially provide selective protection of normal tissue in patients with tumors resistant to methotrexate (MTX) by virtue of transport during prolonged therapy with high-dose trimetrexate (TMTX). Based upon the known daily requirement for folate, that tumors are often resistant to methotrexate via a transport-based mechanism, and that large doses of trimetrexate can be given with large doses of leucovorin for the treatment of patients with Pneumocystis carinii, a protocol was designed to find the minimum LV dose required to allow the administration of large doses of TMTX. Patients were treated in 28-day cycles consisting of 14 consecutive days of oral TMTX (45 mg/m2 every 12 h), followed by 14 days of rest. The dose of concurrent LV was started at 5 mg/m2 twice daily. Cohorts of patients received successive half doses of LV so long as three consecutive patients had less than or equal to grade 3 toxicity. Ten patients received 29 courses of therapy. The most common toxicities encountered were thrombocytopenia (38%), mucositis (14%), and neutropenia (10%). At a LV dose of 2.5 mg/m2, toxicities were consistently limited to less than or equal to grade 3 and only one episode of grade 4 hematological toxicity. Although there was marked interpatient variability, the minimally effective LV dose for selective protection seems to be 2.5 mg/m2. If tumors are resistant to methotrexate because of decreased transport of drug (and also folate), then the same pharmacological principle used to develop TMTX/LV for the treatment of P. carinii may be applied to treatment of some patients with cancer.

Topics: Adolescent; Adult; Antidotes; Antimetabolites, Antineoplastic; Child; Child, Preschool; Drug Interactions; Feasibility Studies; Humans; Infant; Leucovorin; Liver Function Tests; Mucous Membrane; Neoplasms; Thrombocytopenia; Treatment Outcome; Trimetrexate

Based on reports of substantial antitumor efficacy of the combination of mitoxantrone (DHAD), 5-fluorouracil (FU) and leucovorin (LV), a clinical trial was performed to attempt augmentation of the dose of DHAD with filgrastim support. The doses and schedules, all intravenous, were DHAD (total dose divided over days 1 and 2), level I, 16 mg/m2; II, 20 mg/m2; III, 24 mg/m2; IV, 32 mg/m2; and LV, 300 mg, followed by FU, 350 mg/m2, on days 1-3. Filgrastim was given at 5 micrograms/kg/day subcutaneously on days 4-13. The planned cycle length was 21 days. Three or 4 patients were to be entered at each dose level and the maximum tolerated dose (MTD) was defined as the dose immediately below that which resulted in 2 patients with dose-limiting toxicity (DLT) in cycle 1. Once an apparent MTD was identified, an additional 6 patients were to be entered. Twenty patients (pts) were entered: level I: 3 pts; II: 3 pts; III: 10 pts: IV: 4 pts. The major toxicity was found to be cumulative thrombocytopenia with platelet counts < or = 20,000/microL occurring after cycle 1 at all levels beyond level I and five pts (25%) were removed from treatment solely because of platelet toxicity. Additional serious toxicities included grade 4 stomatitis in one patient (level IV) and cardiac toxicity in 2 patients with prior doxorubicin exposure. Ten pts had measurable and 8 had evaluable disease, and in 17 pts assessed, 5 (29%) achieved an objective response. The response rates in this study are lower than reported in the literature for the combination of DHAD, 5FU, LV and this may be related to the fact that only 40% of the patients were removed from protocol treatment because of disease progression. On the basis of limited DHAD-dose augmentation, toxicities observed, and modest response rate, the filgrastim-supported DHAD, 5FU, LV regimen as utilized in this study cannot be recommended for further development for treatment of women with metastatic breast cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Filgrastim; Fluorouracil; Granulocyte Colony-Stimulating Factor; Humans; Leucovorin; Leukopenia; Middle Aged; Mitoxantrone; Neoplasm Metastasis; Patient Selection; Platelet Count; Recombinant Proteins; Survival Rate; Thrombocytopenia; Time Factors

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

We conducted a prospective randomized trial to evaluate the ability of the interleukin-3/granulocyte-macrophage colony-stimulating factor (GM-CSF) fusion protein, PIXY321, to ameliorate cumulative thrombocytopenia after multiple cycles of 5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide (FLAC) chemotherapy compared with GM-CSF in patients with advanced breast cancer. Fifty-three patients were randomized to receive either PIXY321. 375 microg/m2 twice a day subcutaneously, or GM-CSF, 250 microg/m2 daily subcutaneously after FLAC chemotherapy. PIXY321 was less well tolerated than GM-CSF, with more patients developing chills and local skin reactions and more patients stopping PIXY321 due to intolerance. While no difference in the neutrophil nadirs was seen with the two cytokines, the duration of the absolute neutrophil count less than 1,000/muL for all cycles was significantly longer with PIXY321 than with GM-CSF. Fifty percent of patients treated with multiple cycles of FLAC chemotherapy on both study arms developed dose-limiting thrombocytopenia. No differences in platelet nadirs, duration of thrombocytopenia, or need for platelet transfusions were observed with PIXY321 versus GM-CSF. The average delivered doses of FLAC chemotherapy were somewhat higher in the GM-CSF study arm. PIXY321 was not superior to GM-CSF in ameliorating the cumulative thrombocytopenia observed with multiple cycles of FLAC chemotherapy and was less well tolerated.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Humans; Immunologic Factors; Leucovorin; Middle Aged; Neutropenia; Platelet Transfusion; Prospective Studies; Thrombocytopenia; Treatment Outcome

Thirty patients with recurrent primary brain tumors were treated with a combination of 5-fluorouracil and leucovorin. There were three responses seen. Toxicity consisted of stomatitis, diarrhea, and hematological suppression. 5-fluorouracil and leucovorin would appear to be minimally effective in recurrent brain tumors.

Topics: Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Astrocytoma; Brain Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Oligodendroglioma; Recurrence; Stomatitis; Thrombocytopenia

Cumulative thrombocytopenia is a dose-limiting toxicity of dose-intensive chemotherapy for advanced breast cancer. In this phase I study, we have studied the hematologic toxicity associated with sequential interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF; molgramostim) administration after multiple cycles of FLAC (5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide) chemotherapy compared with that after concurrent cytokine administration or to each cytokine administered alone. Ninety-three patients with advanced breast cancer were treated with five cycles of FLAC chemotherapy and either IL-3 alone, GM-CSF alone, sequential IL-3 and GM-CSF administered by schedule A (5 days of IL-3 followed by 10 days of GM-CSF) or schedule B (9 days of IL-3 followed by 6 days of GM-CSF), or concurrent administration of IL-3 and GM-CSF for 15 days. Cohorts of patients were treated with one of four dose levels of IL-3 (1,2.5, 5, and 10 micrograms/kg) administered subcutaneously for each schedule of cytokine administration. The GM-CSF dose in all schedules was 5 micrograms/kg/day. Sequential IL-3 and GM-CSF (schedule B) was associated with higher platelet nadirs, shorter durations of platelet counts less than 50,000/microL, and the need for fewer platelet transfusions over five cycles of FLAC chemotherapy compared with concurrent cytokines, sequential IL-3 and GM-CSF schedule A, and GM-CSF alone. Concurrent IL-3 and GM-CSF was associated with unexpected platelet toxicity. The duration of granulocytopenia after FLAC chemotherapy was significantly worse with IL-3 alone compared with each of the GM-CSF-containing cytokine regimens. Although no cycle 1 maximum tolerated dose for IL-3 was defined in this study, 5 micrograms/kg was well tolerated over multiple cycles of therapy and is recommended for future studies. The data from this phase I study suggest that sequential IL-3 and GM-CSF with IL-3 administered for 9 days before beginning GM-CSF may be superior to shorter durations of IL-3 administered sequentially with GM-CSF, to concurrent IL-3 and GM-CSF, and to either colony-stimulating factor alone in ameliorating the cumulative hematologic toxicity associated with multiple cycles of FLAC chemotherapy. Additional studies of sequential IL-3 and GM-CSF are warranted.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Drug Interactions; Female; Fluorouracil; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunologic Factors; Injections, Subcutaneous; Interleukin-3; Leucovorin; Thrombocytopenia

In the EORTC lymphoma cooperative group, a randomized phase III study was done for patients with stage II, III, IV intermediate- and high-grade lymphoma. Eight courses of CHVmP-VB were compared to eight courses of ProMACE-MOPP. Response was evaluated after 8 courses. Of 430 patients entered, 346 were eligible for this first analysis. Additional radiotherapy was given at initial large masses or residual disease after three courses. Response rate was higher in the CHVmP-VB arm in comparison to the ProMACE-MOPP arm, 82% vs. 65% (p < 0.0005). In the ProMACE-MOPP arm, treatment had to be interrupted because of patient refusal in 7% of the patients. So far there has been no significant difference in freedom from progression at 5 years (49% vs. 47%), relapse-free survival (59% vs. 59%), or overall survival (55% vs. 49%). Patients with early response at 4 courses showed no better RFS in comparison with late responders between 4 and 8 courses. The International Index, based on age, stage, SLDH, performance status, and number of extranodal localizations showed a good prognostic significance in this series of patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Etoposide; Female; Humans; Leucovorin; Life Tables; Lymphoma, Non-Hodgkin; Male; Mechlorethamine; Methotrexate; Middle Aged; Neoplasm Staging; Prednisone; Procarbazine; Remission Induction; Survival Analysis; Teniposide; Thrombocytopenia; Treatment Outcome; Vincristine

Cerebral toxoplasmosis is the most frequent opportunistic infection in patients with acquired immune deficiency syndrome in France. We evaluated the effect of adding folic acid to the standard treatment (including pyrimethamine) on preventing induced cytopenia in order to determine the optimal dose.. From January to September 1990, pyrimethamine (50 mg 3 times per week) was given as primary prophylaxis against toxoplasmosis to 30 patients who were positive for human immunodeficiency virus (CDC classes II or II, CD4 counts < 200/mm3). The patients were randomly divided into three groups given 5, 25 and 0 mg folic acid 3 times per week. Associated treatments were the same in all patients (zidovudine 600 mg/d, pentamidine isethionate aerosol, 300 mg, once a month). Blood cell counts and lymphocyte subset counts were made on days 0, 30, 90 and 180.. Two patients were lost to follow-up and between day 90 and 180, 3 were excluded due to other opportunist infection and 1 due to zidovudine induced anaemia. Between the groups, there was no difference in haemoglobin level or cell counts on day 0. No haematologic toxicity was observed at day 90. Haemoglobin was significantly reduced in the control group (0 mg folic acid) on day 180 (mean haemoglobin on day 180, 13.8, 13.1 and 12.1 g/dl in groups 1, 2 and 3 respectively). No variation in polynuclear neutrophil counts was observed.. These findings suggest that folic acid has a moderate beneficial effect on preventing haematologic disease in patients treated with pyrimethamine. There was no observed dose effect.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Blood Cell Count; Hemoglobin A; Humans; Leucovorin; Prospective Studies; Pyrimethamine; Thrombocytopenia; Toxoplasmosis, Cerebral

38 patients with advanced oesophageal carcinoma were treated with intravenous (i.v.) folinic acid (300 mg/m2), 5-fluorouracil (500 mg/m2), etoposide (100 mg/m2), and cisplatin (30 mg/m2) (FLEP), on days 1, 2 and 3, every 22-28 days. 26 patients had locally advanced disease (LAD) and 12 had metastatic disease (M1). Oesophagectomy was planned for patients with LAD in case of tumour regression after chemotherapy, while patients with M1 disease received chemotherapy only. The overall remission rate was 45% (17/38) including four clinical and two pathologically confirmed complete remissions. 16 patients underwent oesophagectomy, 12 after response to FLEP, and 4 after FLEP and subsequent irradiation +/- 5-fluorouracil/mitomycin. Toxicity was mainly haematological, with WHO grade 3 and 4 leukocytopenia in 50% and thrombocytopenia in 31% of the patients. Two treatment-related deaths were observed; one due to chemotherapy and one postoperatively. Median survival time of LAD patients was 13 months, and actuarial 2-year survival was 31%. Patients with complete tumour resection after FLEP had a median survival time of 18 months and a 2-year survival rate of 42%. Median survival of M1 patients was 6 months. FLEP is an active combination for oesophageal cancer, especially when used preoperatively in LAD.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Esophageal Neoplasms; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Remission Induction; Thrombocytopenia; Treatment Outcome

The purpose of this prospective clinical trial was an attempt to find an effective and relatively non-toxic schedule for patients with metastatic breast cancer who decline to receive aggressive cytotoxic chemotherapy. A total of 36 patients with disseminated breast cancer were treated with mitoxantrone 8 mg/m2 intravenously (i.v.) day 1, folinic acid 400 mg/m2 in a 2-h i.v. infusion with 5-fluorouracil 500 mg/m2 as an i.v. bolus 1 h later, days 1 and 8 at 3-week intervals plus prednisone 20 mg/m2 orally daily with diminishing doses over several weeks. Objective regressions were observed in 24/36 (67%) patients, 9 being complete (25%). Responses were seen at all disease sites, mainly pleural/lung, bone and liver. The median duration of response was 8 months (range 4-25+) and the median survival 12 months (range 3-26+). Myelosuppression, mainly leucopenia and thrombocytopenia, was the major toxicity but without complications. Other toxicities included mild or moderate nausea and/or vomiting (50%), stomatitis (33%) and diarrhoea (11%). Alopecia was minimal. No cases of cardiotoxicity were detected. The substantial response rate obtained with this relatively well tolerated regimen against advanced breast cancer warrants its assessment in a larger number of patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Middle Aged; Mitoxantrone; Prednisone; Prognosis; Prospective Studies; Thrombocytopenia; Time Factors

38 patients with advanced breast adenocarcinoma were treated in a phase II study with 5-fluorouracil and high-dose folinic acid combined with cyclophosphamide and mitoxantrone. 6 patients had received prior chemotherapy for advanced disease, all with an anthracycline-containing regimen. Treatment was generally well tolerated. The most common side-effect was myelosuppression, with 1 toxic death due to leukopenia-related sepsis. 1 patient developed severe congestive heart failure 12 months from the end of therapy. 36 patients were evaluable for response. The overall response rate was 55%. Median duration of response was 8 months and median survival time was 16 months. This regimen warrants further investigations.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Drug Evaluation; Female; Fluorouracil; Heart Failure; Humans; Leucovorin; Leukopenia; Middle Aged; Mitoxantrone; Salvage Therapy; Thrombocytopenia

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Colorectal Neoplasms; Diarrhea; Fluorouracil; Humans; Leucovorin; Leukopenia; Methotrexate; Random Allocation; Thrombocytopenia

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

Fifty-three patients with metastatic osteogenic sarcoma were treated with vincristine, high-dose methotrexate with citrovorum factor rescue, and cisplatin. Metastases were surgically removed in most patients, either prior to chemotherapy or following initial response to therapy. Among 29 previously treated patients, responses to initial chemotherapy included two complete remissions, six partial remissions, and eight patients with stable disease. Twenty-three patients were disease-free, six for greater than 12 months. Toxicity was moderate, but usually reversible. There were two toxic deaths and one unexplained death 48 hours following a dose of cisplatin.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cisplatin; Clinical Trials as Topic; Combined Modality Therapy; Female; Humans; Kidney Diseases; Leucovorin; Male; Methotrexate; Neoplasm Metastasis; Neutropenia; Osteosarcoma; Thrombocytopenia; Time Factors; Vincristine

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

Posterior reversible encephalopathy syndrome is a clinical and imaging syndrome characterized by endothelial dysfunction, blood-brain barrier disruption, and vasogenic edema. The common clinical symptoms of posterior reversible encephalopathy syndrome include headache, altered consciousness, visual disturbances, and seizures, among which headache and seizures are the most common. The classic imaging patterns usually reveal vasogenic edema.. We describe the case of a middle-aged woman with gastric cancer. She was under treatment by fluorouracil, leucovorin, oxaliplatin, and docetaxel regimen and thrombocytopenia regimen after tumor progression, but developed unconsciousness, irritability, and headache shortly after initiation of treatment. Her magnetic resonance imaging in our hospital shows abnormal signals in bilateral frontal parietal occipital lobes with hyperintensities on T2-weighted magnetic resonance imaging and fluid-attenuated inversion recovery imaging, accompanied by the increased value of apparent diffusion coefficient. And T1-weighted images illustrate hypointense foci, with increased diffusion-weighted imaging signals.. After admission, she was treated to control blood pressure, reduce brain edema, expand blood vessels, improve consciousness, and symptomatic support treatment. 3 days after the onset of the disease, her headache symptoms and state of consciousness gradually improved, and her blood pressure can be controlled at about 130/80 mmHg.. This is the first report that posterior reversible encephalopathy syndrome is caused by a thrombocytopenia regimen, and our case highlights the pathogenic role of a thrombocytopenia regimen in posterior reversible encephalopathy syndrome. However, the association between the thrombocytopenia regimen and previous fluorouracil, leucovorin, oxaliplatin, and docetaxel regimens needs further study.

Topics: Calcium; Cisplatin; Docetaxel; Edema; Female; Fluorouracil; Headache; Humans; Leucovorin; Middle Aged; Oxaliplatin; Posterior Leukoencephalopathy Syndrome; Seizures; Thrombocytopenia

To describe the management and outcome of a dog following a 10-fold dosing error of vincristine.. A 2-year-old neutered female Toy Fox Terrier presenting for immune-mediated thrombocytopenia was administered an accidental overdose of vincristine (0.2 mg/kg [2.71 mg/m. This is the first report of the successful management of severe vincristine overdose in a dog. Therapy included the use of Tbo-filgrastim, folinic acid, and glutamic acid along with aggressive supportive care.

Topics: Animals; Dog Diseases; Dogs; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Female; Filgrastim; Glutamic Acid; Leucovorin; Thrombocytopenia; Vincristine

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

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

A 27-year-old woman with colon cancer and liver metastasis was referred to our hospital. Colectomy and colostomy were performed to improve her ileus. Following 13 sessions of oxaliplatin-based chemotherapy (OC) with mFOLFOX6 + bevacizumab, thrombocytopenia and frequent peristomal bleeding occurred. Computed tomography showed severe ascites, splenomegaly, significant collateral veins around the stoma, and severe stenosis of the hepatic veins (HV) and inferior vena cava (IVC). Ultrasound elastography showed high liver (and spleen) stiffness values. Repeated OC appeared to cause IVC stenosis as a result of worsening sinusoidal obstruction syndrome (SOS), and peristomal variceal bleeding. After ultrasound-guided percutaneous embolization, bleeding did not recur. Unfortunately, the patient died of liver dysfunction caused by severe SOS. The incidence of OC-induced SOS is reported to be about 50%; however, there is apparently no report of OC-induced HV and IVC stenosis, and in most cases, portal hypertension is improved after OC cessation. This is the first report of OC-induced severe HV and IVC stenosis resulting in refractory peristomal variceal bleeding and eventual death.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colonic Neoplasms; Constriction, Pathologic; Embolization, Therapeutic; Fatal Outcome; Female; Fluorouracil; Gastrointestinal Hemorrhage; Hepatic Veins; Humans; Leucovorin; Organoplatinum Compounds; Oxaliplatin; Surgical Stomas; Thrombocytopenia; Varicose Veins; Vena Cava, Inferior

Oxaliplatin-based chemotherapy can cause hepatic sinusoidal injury (HSI), portal hypertension, and splenic sequestration of platelets. Evidence suggests that bevacizumab may protect against HSI.. Two cohorts of metastatic colorectal cancer (CRC) were analyzed: a nonrandomized exploratory cohort of 184 patients treated at a single institution from 2003 to 2010 and a confirmatory cohort of 200 patients from a multi-institutional randomized trial (NO16966). All patients were treated with frontline fluoropyrimidine and oxaliplatin with or without bevacizumab. Changes in splenic volumes and platelet counts were compared by treatment, two-sided log-rank test.. In the exploratory cohort, the bevacizumab-treated patients (n = 138) compared with the nonbevacizumab-treated patients (n = 46) demonstrated a longer median time to splenic enlargement (≥30%, P = .02) and reduced rate of thrombocytopenia (<150 000/mm3, P = .04). In the confirmatory cohort (106 bevacizumab arm and 94 placebo arm), the median time to a spleen enlargement of 30% or more was 7.6 vs 5.4 (P = .01), and six-month cumulative incidence of thrombocytopenia (platelets < 100 000/mm3) was 19% vs 51% (P < .001) for bevacizumab compared with placebo. The development of an increasing spleen size was associated with the risk of either grade 1 or grade 2 thrombocytopenia (P < .001). The cumulative rate of grade 1 or grade 2 thrombocytopenia was statistically less in the bevacizumab arm, with six-month grade 2 thrombocytopenia rates of 4% vs 23% (P < .001). Patients with a large spleen prior to chemotherapy initiation appeared to be at highest risk of this toxicity.. In metastatic CRC, the addition of bevacizumab to oxaliplatin-based chemotherapy reduces the frequency of splenic enlargement and the rate of thrombocytopenia.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Chemical and Drug Induced Liver Injury; Clinical Trials, Phase III as Topic; Colorectal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Liver; Male; Middle Aged; Multicenter Studies as Topic; Neoplasm Metastasis; Organ Size; Organoplatinum Compounds; Oxaliplatin; Randomized Controlled Trials as Topic; Retrospective Studies; Spleen; Thrombocytopenia

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 purpose of this study was to evaluate the feasibility and safety of ambulatory high-dose methotrexate (HDMTX) administration with oral hydration, alkalinization, and leucovorin rescue. HDMTX (12 g/m) was given intravenously over 4 hours after urine alkalinization. Families and patients were instructed to continue ambulatory oral hydration and alkalinization to monitor urine pH and to adjust bicarbonate according to our institution's treatment algorithm. Clinical status and MTX levels were controlled every 24 hours, and oral leucovorin dose was adjusted accordingly.. From April 2007 to December 2010, 150 of 447 courses of HDMTX (31.4%) were given on an outpatient basis, and 91.2% were successfully completed. The main causes of failure were poor oral tolerance (n=6) and fever (n=4). Most patients (81%) had MTX levels of <10 μmol/L 24 hours post-HDMTX; only in 1 course the levels were >50 μmol/L (50.96 μmol/L). Neutropenia grade III/IV was observed in 18.3% of the courses, grade III/IV leukopenia in 2.7%, and grade III/IV thrombocytopenia and anemia in 4.7%. Around 39% were associated with grade III/IV hepatic toxicity (asymptomatic hypertransaminasemia), grade III-IV gastrointestinal toxicity (vomiting and diarrhea) (5%), grade III-IV mucositis (4%), and none of the patients developed renal toxicity.. Ambulatory HDMTX administration is feasible and safe in a population with poor resources in a developing country.

Topics: Adolescent; Algorithms; Ambulatory Care; Anemia; Antacids; Argentina; Chemical and Drug Induced Liver Injury; Child; Diarrhea; Female; Humans; Hydrogen-Ion Concentration; Leucovorin; Leukopenia; Male; Methotrexate; Mucositis; Neutropenia; Osteosarcoma; Retrospective Studies; Thrombocytopenia; Vomiting

To evaluate the outcomes and toxicity of concurrent full-dose gemcitabine and intensity-modulated radiation therapy (IMRT) for patients with borderline resectable and locally advanced pancreatic adenocarcinoma after induction chemotherapy.. From 2009 to 2012, 32 patients were treated with concurrent gemcitabine and IMRT for borderline resectable or locally advanced pancreatic adenocarcinoma. All patients received induction FOLFIRINOX or gemcitabine-based chemotherapy before chemoradiation. The radiotherapy volume was limited to the primary tumor, and the median dose was 55 Gy in 25 fractions. Gemcitabine was administered weekly during radiotherapy on days 1, 8, 22, and 29 at a median weekly dose of 800 mg/m².. Twenty-five patients had locally advanced disease and 7 had borderline resectable disease. The median follow-up time was 14.6 months. The median progression-free and overall survival were 13.9 and 23.1 months, with a trend toward improved overall survival for patients receiving induction FOLFIRINOX compared with gemcitabine-based therapy. A radiographic complete or partial response was achieved in 13 patients (41%), with 4 (13%) having complete radiographic responses. Surgical resection was performed in 10 patients (31%)--6 patients with locally advanced disease and 4 with borderline resectable disease. Grade 3/4 hematologic toxicity during and up to 6 weeks after chemoradiation occurred in 12 patients (38%); grade 3 nonhematologic toxicity occurred in 7 patients (22%), with no grade 4 or 5 toxicity. All patients completed their radiotherapy.. Concurrent full-dose gemcitabine and limited-field IMRT after induction chemotherapy for the treatment of borderline resectable and locally advanced pancreatic cancer is promising with acceptable toxicity rates.

Topics: Adenocarcinoma; Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Capecitabine; Chemoradiotherapy; Cisplatin; Cohort Studies; Deoxycytidine; Disease Progression; Duodenal Ulcer; Erlotinib Hydrochloride; Female; Fluorouracil; Gastrointestinal Diseases; Gemcitabine; Humans; Induction Chemotherapy; Irinotecan; Leucovorin; Male; Middle Aged; Multivariate Analysis; Neoadjuvant Therapy; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Pancreatectomy; Pancreatic Neoplasms; Proportional Hazards Models; Radiotherapy, Intensity-Modulated; Retrospective Studies; Thrombocytopenia; Treatment Outcome

Splenomegaly is a clinical surrogate of oxaliplatin-induced sinusoidal obstruction syndrome (SOS). We investigated development of splenomegaly and its association with treatment outcome and genetic polymorphisms following adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in colorectal cancer (CRC) patients.. Splenomegaly was determined by spleen volumetry using computed tomography images obtained before initiation of chemotherapy and after completion of adjuvant FOLFOX in CRC patients. Ten genetic polymorphisms in 4 SOS-related genes (VEGFA, MMP9, NOS3, and GSTP1) were analyzed using DNA from peripheral blood mononuclear cells.. Of 124 patients included, increase in spleen size was observed in 109 (87.9%). Median change was 31% (range, -42% to 168%). Patients with splenomegaly had more severe thrombocytopenia compared to patients without splenomegaly during the chemotherapy period (p < 0.0001). The cumulative dose of oxaliplatin and the lowest platelet count during the chemotherapy period were clinical factors associated with splenomegaly. However, no significant associations were found between genetic polymorphisms and development of splenomegaly. Disease-free survival was similar regardless of the development of splenomegaly.. Splenomegaly was frequently observed in patients receiving adjuvant FOLFOX and resulted in more severe thrombocytopenia but did not influence treatment outcome. Examined genetic polymorphisms did not predict development of splenomegaly.

Topics: Adult; Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colorectal Neoplasms; Disease-Free Survival; DNA; Female; Fluorouracil; Genotyping Techniques; Glutathione S-Transferase pi; Hepatectomy; Hepatic Veno-Occlusive Disease; Humans; Leucovorin; Leukocytes, Mononuclear; Liver Neoplasms; Male; Matrix Metalloproteinase 9; Middle Aged; Nitric Oxide Synthase Type III; Organoplatinum Compounds; Platelet Count; Polymorphism, Single Nucleotide; Retrospective Studies; Sequence Analysis, DNA; Splenomegaly; Thrombocytopenia; Tomography, X-Ray Computed; Treatment Outcome; Vascular Endothelial Growth Factor A

To quantify ensuing bone marrow (BM) suppression during postoperative chemotherapy resulting from preoperative chemoradiation (CRT) therapy for rectal cancer.. We retrospectively evaluated 35 patients treated with preoperative CRT followed by postoperative 5-Fluorouracil and oxaliplatin (OxF) chemotherapy for locally advanced rectal cancer. The pelvic bone marrow (PBM) was divided into ilium (IBM), lower pelvis (LPBM), and lumbosacrum (LSBM). Dose volume histograms (DVH) measured the mean doses and percentage of BM volume receiving between 5-40 Gy (i.e.: PBM-V5, LPBM-V5). The Wilcoxon signed rank tests evaluated the differences in absolute hematologic nadirs during neoadjuvant vs. adjuvant treatment. Logistic regressions evaluated the association between dosimetric parameters and ≥ grade 3 hematologic toxicity (HT3) and hematologic event (HE) defined as ≥ grade 2 HT and a dose reduction in OxF. Receiver Operator Characteristic (ROC) curves were constructed to determine optimal threshold values leading to HT3.. During OxF chemotherapy, 40.0% (n=14) and 48% (n=17) of rectal cancer patients experienced HT3 and HE, respectively. On multivariable logistic regression, increasing pelvic mean dose (PMD) and lower pelvis mean dose (LPMD) along with increasing PBM-V (25-40), LPBM-V25, and LPBM-V40 were significantly associated with HT3 and/or HE during postoperative chemotherapy. Exceeding ≥36.6 Gy to the PMD and ≥32.6 Gy to the LPMD strongly correlated with causing HT3 during postoperative chemotherapy.. Neoadjuvant RT for rectal cancer has lasting effects on the pelvic BM, which are demonstrable during adjuvant OxF. Sparing of the BM during preoperative CRT can aid in reducing significant hematologic adverse events and aid in tolerance of postoperative chemotherapy.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Marrow Diseases; Capecitabine; Chemoradiotherapy; Female; Fluorouracil; Humans; Ilium; Leucovorin; Leukopenia; Logistic Models; Lumbar Vertebrae; Male; Middle Aged; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Pelvic Bones; Preoperative Care; Rectal Neoplasms; Retrospective Studies; ROC Curve; Sacrum; Statistics, Nonparametric; Thrombocytopenia

There was performed a molecular genetic study of UGTlAl gene allelic variants polymorphism in patients with colorectal cancer who had had chemotherapy irinotecan-containing regimens FOLFIRI. Comparison of toxicity and the results of polymorphism of UGTlAl showed that dose-limiting hematologic and non-hematologic toxicities in patients with moderate and high risk of toxicity were higher (p = 0.050- 0.061) and the frequency of thrombocytopenia (p = 0.0257) and hyperbilirubinemia (p = 0.0439) were significantly higher compared to the low-risk group. Molecular genetic study of a complex examination of patients, which was planned to irinotecan should be performed to select the optimal dose and reduce the risk of toxicity of chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Dose-Response Relationship, Drug; Female; Fluorouracil; Glucuronosyltransferase; Humans; Hyperbilirubinemia; Incidence; Irinotecan; Leucovorin; Male; Middle Aged; Polymorphism, Genetic; Thrombocytopenia

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Phytogenic; Bevacizumab; Camptothecin; Colonic Neoplasms; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Middle Aged; Platelet Count; Thrombocytopenia

Chemotherapy-induced thrombocytopenia (CIT) is an important cause of morbitity in patients with cancer.. To investigate the effect of the baseline plasma D-dimer level, an important marker for thrombotic activity, on chemotherapy-induced thrombocytopenia in patients with stage III colon cancer.. A total of 43 (28 men) eligible patients were divided into two groups according to whether they exhibited chemotherapy-induced thrombocytopenia: Group 1 (n=21) and Group 2 (n=22). Comparison was made using demographic, histopathologic, and laboratory variables. Additionally, baseline plasma D-dimer levels underwent receiver operation characteristics curve analysis, and areas under the curve were calculated. Sensitivity, specificity, and positive and negative likelihood rates were then determined.. The incidence of chemotherapy-induced thrombocytopenia had a significant correlation with baseline platelet count (r=0.568, P=0.031) and baseline plasma D-dimer levels (r=0.617, P=0.036). When the cut-off point for the latter was set as 498 ng/mL, the area under the curve was 0.89 (95%CI: 0.74-0.93), the sensitivity was 91.4%, the specificity was 89.7%, the positive likelihood rate was 3.64 and the negative likelihood rate was 0.24 for chemotherapy-induced thrombocytopenia diagnosis.. The baseline level of plasma D-dimer could help to differentiate high- risk patients for chemotherapy-induced thrombocytopenia.

Topics: Adult; Analysis of Variance; Anemia; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Biomarkers; Colonic Neoplasms; Female; Fibrin Fibrinogen Degradation Products; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neutropenia; Organoplatinum Compounds; Pilot Projects; Platelet Count; Predictive Value of Tests; Retrospective Studies; ROC Curve; Statistics, Nonparametric; Thrombocytopenia

We report a case of advanced rectal cancer treated with chemotherapy, for which laparoscopic splenectomy had been effective for thrombocytopenia. A 56-year-old man suffered from advanced rectal cancer with multiple lung metastases. He underwent Hartmann's procedure and received chemotherapy with FOLFOX and FOLFIRI with bevacizumab. After 3 years and 2 months, he also suffered from splenomegaly and thrombocytopenia. Laparoscopic splenectomy produced and increased the thrombocyte count, allowing for a restart of chemotherapy. Oxaliplatin-based chemotherapy might produce hepatic sinusoid injury and induce splenomegaly owing to portal hypertension. Laparoscopic splenectomy seemed to be useful for treating thrombocytopenia, and allowed the continuation of chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Fatal Outcome; Fluorouracil; Humans; Laparoscopy; Leucovorin; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Splenectomy; Splenomegaly; Thrombocytopenia

Previous studies reported that oxaliplatin is associated with sinusoidal obstruction syndrome. However few reports on oxaliplatin induced liver fibrosis are found in the literature. Furthermore pathogenesis of liver fibrosis is not well known. We report a case of 45-yr-old Korean man in whom liver fibrosis with splenomegaly developed after 12 cycles of oxaliplatin based adjuvant chemotherapy for colon cancer (T4N2M0). Thorough history taking and serological examination revealed no evidence of chronic liver disease. Restaging CT scans demonstrated a good response to chemotherapy. Five month after chemotherapy, he underwent right hepatectomy due to isolated metastatic lesion. The liver parenchyma showed diffuse sinusoidal dilatation and centrilobular vein fibrosis with necrosis without steatosis. We could conclude that splenomegaly was due to perisinusoidal liver fibrosis and liver cell necrosis induced portal hypertension by oxaliplatin. In addition, to investigate the pathogenesis of liver fibrosis, immunohistochemical stains such as CD31 and α-smooth muscle actin (α-SMA) were conducted with control group. The immunohistochemical stains for CD31 and α-SMA were positive along the sinusoidal space in the patient, while negative in the control group. Chemotherapy with oxaliplatin induces liver fibrosis which should be kept in mind as a serious complication.

Topics: Actins; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Colonic Neoplasms; Fluorouracil; Humans; Hypertension, Portal; Immunohistochemistry; Leucovorin; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Platelet Endothelial Cell Adhesion Molecule-1; Splenomegaly; Thrombocytopenia; Tomography, X-Ray Computed

Oxaliplatin is effective in advanced colorectal cancer and is known to have relatively few side effects, such as hemolysis and renal toxicity. We report a case of acute kidney injury (AKI) after treatment with a combination of oxaliplatin, folinic acid and 5-fluorouracil or capecitabine. The patient developed acute renal failure, hemolytic anemia and thrombocytopenia after the 34th course of chemotherapy including oxaliplatin. A positive direct antiglobulin test and detection of immunoglobulin G and complement C3b and C3d on erythrocytes suggested the diagnosis of immune-related severe intravascular hemolytic anemia. She was successfully treated and recovered using plasma exchange, corticosteroids and hemodialysis therapy. Only seven other cases of AKI associated with oxaliplatin use have been reported to date. As in this case, acute hemolysis due to autoimmune mechanisms and subsequent AKI occurred suddenly after frequent use of oxaliplatin in four of those cases. We should be aware that oxaliplatin may cause sudden life-threatening hemolysis by drug-induced antibodies and subsequent AKI, even though oxaliplatin is frequently administered without side effects. This represents the first case report of AKI-related hemolysis due to oxaliplatin in Japan.

Topics: Acute Kidney Injury; Anemia, Hemolytic, Autoimmune; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Colonic Neoplasms; Deoxycytidine; Fluorouracil; Humans; Leucovorin; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Prednisone; Thrombocytopenia

A 25-year-old primigravida was diagnosed to be suffering from unruptured ectopic pregnancy. The serum β-human chorionic gonadotropin levels were 2851 mIU/l and the ectopic gestational sac was 2.7×2.7 cm without any fetal pole. It was decided to manage her by expectant therapy. But she received medical therapy with multidose methotrexate because of misinterpretation of expectant therapy as medical therapy. She suffered from methotrexate toxicity, which manifested as high-grade fever, vomiting, melena, oral ulcerations, pneumonitis, subconjunctival haemorrhages and skin pigmentation. She developed severe third space fluid collection and shock, which was mistaken for rupture ectopic gestation. Her haematological picture showed severe neutropaenia and thrombocytopaenia which confirmed the clinical picture to be due to methotrexate toxicity. She also developed septicaemia and candidal infection secondary to immunosuppression. She was managed in intensive care unit with ventilatory support, high-dose leucovorin and injection filgastrim. She responded well to the therapy with dramatic recovery in 4 days.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Therapeutic; Adult; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Leucovorin; Medical Errors; Methotrexate; Neutropenia; Pregnancy; Pregnancy, Ectopic; Recombinant Proteins; Respiration, Artificial; Sepsis; Shock; Thrombocytopenia; Vitamin B Complex

A 70-year-old woman underwent emergent clipping surgery for subarachnoid hemorrhage under general anesthesia. Her laboratory data showed thrombocytopenia (4.0 x 10(4) microl(-1)). She had taken prednisolone (3 mg x day(-1)) and methotrexate (MTX) (10 mg x week(-1)) for rheumatoid arthritis for the last 10 years. Anesthesia was induced with remifentanil as well as propofol, maintained with remifentanil and sevoflurane in oxygen. The operation was performed uneventfully without platelet transfusion. Since the cause of thrombocytopenia was suspected to be MTX, we started rescue therapy by calcium folinate postoperatively. Platelet count was normalized two days later (11.6 x 10(4) microl(-1)). One month after the operation, she was discharged uneventfully.

Topics: Aged; Anesthesia, General; Arthritis, Rheumatoid; Emergencies; Female; Humans; Immunosuppressive Agents; Intracranial Aneurysm; Leucovorin; Methotrexate; Piperidines; Platelet Transfusion; Postoperative Care; Propofol; Remifentanil; Subarachnoid Hemorrhage; Thrombocytopenia; Treatment Outcome; Vascular Surgical Procedures

We examined the feasibility of regimen selection for first-line irinotecan, 5-fluorouracil and leucovorin or oxaliplatin, 5-fluorouracil and leucovorin in Japanese patients with advanced colorectal cancer based on UDP-glucuronosyltransferase 1A1 genotype as well as physical status of patients related to diarrhea.. As first-line irinotecan, 5-fluorouracil and leucovorin is a little bit superior to oxaliplatin, 5-fluorouracil and leucovorin with respect to efficacy and toxicity, patients without risk factors of irinotecan-induced toxicity were first assigned to irinotecan, 5-fluorouracil and leucovorin. Patients with UDP-glucuronosyltransferase 1A1 28/ 28, 6/ 6, 28/ 6 or 28/ 27 and those with ascites, peritoneal dissemination or diarrhea first received oxaliplatin, 5-fluorouracil and leucovorin to avoid the irinotecan-induced neutropenia and diarrhea, respectively. We retrospectively evaluated the feasibility of this strategy by assessing toxicity and total progression-free survival in first- and subsequent second-line therapies in all patients studied.. In the first-line irinotecan, 5-fluorouracil and leucovorin (n = 61), Grade 4 neutropenia, febrile neutropenia and Grade 3 diarrhea occurred in 8.2, 3.3 and 3.3% of patients, respectively. In the first-line oxaliplatin, 5-fluorouracil and leucovorin (n = 26), Grade 4 neutropenia, febrile neutropenia, Grade 3 thrombocytopenia and Grade 3 neuropathy were observed in 11.5, 3.8, 3.8 and 7.7% of patients, respectively. In the second-line oxaliplatin, 5-fluorouracil and leucovorin (n = 38), Grade 3 diarrhea occurred in 2.6% of patients. In the second-line irinotecan monotherapy (n = 11), Grade 4 or febrile neutropenia occurred in 18% of patients and Grade 3 diarrhea in 9.1% of patients. In second-line S-1 (n = 9), Grade 3 anemia occurred in 2 patients. Median total progression-free survival in all 87 patients was 11.5 months.. Present regimen selection strategy would be feasible, since it causes less toxicity and similar efficacy comparing to previous studies. Determination of appropriate reduced dose in the second-line irinotecan monotherapy or other standard second-line therapy for patients with high-risk to irinotecan-induced toxicity might make this strategy more effective.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Asian People; Camptothecin; Colorectal Neoplasms; Diarrhea; Feasibility Studies; Female; Fluorouracil; Genotype; Glucuronosyltransferase; Humans; Kaplan-Meier Estimate; Leucovorin; Middle Aged; Neoplasm Staging; Neutropenia; Organoplatinum Compounds; Retrospective Studies; Thrombocytopenia; Treatment Outcome

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

Transcatheter arterial embolization (TAE) with gelatin sponge particles and iodized oil often yields poor results when used to treat unresectable multifocal hepatocellular carcinoma (HCC). The present study retrospectively investigated the utility of a novel combination chemotherapy regimen for treating multifocal HCC resistant to TAE.. Thirteen consecutive patients with unresectable multifocal HCC and resistance to TAE were treated with combination chemotherapy consisting of arterial chemoembolization with degradable starch microspheres (DSM) (150-4500 mg on Day 1), mitomycin-C (4-8 mg on Day 1), continuous arterial infusion of 5-fluorouracil (1250 mg/120 h), cisplatin (25-50 mg/120 h) and l-leucovorin (125 mg/120 h) for 10-19 weeks.. The response rate was 84.6%, with complete response in one patient and partial response (PR) in 10 patients. In four of 10 patients with PR, the tumor was not observable, although the tumor marker did not completely decline to the normal range. The 1-, 2- and 3-year survival rates were 100, 28.9 and 9.6% in all, and 100, 33.3 and 0% in six patients with portal vein tumor thrombosis (PVTT). The median survival was 22.1 months in all and 17.1 months in six patients with PVTT. Thrombocytopenia of Grade III or higher was observed in eight patients. Laparoscopic splenectomy was performed before therapy in four patients with platelet counts of <70,000/mm(3), and during therapy in five patients with severe thrombocytopenia.. This novel chemotherapy regimen achieved favorable results and may be useful in treating patients with unresectable multifocal HCC resistant to TAE.

Topics: Absorbable Implants; Aged; alpha-Fetoproteins; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Cisplatin; Combined Modality Therapy; Fluorouracil; Humans; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Male; Microspheres; Middle Aged; Mitomycin; Neoplasms, Multiple Primary; Retrospective Studies; Splenectomy; Starch; Survival Analysis; Thrombocytopenia

Oxaliplatin is a third generation platinum compound used in patients with advanced colorectal carcinoma. Recently, the mechanism of a rare drug-induced immune thrombocytopenia in patients receiving oxaliplatin has been described. This complication is caused by oxaliplatin-dependent antibodies directed against platelet surface glycoproteins, and is unrelated to myelosuppression. In this report, we describe two patients who developed thrombocytopenia immediately soon after receiving oxaliplatin. Sensitization presumably had occurred after receiving oxaliplatin during preceding courses of multiagent chemotherapy that included oxaliplatin.

Topics: Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Blood Platelets; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Membrane Glycoproteins; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Thrombocytopenia

Oxaliplatin (L-OHP) was administered to 10 patients previously treated for refractory advanced or recurrent colorectal cancer. The number of times each had received previous chemotherapy treatment ranged from 1 to 5 (median 3) for durations of 2.5 to 52.8 (median 11.7) months. At the time, L-OHP was not yet approved for sale in Japan, and could only be imported from overseas for personal use. As this made it very expensive,we used a low L-OHP dose of 100 mg/body. Combinations with 5-FU were administered differently from previous regimens; these included chronotherapy, weekly high-dose, FOLFOX 4, and FOLFOX 6. L-OHP was administered from 1 to 14 times (median 4.5), and the response to treatment was PR in 2 patients and NC in 5. The response rate was 22.2%. Although in NC there was a tendency toward tumor reduction in 2 of the 5 patients, the treatment had to be suspended because of their financial situations. Overall survival from commencement of the first treatment was 3.1 to 58.7 months (median 17.6+) and after starting L-OHP was 0.6 to 17.2 months (median 6.4+). Adverse events included bone marrow suppression in three patients, 3 cases of leukocytopenia (grade 3 in two patients and grade 4 in one), grade 4 thrombocytopenia in one patient,grade 3 sensory disturbance in one patient,and grade 3 anorexia in two patients. All reactions were able to be controlled except for one patient with Grade 4 thrombocytopenia. In summary,treatment with L-OHP as salvage chemotherapy can possibly contribute to prolongation of survival time in cases of refractory advanced colorectal cancer. It is useful to combine L-OHP with high-dose continuous administration of 5-FU,namely FOLFOX regimens.FOLFOX 6 is the most useful of the FOLFOX regimens because it is simple and can be administered on an outpatient basis.

Topics: Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Liver Neoplasms; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Salvage Therapy; Thrombocytopenia

We describe an unusual case of hepatosplenic T-cell lymphoma in a 61-year-old man who presented with fever, hepatosplenomegaly, anemia, and thrombocytopenia. A spleen biopsy was consistent with T-cell lymphoma. Cytogenetic studies did not reveal chromosome abnormalities. Using the polymerase chain reaction approach, clonality of the T-cell receptor gamma-chain gene rearrangement could be demonstrated, while Southern blot analysis disclosed only a germline configuration of the T-cell receptor beta chain genes. Of interest, an immune-mediated mechanism was demonstrated and was most likely responsible for erythrocyte and platelet destruction; this is, therefore, the first report of gamma T-cell lymphoma in association with Evans' syndrome. Initial steroid treatment was efficacious in limiting autoimmunity but constitutional symptoms did not subside. Chemotherapy (MACOP-B) was successful in obtaining complete clinical remission. Finally, thrombocytopenia in gammadelta T-cell lymphoma patients should be routinely evaluated for platelet autoantibodies.

Topics: Anemia, Hemolytic; Antineoplastic Combined Chemotherapy Protocols; Autoantibodies; Autoimmune Diseases; Biopsy; Bleomycin; Blood Platelets; Bone Marrow; Cyclophosphamide; Doxorubicin; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; Hepatomegaly; Humans; Hydrocortisone; Leucovorin; Liver Neoplasms; Lymphoma, T-Cell; Male; Methotrexate; Middle Aged; Prednisone; Receptors, Antigen, T-Cell, gamma-delta; Remission Induction; Splenic Neoplasms; Splenomegaly; Syndrome; Thrombocytopenia; Vincristine

The best chemotherapeutic regimen for advanced carcinoma of the esophagus remains to be determined. We have evaluated a combination of carboplatin, cisplatin and 5FU modulated by folinic acid. Patients. Twenty-seven patients (median age 57 yrs) with an unresectable carcinoma of the esophagus were included in this trial: 9 patients with a local relapse after surgery, 6 patients with a locally advanced (T4) tumor, and 12 patients with metastasis. Treatment schedule. Initial chemotherapy : carboplatine IV d1, AUC4; 5FU: bolus injection of 400 mg/m2 d1, followed by a continuous infusion of 600 mg/m2/24 h, d1 and d2; folinic acid (200 mg/m2) IV, before the 5FU bolus, d1 and d2; cisplatine 80 mg/m2, d3; on d15 and d16, 5FU and folinic acid were repeated with the same schedule. The second cycle began on d28. Concomitant chemo-radiotherapy with 5FU (1,000 mg/m2 d1 to d3), cisplatine (50 mg/m2 d1 and d2) and external irradiation (20 Gy in 10 fractions from d1 to d12) was then performed, for three cycles (until a total dose of 60 Gy). Results.. neutropenia grade 3-4 (32%), thrombopenia grade 3-4 (18%). More important, a lymphopenia (< 500/mm3) was noted in 12 patients (43%). Accordingly, 4 serious infectious complications were observed, with three toxic deaths. Objective response rate: 44% after initial chemotherapy; 75% after chemoradiotherapy, with 8 complete responses (38%). Median survival was 7.4 months, with a one- and two-year survival of 33% and 17,8%, respectively. Conclusion. This association of cisplatin, carboplatin, and 5FU did not offer a better response rate than the classical 5FU-cisplatinum association. But serious infectious complications occurred during the trial. We do not recommended further evaluation of this biplatinum therapy with 5FU in advanced esophageal carcinomas.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cisplatin; Combined Modality Therapy; Esophageal Neoplasms; Female; Fluorouracil; Humans; Kidney; Leucovorin; Lymphopenia; Male; Middle Aged; Neutropenia; Prospective Studies; Survival Analysis; Thrombocytopenia

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Colonic Neoplasms; Fluorouracil; Hemolysis; Humans; Immunoglobulin G; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Thrombocytopenia

Raltitrexed (RTX) is an antifolate thymidylate synthase (TS) inhibitor that is effective for the treatment of advanced colorectal cancer and other solid tumors. However, a small minority of patients receiving RTX monotherapy will experience grade III/IV gastrointestinal toxicity that can be life-threatening, particularly if copresenting with neutropenia. Lack of vigilance in recognition and treatment of symptoms of toxicity or violations of protocol have led to treatment-related deaths in some hospitals. The safety of RTX could be improved if an effective rescue agent was available. Leucovorin (LV) is a reduced folate cofactor that competes with RTX for transport and polyglutamation in both tumor and normal tissues and thus has potential as a rescue agent. In vitro cell studies are presented suggesting that the growth-inhibitory, and potentially cytotoxic, effects of RTX on populations of viable cells can be reversed by the delayed administration of LV. The mechanisms involved are inhibition of further drug uptake and polyglutamation and a redistribution and/or reduction in the concentration of preformed raltitrexed polyglutamates. A more clinically relevant in vivo mouse model was used to test the hypothesis further. BALB/c mice treated with 100 mg/kg/day x 4 days of RTX were used as a model for gastrointestinal and bone marrow toxicity. LV (200 mg/kg), which was given after the onset of severe weight loss and diarrhea (twice daily, days 5-7), prevented further weight loss and induced earlier recovery. This was accompanied by improvement in the histological appearance of the intestine (day 7) and the concentration of neutrophils and platelets in the blood (day 9). BALB/c mice could not tolerate 100 mg/kg daily x 5 days unless LV (200 mg/kg twice daily) was given on days 6-8. Measurement of RTX (polyglutamates) by RIA after 100 mg/kg RTX daily (days 1-4) showed less drug in plasma (3-4-fold), liver (8-11-fold), kidney (3-4-fold), and small intestinal epithelium (3-4-fold) on day 7 in LV-treated mice (100 or 200 mg/kg twice daily) compared with controls. A single injection of 100 mg/kg RTX (day 1) gave plasma levels of 3-4 pmol/ml on day 4 that are more clinically relevant. Administration of LV (100 or 200 mg/kg; twice daily on days 4-6) reduced the RTX concentration in the liver 2-4-fold on days 7, 9, and 11 compared with controls. A model is proposed where LV and/or its anabolic products can compete with RTX uptake into tissues and interfere with the hom

Topics: Animals; Antimetabolites, Antineoplastic; Body Weight; Cell Division; Cell Line; Drug Interactions; Humans; Intestinal Mucosa; Intestine, Small; Leucovorin; Leukemia L1210; Lymphocytes; Male; Mice; Mice, Inbred BALB C; Neutropenia; Polyglutamic Acid; Quinazolines; Thiophenes; Thrombocytopenia

Microangiopathic hemolytic anemia (MAHA) and disseminated intravasal coagulation (DIC) as initial paraneoplastic symptoms of a solid tumor present a rare clinical situation.. In 1998 a female patient was admitted due to multiple thrombosis, thrombocytopenia and fever. The initial diagnostic procedures revealed peri-aortic lymphomas and a tumor bulk (7 x 8 cm) in the upper abdomen. Gastroscopy revealed a 2 cm ulcer at the back side of the gastric corpus. Histologically, a signet-ring cell carcinoma was diagnosed. Final diagnosis stated a multilocular metastasising gastric cancer with infiltration of bone, peritoneum and dura and signet-cell infiltration of the bone marrow. Hematologic investigation in view of multiple paraneoplastic thrombosis revealed a microangiopathic hemolytic anemia associated with disseminated intravasal coagulation. Parallel to initial symptomatic therapy of coagulopathy, systemic cytostatic therapy with CDDP and VP-16 was initiated. In addition, radiotherapy of the brain was performed. After histologic confirmation of the diagnosis, weekly therapy with 5-FU (2600 mg/m2) and folinic acid (500 mg/m2) according to the Ardalan protocol was performed. After first signs of moderate response, oxaliplatin (60 mg/m2, day 1) was added. Although the chemotherapy dose had to be reduced due to prolonged neutropenia, the disturbances of hemostasis resolved completely resulting in reduced substitution rates with fresh frozen plasma (FFP) and platelets. Unfortunately, the patient died at home due to pulmonary embolism.. Tumor-associated hemostaseologic alteration requires immediate substitution of FFP and platelets. However, it should be followed by specific therapy of malignancy, since tumor-induced metabolites (e.g. mucin) maintain the alteration of hemostasis. Chemotherapy may therefore be the best strategy to prevent complications such as MAHA and DIC.

Topics: Algorithms; Anemia, Hemolytic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Marrow Neoplasms; Carcinoma, Signet Ring Cell; Cisplatin; Diagnosis, Differential; Disseminated Intravascular Coagulation; Etoposide; Female; Fluorouracil; Hemorrhagic Disorders; Humans; Leucovorin; Middle Aged; Neoplasm Metastasis; Precancerous Conditions; Stomach; Stomach Neoplasms; Thrombocytopenia

Hemodialysis, hemoperfusion, thymidine, and carboxypeptidase have been recommended together with high-dose (HD) leucovorin (LV) to treat patients at risk for methotrexate (MTX) toxicity. To elucidate the efficacy of high LV rescue as the sole salvage modality for severe MTX intoxication, we studied 13 patients who were treated in this fashion at Memorial Sloan-Kettering Cancer Center (New York, NY).. To identify patients at high risk for severe MTX toxicity, we performed a retrospective review of all patients with MTX levels greater than 100 micromol/L at 24 hours and greater than 10 micromol/L at 48 hours after HD MTX.. A total of 13 patients were identified. The median MTX concentration was 164 micromol/L at 24 hours (range, 102 to 940 micromol/L), 16.3 micromol/L at 48 hours (range, 10.5 to 190 micromol/L), and 6.2 micromol/L at 72 hours (range, 1.35 to 39 micromol/L). MTX levels remained greater than 0.1 micromol/L for an average of 11 +/- 3 days (mean +/- SD) (range, 7 to 17 days). In addition to supportive treatment with hydration and sodium bicarbonate administration, all patients were treated solely with HD LV, which was started within the first 24 hours in nine patients, 48 hours in three patients, and 72 hours in one patient in doses that varied from 0.24 to 8 g/d. Significant neutropenia (neutrophil count < 1,000/ microL) occurred in eight patients and lasted for 1 to 5 days. Thrombocytopenia (platelet count < 100,000/microL) occurred in seven patients and lasted for 5 to 10 days. Other toxic manifestations included mucositis of varying degrees, diarrhea, and neutropenic fever, but all patients recovered.. In the range of MTX levels observed, HD LV can be used as a sole therapy for MTX toxicity without the need for extracorporeal removal and with tolerable morbidity.

Topics: Antidotes; Antimetabolites, Antineoplastic; Bone Neoplasms; Child; Creatinine; Drug Administration Schedule; Female; Folic Acid Antagonists; Humans; Kidney; Leucovorin; Methotrexate; Neutropenia; Osteosarcoma; Retrospective Studies; Thrombocytopenia

Acute disseminated intravascular coagulation (DIC) is a severe complication of gastric adenocarcinoma, and most of the patients die within 1-3 weeks. We have treated five such patients with an empirical non-myelosuppressive HDFL regimen (weekly 24h infusion of high-dose 5-fluorouracil 2600 mg/m2 and leucovorin 300 mg/m2). Within 2 weeks of starting the treatment the clinical and laboratory evidence of acute DIC quickly resolved in all five patients. HDFL not only caused no further myelosuppression, but also resulted in normalization of the patient's haemogram within a few weeks. Other anti-cancer drugs could then be safely added. Three patients had a survival time of more than 6 months. We suggest that HDFL is an ideal initial treatment for gastric cancer complicated by acute DIC.

Topics: Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Disease-Free Survival; Disseminated Intravascular Coagulation; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Stomach Neoplasms; Survival Analysis; Thrombocytopenia; Treatment Outcome

Irinotecan is currently used as second-line chemotherapy for advanced colorectal cancer. We report a case of severe thrombocytopenia after Irinotecan, suggesting an immune mechanism, in a 53-year-old patient.. The patient's sera were screened for platelet antibodies with an indirect platelet immunofluorescence test (PIIFT). The monoclonal antibody immobilization of platelet antigen assay (MAIPA) was used to characterize the antibody target.. We detected an IgG platelet antibody in the patient's serum in the presence of Irinotecan by means of PIIFT, and not in the presence of SN-38, its active metabolite. The specificity of the binding was asserted after CD32 MoAb blockade. The platelet binding site could not be strictly identified with MAIPA and immunoblotting but GpIIb/IIIa can be excluded after experiments with Glanzmann platelets.. This case can be considered the first documented Irinotecan-induced immune thrombocytopenia.

Topics: Adenocarcinoma; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Blood Platelets; Camptothecin; Colonic Neoplasms; Fluorouracil; Humans; Immunoglobulin G; Irinotecan; Leucovorin; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Thrombocytopenia

Epidural hematoma is a rare cause of spinal cord compression, which usually provokes severe neurological deficits. It is presumed to originate from venous or, more probably, arterial bleeding. Thrombocytopenia and other disorders of coagulation may precipitate the onset of epidural hematoma and facilitate the evolution of the disease. We report the case of a patient suffering from a non-Hodgkin's lymphoma with severe thrombocytopenia during a MACOP-B schedule, who presented with a spontaneous cervical epidural hematoma. We discuss the etiopathological aspects, diagnosis, and treatment of this rare cause of acute cervical spinal cord compression.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Hematoma, Epidural, Cranial; Humans; Leucovorin; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Prednisone; Spinal Cord Compression; Thrombocytopenia; Vincristine

This study utilized a recently developed culture and quantitation system to detect megakaryocyte precursors in CD34+ bone marrow cells from normal donors and breast cancer patients treated with 5-fluorouracil, leucovorin, adriamycin and cyclophosphamide (FLAC). Bone marrow was obtained from patients before and then after their first cycle of FLAC once blood cell counts had recovered. CD34+ cells were isolated and placed in liquid culture with growth factors to stimulate proliferation and lineage commitment. Absorbance values from an enzyme-linked immunosorbent assay were used to quantitate expression of platelet glycoprotein GPIIb/IIIa. There was an increase in absorbance with increasing numbers of cells seeded per culture that was associated with an increase in the number of megakaryocyte lineage cells produced. After 10 days in liquid culture, absorbance values for expression of GPIIb/IIIa from 2,000 normal donor and pre-chemotherapy CD34+ marrow cells were > or = 1.0. Absorbance values from cultures of post-chemotherapy CD34+ cells from four patients were similar to values from pre-chemotherapy CD34+ cells. In contrast, absorbance values from cultures of post-chemotherapy CD34+ cells from two other patients were low (absorbance < 0.5). Low absorbance values for GPIIb/IIIa expression indicate that megakaryocyte production from those CD34+ cells was reduced. Both of those patients developed prolonged thrombocytopenia and platelet nadirs of less than 20,000/microl during FLAC chemotherapy. In contrast, only one out of four patients whose cultures of post-chemotherapy CD34+ cells had absorbance values > or = 1.0 developed platelet nadirs less than 20,000/microl. These results suggest that low platelet nadirs and delayed platelet recovery may be associated with suppressive effects of chemotherapy on recovery of megakaryocyte precursors.

Topics: Antigens, CD34; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Blood Cell Count; Blood Platelets; Bone Marrow Cells; Breast Neoplasms; Case-Control Studies; Cyclophosphamide; Doxorubicin; Enzyme-Linked Immunosorbent Assay; Female; Fluorouracil; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interleukin-3; Leucovorin; Megakaryocytes; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Fusion Proteins; Stem Cell Factor; Thrombocytopenia; Time Factors

The authors evaluated a high-intensity inpatient regimen using augmented but subtransplantation doses of multiple agents in patients with metastatic breast cancer. Two high-dose courses were given in an attempt to improve the efficacy of high-dose regimens using a single course.. Forty women received treatment between October 1988 and October 1991. The median age was 38 years (range, 24-56 years). Twenty-five patients were receiving their first chemotherapy for metastatic disease; 15 patients had received one or more prior regimens. The patients received two courses of chemotherapy, which consisted of the following: cyclophosphamide 1500 mg/m2 intravenously (i.v.) on days 1 and 2; doxorubicin 45 mg/m2 i.v. on days 1 and 2; cisplatin 20 mg/m2 i.v. on days 1, 2, 3, 8, 9, and 10; 5-fluorouracil 1000 mg/m2 on days 8, 9, and 10 (continuous infusion); methotrexate 100 mg/m2 i.v. on days 15 and 22; leucovorin 15 mg/m2 i.v. or by mouth for four doses beginning 24 hours after methotrexate. Etoposide 400 mg/m2 i.v. on days 1, 2, and 3 was substituted for doxorubicin in 14 patients who had received prior doxorubicin.. Twenty-nine of 40 patients (73%) had objective response to therapy, with 10 (25%) complete responses. Four patients who obtained a complete response remain disease-free at 14, 21, 28, and 32 months, respectively; all of these patients received this regimen as first-line therapy for metastatic disease. Myelosuppression was severe, with median durations of leukocytes less than 1000/microliters and platelets less than 50,000/microliters of 15 days (range, 7-48 days) and 13 days (range, 3-49 days), respectively. Moderate or severe mucositis occurred in 56 of 68 courses. Four patients (10%) had treatment-related deaths.. This regimen produced high overall response and complete response rates compared with standard regimens. However, only 15% of patients who received this therapy as first-line treatment for metastatic breast cancer remain disease-free, and median response duration was shorter than that reported using high-dose therapy with bone marrow support. Toxicity with this regimen was greater than anticipated, although myelosuppression and stomatitis would be reduced by the use of cytokines. This regimen does not improve results achieved with standard therapy sufficiently to justify its toxicity and expense.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Neoplasms; Brain Neoplasms; Breast Neoplasms; Cisplatin; Cyclophosphamide; Doxorubicin; Etoposide; Female; Fluorouracil; Follow-Up Studies; Hemorrhage; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Methotrexate; Middle Aged; Neutropenia; Remission Induction; Survival Rate; Thrombocytopenia

Seventy-eight individuals previously treated with chemotherapy for non-Hodgkin's lymphoma were enrolled in a phase II pilot study employing methotrexate 100 mg/M2 iv (day 1), calcium leucovorin 10 mg/M2 iv and/or po q6h (days 2-4), VM-26 (teniposide) 100 mg/M2 iv (days 2 and 9), procarbazine 100 mg/M2 po (days 2-15), and dexamethasone 15 mg/M2po (days 2-8) (MV26PD). Thirty percent of the 78 patients treated had a response to therapy (8% complete, 22% partial). Twenty-four percent of patients with diffuse histiocytic (large cell) lymphoma had a response (12% complete, 12% partial). The estimated failure-free survival was 41% at 3 months and the median survival (death from any cause) was 4.5 months for the entire cohort. Two individuals, including one individual with diffuse histiocytic lymphoma, remain in a complete response for over 900 days. Significant hematologic toxicity and infectious complications were seen in this heavily pretreated group of patients. MV26PD represents an active combination of agents for the treatment of non-Hodgkin's lymphoma. The optimal dosing for MV26PD remains to be determined.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Dexamethasone; Drug Evaluation; Female; Humans; Leucovorin; Leukopenia; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Neutropenia; Procarbazine; Teniposide; Thrombocytopenia; Vincristine

12 AIDS/ARC patients with or suspected of Pneumocystis carinii pneumonia were treated with co-trimoxazole and received supplementary folic or folinic acid to avoid peripheral blood cytopenia. Most patients developed decreased numbers of neutrophils and hemoglobin while receiving co-trimoxazole. Supplementary folate/folinate could not abolish the drug-induced cytopenia. Routine prescription of folinic acid is not recommended. Folic acid is cheap and may be beneficial and should be prescribed.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Anemia; Drug Combinations; Folic Acid; Hematologic Diseases; Humans; Leucovorin; Leukopenia; Pneumonia, Pneumocystis; Prospective Studies; Sulfamethoxazole; Thrombocytopenia; Time Factors; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Treatment results remain very poor for some clinical and histopathologic subsets of patients with aggressive non-Hodgkin's lymphoma. We treated 21 such patients with a high-dose combination chemotherapy regimen [Mega-COMLA (cyclophosphamide, cytarabine, vincristine, and methotrexate followed by leucovorin and prednisone) + CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)] in an attempt to improve disease-free survival. Neoplasms were classified using the Lukes-Collins system. Eight patients had T-cell lymphomas (convoluted lymphocytic lymphoma, four patients; T-cell lymphoma/leukemia, one; and peripheral T-cell lymphoma, three), eight had B-cell lymphomas (immunoblastic sarcoma, five patients; small noncleaved follicular center cell, one; and large noncleaved follicular center cell, two), and five had nontypable large noncleaved cell lymphomas. All patients were previously untreated; 18 of 21 patients had clinical stage III or IV disease. Following induction therapy (4-8 weeks' duration), 16 patients (76%) achieved complete remission, while three had partial remission. Two patients died of sepsis during induction therapy. Eleven of 16 complete responders (69%) remain in complete remission after a median follow-up of 35 months. The actuarial 3-year survival rate is 51% for the entire group. Myelosuppression with this regimen was severe and prolonged, with a median duration of neutropenia (less than 500 cells/microliter) of 14 days. Seven patients (33%) developed severe neuropathy following induction treatment. High-dose induction therapy with this regimen resulted in a high complete remission rate with manageable toxicity. Survival results are encouraging when compared retrospectively to our patients with similar poor-prognosis histologies treated with standard combination chemotherapy. However, the value of this intensive therapy, relative to newer ("third-generation") regimens, can only be established by prospective randomized studies.

Topics: Actuarial Analysis; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Administration Schedule; Female; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Neoplasm Staging; Neutropenia; Peripheral Nervous System Diseases; Prednisone; Prognosis; Thrombocytopenia; Vincristine

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

Twenty-three patients with metastatic breast carcinoma were induced with a complex systemic therapy regimen in an attempt to ascertain if a complete remission rate greater than 50% could be obtained with intensive drug exposure. The durability of the remissions was observed by discontinuing therapy after 3 cycles in complete remission or after 6 cycles of treatment, whichever was longer. In 13 patients consolidation radiation therapy to the pre-treatment sites of disease was administered after discontinuing systemic therapy. Each 28 day cycle of the drug regimen consisted of pulses of adriamycin, vincristine, dibromodulcitol, prednisone, methotrexate with leukovorin rescue, hexamethylmelamine, bleomycin (discontinued after entry #17), fluoxymesterone, and tamoxifen. Eighteen of the 23 patients achieved complete remissions (78%) and 3 had partial remissions. The median times to treatment failure and survival were, respectively, 12.3 and 19.4 mos. The times for complete remission patients were, respectively, 13.5 and 23.9 mos. Consolidation radiotherapy at greater than or equal to 40 Gy to drug induced pre-study sites of complete remission was associated with first relapses at pre-study sites in 5/30 (17%) instances, compared to 21/35 (60%) in sites not receiving radiotherapy. Side-effects were commensurate with the intensity of the treatment program and are detailed in the text. Although the achievement of a high complete remission rate is promising, the failure to extend their duration beyond that of historical data suggests that additional conceptual and therapeutic approaches need to be explored.

Topics: Altretamine; Antineoplastic Agents; Bleomycin; Breast Neoplasms; Combined Modality Therapy; Doxorubicin; Drug Administration Schedule; Female; Fluoxymesterone; Humans; Leucovorin; Leukopenia; Lung; Methotrexate; Mitolactol; Neoplasm Metastasis; Prednisone; Receptors, Estrogen; Tamoxifen; Thrombocytopenia; Time Factors; Vincristine

Modified triple chemotherapy (MAC III: methotrexate with citrovorum factor, actinomycin D, and cyclophosphamide) was administered as primary treatment to 14 patients with high-risk metastatic gestational trophoblastic tumors (GTT). Ten (71.4%) patients attained complete remission with 1 to 4 courses of MAC III (mean = 2.7 courses). Three of the remaining patients subsequently achieved remission with the modified Bagshawe regimen or vinblastine, bleomycin, and cis-platinum. Following 38 courses of MAC III, moderate hepatotoxicity (SGOT greater than or equal to 150 U) developed after 1 (2.6%) course. Marked thrombocytopenia (platelets less than 50,000/mm3) and marked granulocytopenia (granulocytes less than 500/mm3) developed after 7 (18.4%) and 19 (50%) of the courses, respectively. Platelet transfusions were administered after 4 (10.5%) courses of MAC III and no patient required granulocyte transfusions. MAC III is an effective alternative treatment for patients with high-risk metastatic GTT.

Topics: Adolescent; Adult; Agranulocytosis; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Chemical and Drug Induced Liver Injury; Chorionic Gonadotropin; Cisplatin; Cyclophosphamide; Dactinomycin; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Leucovorin; Methotrexate; Middle Aged; Neoplasm Metastasis; Pregnancy; Pregnancy Complications, Neoplastic; Risk; Thrombocytopenia; Trophoblastic Neoplasms; Uterine Neoplasms; Vinblastine

Few studies have incorporated high-dose methotrexate (MTX) with leucovorin rescue in the treatment of small cell lung cancer (SCLC). Potentially therapeutic levels of MTX can be achieved in the central nervous system (CNS) by systemic administration of high doses of this drug. Utilizing a combination chemotherapy program of Adriamycin, vincristine, cyclophosphamide, and methotrexate, 31 patients were sequentially assigned to receive either low-dose MTX (40 mg/m2), or high-dose MTX (500 mg/m2) with leucovorin rescue. Radiation therapy to the primary site was also administered. At these dosage levels there were no statistically significant differences in response rate or survival between the two groups. High-dose MTX did not prevent the appearance of CNS disease; there being 2/15 and 3/15 CNS relapses in the HD MTX and LD MTX treated groups, respectively. The occurrence of CNS disease did not significantly affect overall survival as compared to patients not similarly affected.

Topics: Aged; Carcinoma, Small Cell; Drug Therapy, Combination; Female; Humans; Leucovorin; Leukopenia; Lung Neoplasms; Male; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Nervous System Neoplasms; Paraneoplastic Syndromes; Smoking; Thrombocytopenia

Methotrexate with citrovorum rescue (MTX-CF) was administered as primary treatment in 106 patients with gestational trophoblastic disease (GTD). Ninety-six patients (90.6%) achieved complete remission with MTX-CF and 77 of these patients (80.2%) required only one course of MTX-CF to attain remission. MTX-CF induced sustained remission in 89 (94.7%) of 94 patients with nonmetastatic GTD and in seven (59.3%) of 12 patients with low-risk metastatic GTD. Resistance to MTX-CF was more common in patients with disseminated disease and with pretreatment hCG titers greater than or equal to 50,000 milliIU/ml. Following MTX-CF, granulocytopenia, thrombocytopenia and hepatotoxicity was observed in only seven (6.6%), three (2.8%), and ten (9.4%) patients, respectively. MTX-CF should be the preferred primary treatment in nonmetastatic and low-risk metastatic GTD.

Topics: Adolescent; Adult; Agranulocytosis; Chemical and Drug Induced Liver Injury; Dactinomycin; Drug Therapy, Combination; Female; Humans; Leucovorin; Methotrexate; Middle Aged; Neoplasm Metastasis; Pregnancy; Thrombocytopenia; Trophoblastic Neoplasms; Uterine Neoplasms

Topics: Adult; Female; Humans; Leucovorin; Leukopenia; Pyrimethamine; Thrombocytopenia; Toxoplasmosis, Ocular

Topics: Antineoplastic Agents; Cyclophosphamide; Cytarabine; Doxorubicin; Humans; Leucovorin; Leukopenia; Lymphoma, Large B-Cell, Diffuse; Methotrexate; Prednisone; Procarbazine; Radiotherapy, High-Energy; Thrombocytopenia; Vincristine

The occurrence of overall toxicity was analyzed for 43 patients with osteosarcoma who received 349 high-dosage courses of methotrexate (HD-MTX) with citrovorum factor (Leukovorin) "rescue" (CF). The dosages of HD-MTX ranged from 50 to 350 mg/kg. Overall toxicity was assessed on the basis of five manifestations of toxicity: stomatitis, dermatitis, myelosuppression, liver dysfunction, and kidney function abnormalities. The great majority (91.4%) of the infusions were well tolerated, but 8.6% were associated with moderate or severe toxicity. Stomatitis and serum glutamic-oxaloacetic transaminase (SGOT) changes were the most frequent postinfusion findings. Three patients died from causes related to MTX toxicity. Dose, age, sex, and number of prior infusions were investigated by logistic regression analysis for prognostic effect on frequency of moderate to severe overall toxicity. Age and number of prior infusions had significant (P less than 0.06) effects on overall toxicity. Patients older than 15 years with greater than 10 prior infusions constituted the "high risk" group with a risk of moderate to severe toxicity 6.3 times that of the younger patients with fewer than 10 infusions.

Topics: Adolescent; Age Factors; Bone Marrow; Bone Neoplasms; Child; Dermatitis; Drug Administration Schedule; Female; Humans; Kidney; Leucovorin; Leukopenia; Liver; Male; Methotrexate; Osteosarcoma; Sex Factors; Stomatitis; Thrombocytopenia; Vincristine

Topics: Bone Marrow; Bone Marrow Diseases; Humans; Leucovorin; Leukopenia; Pyrimidines; Thrombocytopenia

Topics: Blood Cell Count; Blood Platelets; Female; Humans; Leucovorin; Methotrexate; Pregnancy; Thrombocytopenia; Thrombocytosis; Time Factors; Trophoblastic Neoplasms; Uterine Neoplasms

Topics: Adult; Bone Marrow; Bone Marrow Diseases; Female; Humans; Leucovorin; Pregnancy; Pregnancy Complications, Infectious; Pyrimethamine; Thrombocytopenia; Time Factors; Toxoplasmosis; Toxoplasmosis, Congenital

Topics: Agranulocytosis; Antineoplastic Agents; Breast Neoplasms; Female; Hemangiosarcoma; Hodgkin Disease; Humans; Kidney Neoplasms; Leucovorin; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Lung Neoplasms; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Melanoma; Methotrexate; Osteosarcoma; Pancreatic Neoplasms; Radiography; Rectal Neoplasms; Rhabdomyosarcoma; Testicular Neoplasms; Thrombocytopenia

Topics: Adenocarcinoma, Mucinous; Adult; Aged; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Infusions, Parenteral; Jaw Neoplasms; Laryngeal Neoplasms; Leucovorin; Leukopenia; Male; Methotrexate; Middle Aged; Mouth Neoplasms; Neoplasm Metastasis; Neoplasms; Paranasal Sinus Neoplasms; Pharyngeal Neoplasms; Salivary Glands; Thrombocytopenia; Tongue Neoplasms; Tonsillar Neoplasms

Topics: Adult; Anemia, Macrocytic; Female; Folic Acid; Folic Acid Deficiency; Hemorrhagic Disorders; Humans; Leucovorin; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications, Hematologic; Thrombocytopenia

Topics: Anemia; Anemia, Macrocytic; Blood Platelets; Drug Therapy; Folic Acid; Hemoglobinometry; Humans; Leucovorin; Leukocyte Count; Metabolism; Myocarditis; Pigmentation Disorders; Purpura; Purpura, Thrombocytopenic; Pyrimethamine; Sulfonamides; Thrombocytopenia; Toxicology; Toxoplasmosis; Toxoplasmosis, Ocular