levoleucovorin and Agranulocytosis

Topics: Agranulocytosis; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Diarrhea; Drug Resistance, Neoplasm; Fluorouracil; Humans; Irinotecan; Leucovorin; Neoplasm Staging; Survival Analysis

To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and irinotecan (S-1/irinotecan) therapy.. The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan. The median follow-up was 60 months.. Grade 3 adverse effects occurred in 7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%) were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a pathological complete response (ypCR). At 60 months, the local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the only independent prognostic factor for DFS (P=.0019) and OS (P=.0064) in the study group as a whole. Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both ypT (P=.0065) and tumor location (P=.003) were independent predictors of DFS. A combination of these factors was very strongly related to high risk of recurrence (P<.0001), which occurred most commonly in the lung.. NCRT with concurrent S-1/irinotecan produced high response rates and excellent long-term survival, with acceptable adverse effects in patients with rectal cancer. ypN2 is a strong predictor of dismal outcomes, and a combination of ypT and tumor location can identify high-risk patients among those with ypN0/1 disease.

Topics: Adult; Aged; Aged, 80 and over; Agranulocytosis; Analysis of Variance; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemoradiotherapy; Diarrhea; Disease-Free Survival; Dose Fractionation, Radiation; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Leukopenia; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxonic Acid; Rectal Neoplasms; Tegafur; Treatment Outcome

In 1990, fluorouracil (FU) plus levamisole for 1 year became standard adjuvant treatment for patients with high-risk stages II and III colon cancer. Intergroup (INT) 0089 assessed the relative contributions of leucovorin and levamisole in such patients.. From 1988 to 1992, 3,794 patients were randomly assigned. Experimental treatment consisted of one of three chemotherapy regimens: the low-dose leucovorin plus FU (Mayo Clinic; LDLV) regimen, the high-dose leucovorin plus FU (Roswell Park; HDLV) regimen, and the low-dose leucovorin plus levamisole plus FU (LDLV plus LEV) regimen, each administered for 30 to 32 weeks. The control arm was levamisole plus FU (LEV) for 1 year.. After a median follow-up of 10 years, of 3,561 eligible patients, 1,691 (47%) have died and 1,330 (37%) have experienced disease recurrence; 137 (10%) of those experiencing recurrence are still alive. A total of 481 patients (13%) died without evidence of recurrence, and 1,723 (48%) are alive and disease free. Although there were toxicity differences among the four arms, none was statistically superior in disease-free or overall survival.. The 6- to 8-month regimens of LDLV and HDLV without levamisole used in this trial, rather than the previous standard regimen of 12 months of LEV, have become widely used. INT-0089 has long-term follow-up of the largest clinical trial of patients with high-risk colon cancer, documenting not only the durability of the treatment effects, but also the natural history of patients with high-risk colon cancer, and analyses of treatment based on age, race, and comorbid conditions such as obesity, diabetes, and second primary cancers.

Topics: Adenocarcinoma; Adjuvants, Immunologic; Adult; Aged; Agranulocytosis; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Diarrhea; Dose-Response Relationship, Drug; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Levamisole; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Patient Compliance; Risk Factors; Survival Analysis; Treatment Outcome; Vitamin B Complex

Thirty-two patients with nasal NK/T-cell lymphoma and disseminated disease (lung, skin, and bone marrow) were treated with an intensive combined therapy that consisted of three cycles of CMED (cyclophosphamide 2 g/m(2), metothrexate 200 mg/m(2), etoposide 600 mg/m(2), and dexamethasone 80 mg/m(2) with leucovorin rescue administered 24 h after) every 14 d, following high-dose radiotherapy: 55 Gy in 20 sesions to centrofacial region and three cycles more of the same chemotherapy regimen. To ameliorate the presence of severe granulocytopenia, granulocyte colony-stimulating factor, 5 microg/kg, daily for 14 d, begun on d 2 after chemotherapy, was administered. Complete response was achieved in 21 cases (65%); failure or progression was observed in 11 cases (35%). With a median follow-up of 69.1 mo, relapse has not been observed; thus, actuarial curves at 5 yr showed that event-free survival (EFS) is 100% in 21 patients and overall survival (OS) is 65%. Granulocytopenia grade IV was observed in 15% cycles, Nonhematological toxicity was mild and well tolerated. Radiotherapy was well tolerated; only mild mucositis was observed. Nasal NK/T-cell lymphoma is an rare presentation of malignant lymphoma (<1% of all cases) with a worse prognosis; less than 5% patients are alive free of disease at 1 yr. The use of intensive more specific chemotherapy and high dose of local radiotherapy, appear to be an excellent therapeutic approach with improvement in EFS and OS.

Topics: Adult; Aged; Agranulocytosis; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Neoplasms; Cyclophosphamide; Dexamethasone; Disease-Free Survival; Etoposide; Female; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Humans; Killer Cells, Natural; Leucovorin; Lung Neoplasms; Lymphoma, T-Cell; Male; Methotrexate; Middle Aged; Nose Neoplasms; Radiotherapy, Adjuvant; Remission Induction; Skin Neoplasms; Treatment Outcome

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

Chemotherapy has a limited impact on adenocarcinoma of the stomach. Although biochemical modulation of 5-fluorouracil (5-FU) by leucovorin (LV) and interferon-alpha (IFN-alpha) has improved the outcomes of patients with metastatic colorectal carcinoma compared with 5-FU alone, this approach has not been extensively evaluated in the treatment of advanced gastric carcinoma.. Twenty-seven patients with bidimensionally measurable, metastatic gastric carcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 received the combination of IFN-alpha (5 million U/m2 administered subcutaneously daily on Days 1-7), LV (500 mg/m2 administered intravenously over 30 minutes immediately after IFN-alpha on Days 2-6), and 5-FU (370 mg/m2 given as an intravenous bolus 60 minutes after LV on Days 2-6), with treatment repeated every 4 weeks. Oral cryotherapy was administered routinely before each dose of 5-FU to reduce the incidence of severe stomatitis.. The median age of the patients was 58 years (range, 20-76), and 22 patients had residual, unresectable primary lesions. The median number of cycles received was 3 (range, 1-11). Of 24 patients who received at least 2 cycles of treatment, 15 (62.5%) did not require dose reduction for toxicity during the initial 2 cycles. The predominant toxicities were gastrointestinal: diarrhea and stomatitis of Grade 3-4 occurred in 28.6% and 35.7% of patients, respectively. Other severe (Grade 3-4) toxicities were granulocytopenia (which occurred in 21.4% of patients) and fatigue (in 10.7%). Fever and flu-like symptoms were common but usually mild. Of 24 patients who were evaluable for response, 3 had partial responses (PR) of 16, 23, and 33 weeks' duration, respectively, for a response rate of 12.5% (95% confidence interval = 2.7-32.4%). Two additional patients had reductions in tumor size sufficient for PR, but scans to document the minimum required response duration of 4 weeks were not obtained before progressive disease occurred. The median progression-free and overall survivals were 2.5 and 7.8 months, respectively.. Although this regimen can be administered safely with appropriate supportive care to patients with good performance status, it has limited therapeutic activity in patients with advanced gastric carcinoma.

Topics: Adult; Aged; Agranulocytosis; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Interferon-alpha; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Stomach Neoplasms; Stomatitis; Treatment Outcome

To compare the efficacy and toxicity of fluorouracil (FU) and racemic leucovorin (d,l-LV) versus FU combined with the l-isomer of leucovorin (l-LV) in the treatment of advanced colorectal cancer.. A total of 248 patients with advanced measurable colorectal cancer previously unexposed to chemotherapy were randomly assigned to treatment with either FU (400 mg/m2/d by intravenous [I.V.] infusion for 2 hours) and racemic LV (100 mg/m2/d by I.V. bolus injection) given for 5 consecutive days, or the combination of FU and the pure l-isomer of LV using the same dose schedule. In both treatment arms, courses were administered every 28 days if toxicity allowed for a total of 6 months, unless evidence of tumor progression was documented earlier.. There were no significant differences between the FU/racemic LV and the FU/l-LV arm in the overall response rate (25% v 32%), duration of response (7.2 v 8.0 months), median time to progression or death (6.25 v 8.0 months), or median overall survival time (14.5 v 15.0 months). Except for minor myeloid toxic effects associated with FU/l-LV, there was also no significant difference in terms of adverse reactions. Gastrointestinal symptoms, specifically mucasitis and diarrhea, were less frequent and less severe in both treatment arms compared with other trials with FU/racemic LV reported in the literature, which might be because of the prolonged administration of FU used in both arms.. The combination of FU/l-LV produced response rates, response durations, and survival times similar to those with FU/d,l-LV. Biochemical modulation of FU by either pure l-LV or racemic LV thus appears to result in equivalent clinical efficacy.

Topics: Adult; Aged; Agranulocytosis; Antidotes; Antimetabolites, Antineoplastic; Colorectal Neoplasms; Disease Progression; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Neoplasm Staging; Stereoisomerism; Survival Analysis

The combination of radiation therapy with fluorouracil (5-FU)-based chemotherapy is generally accepted as appropriate postoperative therapy for patients with adenocarcinomas of the rectum that extend through the bowel wall or with lymph nodes positive for tumor. We attempted to determine whether the efficacy of this postoperative therapy could be improved by the addition of leucovorin and/or levamisole.. A total of 1,696 patients were randomized and eligible for treatment with one of four treatment schemes. All patients received two cycles of bolus 5-FU-based systemic chemotherapy followed by pelvic radiation therapy with chemotherapy and two more cycles of the same systemic chemotherapy. Chemotherapy was either 5-FU alone, 5-FU with leucovorin, 5-FU with levamisole, or 5-FU with leucovorin and levamisole.. With a median follow-up duration of 48 months, there is no statistically significant advantage to any of the treatment regimens compared with bolus 5-FU alone. There is evidence of increased gastrointestinal toxicity with the three-drug combination compared with bolus 5-FU alone. Statistical analysis suggests it is very unlikely that either levamisole-containing combination will be shown to be of value with further follow-up evaluation.. There is no evidence at present for a beneficial effect of levamisole in the adjuvant treatment of rectal cancer. Definitive evaluation of the effect of the addition of leucovorin to 5-FU and pelvic radiation will require further follow-up evaluation.

Topics: Adenocarcinoma; Adjuvants, Immunologic; Adult; Aged; Agranulocytosis; Antidotes; Antimetabolites, Antineoplastic; Cause of Death; Chemotherapy, Adjuvant; Combined Modality Therapy; Diarrhea; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Levamisole; Male; Middle Aged; Postoperative Period; Prospective Studies; Rectal Neoplasms; Survival Rate; Treatment Outcome

This prospective randomized trial was performed to compare the effectiveness of intravenous vinorelbine tartrate with intravenous fluorouracil and leucovorin (5-FU/LV) on the primary end points of survival, quality of life (QOL), and relief of cancer-related symptoms in patients with advanced non-small-cell lung cancer (NSCLC). Secondary end points included tumor response rates and time to treatment failure. In addition, the safety of both treatment regimens was evaluated in this multicenter study.. Two hundred sixteen patients with stage IV NSCLC were enrolled onto this study from 18 centers. Vinorelbine was administered at a dose of 30 mg/m2/wk. 5-FU/LV was administered at a dose of 425 mg/m2 and 20 mg/m2, respectively, for 5 consecutive days every 4 weeks. Patients with progressive disease or toxicity were removed from study while responding and stable patients were continued on therapy.. The median survival time of patients who received vinorelbine was 30 weeks, with 25% of patients alive at 1 year, compared with a median survival time of 22 weeks and 16% of patients alive at 1 year for those treated with 5-FU/LV (P = .03, log-rank test). This improvement in survival was associated with a higher objective response rate (12% v 3%) and time to treatment failure (10 weeks v 8 weeks) for vinorelbine versus 5-FU/LV. The dose-limiting toxicity of vinorelbine was granulocytopenia, with 54% of patients experiencing grade 3/4 granulocytopenia. Nonhematologic toxicity of vinorelbine was generally grade 1 or 2. The most common grade 3 toxicities were related to injection-site reactions.. This trial confirms the efficacy of vinorelbine in patients with advanced NSCLC. The clinical activity and relatively favorable toxicity profile of this agent make it a reasonable and useful treatment option in the management of patients with this disease.

Topics: Adult; Aged; Aged, 80 and over; Agranulocytosis; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Carcinoma, Non-Small-Cell Lung; Female; Fluorouracil; Humans; Injections, Intravenous; Leucovorin; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Prospective Studies; Quality of Life; Survival Analysis; Vinblastine; Vinorelbine

A variety of fluorinated pyrimidine-based regimens for the treatment of disseminated colorectal cancer have been presented in the medical literature. The Southwest Oncology Group designed a screening trial of seven regimens of fluorouracil (5-FU) to assess efficacy and toxicity afforded by biochemical modulation or schedule variations.. Six hundred twenty patients were entered into this trial between August 1989 and January 1993. Eligible patients were classified as having recurrent or disseminated disease that was measurable or nonmeasurable. All eligible patients were evaluated for toxicity and survival; patients with measurable disease were evaluated for response according to standard criteria.. No regimen achieved a higher response rate than single-agent bolus 5-FU. Eighty-four percent of patients have been monitored until death. The median survival time for the entire cohort is 14 months. Survival hazards ratios showed a positive trend in favor of the unmodulated infusion regimens, while high-grade toxicities occurred more frequently in the 5-FU bolus arms. The major high-grade toxicities were granulocytopenia and diarrhea.. In this trial, no regimen provided substantial improvement relative to 5-FU bolus or single-agent therapy for either response or survival in the treatment of disseminated colorectal cancer. The single-agent infusion regimens demonstrated the most encouraging results with a favorable toxicity profile and a 2-month longer survival duration than 5-FU bolus therapy.

Topics: Adult; Aged; Aged, 80 and over; Agranulocytosis; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aspartic Acid; Colorectal Neoplasms; Diarrhea; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Phosphonoacetic Acid; Survival Rate

In a randomized phase II study by the Cancer and Leukemia Group B, the cisplatin/5-fluorouracil/leucovorin (PFL) combination produced a 29% response rate in advanced, unresectable non-small cell lung cancer. Vinorelbine (Navelbine; Burroughs Wellcome, Co, Research Triangle Park, NC; Pierre Fabre Médicament, Paris, France), a semisynthetic vinca alkaloid, has also demonstrated single-agent activity in this disease. Therefore, a phase I-II study was designed to investigate the addition of vinorelbine in escalating doses to the PFL combination. The objectives of this study were to establish the maximum tolerated dose of vinorelbine in combination with PFL, and to define the overall response rate in a cohort of patients treated with the maximum tolerated dose. The regimen consisted of vinorelbine in escalating doses starting at 20 mg/m2/d intravenously on days 1 and 5, followed by leucovorin 100 mg orally every 4 hours on days 1 to 5,5-fluorouracil 800 mg/m2/d intravenous continuous infusion days 2 to 5 (96 hours), and cisplatin 100 mg/m2 intravenously 12 to 24 hours after administration of the first dose of vinorelbine. Cycles were repeated every 3 weeks. No dose-limiting toxicity was observed in the first five patients treated with the initial vinorelbine dose. Increasing the dose of vinorelbine to 25 mg/m2 in a second cohort of two patients, however, resulted in grade 4 granulocytopenia in both, and grade 4 diarrhea in one. It was concluded that this dose level was not feasible. During a preliminary analysis, one complete response and three partial responses were observed in 16 patients evaluated; one of these patients had a pathologic complete remission. This early analysis indicates activity for the regimen.

Topics: Adult; Aged; Agranulocytosis; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Carcinoma, Non-Small-Cell Lung; Cisplatin; Cohort Studies; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Remission Induction; Vinblastine; Vinorelbine

To determine the toxicities and potential for dose escalation of intravenous (IV) bolus fluorouracil (5-FU) given with 500 mg/m2/d leucovorin (LCV) and granulocyte-macrophage colony-stimulating factor (GM-CSF).. Thirty-seven patients received escalating doses of 5-FU/LCV on days 1 to 5 with subcutaneous GM-CSF either 5 or 10 micrograms/kg/d starting on day 6 or 3 micrograms/kg/d starting on day 1. 5-FU was escalated from 370 mg/m2/d by 15% increments between patient cohorts and within patients according to tolerance.. With GM-CSF starting on day 6, dose-limiting toxicity occurred during cycle no. 1 in all three patients entered at 5-FU 490 mg/m2/d. However, individual patients tolerated 5-FU doses up to 644 mg/m2/d. When all cycles were analyzed, grade 3 to 4 mucositis and grade 4 granulocytopenia complicated < or = 15% and < or = 6% of cycles with 5-FU doses < or = 560 mg/m2/d (115 cycles). With GM-CSF starting on day 1, dose-limiting granulocytopenia occurred during cycle no. 1 in five of 10 patients entered at 5-FU 490 mg/m2/d. Although the granulocyte nadirs were significantly lower at each 5-FU dose level with the concurrent GM-CSF schedule (eg, 490 mg/m2/d: median, 879/microL v3,286/microL; two-tailed P [P2] < .001), dose-limiting granulocytopenia complicated < or = 16% of cycles with 5-FU < or = 560 mg/m2/d (99 cycles); > or = grade 3 mucositis occurred in < or = 20% of cycles. Grade 3 to 4 diarrhea was unusual with either GM-CSF schedule. Most patients treated with GM-CSF > or = 5 micrograms/kg/d required dose reductions for constitutional toxicity; 3.0 to 3.8 micrograms/kg/d was better tolerated. Venous thrombosis occurred in 17% of patients (concurrent v sequential GM-CSF, 29% v 5%; P2 = .08). The median delivered 5-FU dose-intensity for GM-CSF starting either on day 6 or on day 1 was 615 and 647 mg/m2/wk (P2 = .41), respectively. Pharmacologic exposure to 5-FU increased with higher doses of 5-FU, and concurrent GM-CSF administration did not affect 5-FU clearance.. A starting dose of 425 mg/m2/d of 5-FU with LCV on days 1 to 5 could be safely combined with GM-CSF starting either on day 1 or day 6, with further 5-FU dose escalation according to individual tolerance.

Topics: Adenocarcinoma; Adult; Aged; Agranulocytosis; Drug Administration Schedule; Female; Fluorouracil; Gastrointestinal Neoplasms; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Leucovorin; Male; Middle Aged; Recombinant Proteins; Treatment Outcome

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

Topics: Adolescent; Adult; Aged; Agranulocytosis; Alopecia; Clinical Trials as Topic; Cyclophosphamide; Cytarabine; Drug Combinations; Female; Humans; Leucovorin; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Nervous System Diseases; Radiography, Thoracic; Remission, Spontaneous; Vincristine

Despite recent progress in the treatment of advanced urothelial cancer, there continues to be a need to identify new active agents and their toxicity spectra. We conducted a study using FOLFOX-4 (oxaliplatin, fluorouracil, folinic acid) in pre-treated advanced bladder cancer patients.. Sixteen eligible patients with advanced disease were treated with oxaliplatin (85 mg/m(3)) on day 1 followed by fluorouracil and folinic acid (De Gramont schedule) on days 1 and 2 every 14 days until disease progression. All patients received nutritional support to increase their caloric intake. Objective responses and toxicity were evaluated. Biochemical responses (reduction of markers) and nutritional parameters (increase in body weight and albumin, and reduction in ferritin and C-reactive protein) were also considered.. Three patients obtained an objective response (overall response rate 19%). Hematological toxicity and stomatitis were the most commonly noted side effects, but we observed only low (3-4) grade toxicity. In four patients (25%), we observed a reduction in tumoral markers (carcinoembryonic antigen and tissutal polypeptide antigen) and modified nutritional parameters.. Using these doses and schedules of FOLFOX-4 appears to be a promising therapy in patients pre-treated with platinum compounds. More studies are required to assess the possible role of this regimen in the treatment of advanced bladder cancer.

Topics: Aged; Aged, 80 and over; Agranulocytosis; Anemia; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Transitional Cell; Deoxycytidine; Drug Administration Schedule; Energy Intake; Female; Fluorouracil; Gemcitabine; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Stomatitis; Taxoids; Tissue Polypeptide Antigen; Urinary Bladder Neoplasms

Prospective randomized clinical trials have shown the effectiveness of combined adjuvant 5-fluorouracil-based chemotherapy and radiotherapy after surgical resection of rectal cancer. To assess toxicity of this therapy, prospective data were collected from 236 Asian rectal cancer patients treated with combined 5-fluorouracil-based chemotherapy and radiotherapy after surgery. Almost 82% of patients completed planned therapy. Grade 3 and 4 diarrhea, stomatitis, and granulocytopenia occurred in approximately 18-21% of patients. There were two treatment-related deaths from granulocytopenia and sepsis. With median follow-up of 3.5 years, median disease-free and overall survival was 75 and 88 months, respectively. In conclusion, combined adjuvant 5-fluorouracil-based chemotherapy and radiotherapy after surgical resection of rectal cancer is tolerable in Asian patients with moderate toxicity.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Agranulocytosis; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Combined Modality Therapy; Diarrhea; Disease-Free Survival; Drug Evaluation; Female; Fluorouracil; Humans; Leucovorin; Life Tables; Lymph Node Excision; Male; Middle Aged; Neoplasm Metastasis; Postoperative Period; Prospective Studies; Radiotherapy, Adjuvant; Rectal Neoplasms; Sepsis; Singapore; Stomatitis; Survival Analysis

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

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: 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