Phase II study of cisplatin, 5-FU, and allopurinol in advanced esophageal cancer

Forty patients with advanced squamous cell carcinoma of the esophagus were treated with a combination of cisplatin, 5-FU (by continuous 5-day infusion), and allopurinol; 37 are evaluable for response. Thirteen remissions (35%) were obtained, including three complete and ten partial, with a median duration of 9 months. After chemotherapy, seven responding patients underwent a surgical procedure, which was radical in four. The most frequent side effects were nausea and vomiting. This regimen is effective and can be included in a multimodality approach.     

Phase III study of 5-FU and carmustine versus 5-FU, carmustine, and doxorubicin in advanced gastric cancer

Seventy-seven patients with advanced gastric carcinoma were prospectively randomized to receive 5-FU and carmustine (FB) with or without doxorubicin (FAB). Thirty-five patients were evaluable for response. Neither the response rates (partial remission, 11% for FB and 24% for FAB) nor survival times (median, 4.0 months for FB and 5.5 months for FAB) were statistically different. The median survival of patients with partial remission (7.8 months) and those with no change (7.4 months) was significantly prolonged compared to patients with progressive disease (4.5 months). The side effects of both regimens after the first treatment cycle (except alopecia in FAB) were low. After the second cycle more pronounced myelosuppression in the FAB arm was observed.     

Combination chemotherapy of cisplatin and 5-FU in advanced colorectal carcinoma

Thirty-two patients with advanced colorectal carcinoma were treated with cisplatin (100 mg/m2) by infusion over 24 hours on Day 1 and 5-FU (1000 mg/m2/day) by infusion over 24 hours on Days 2-6 every 28 days. Ten of the 32 patients had received prior chemotherapy consisting of either 5-FU alone or 5-FU combination regimens. Objective response was observed in 13 patients (two complete and 11 partial responses). Another 11 patients had stabilization of disease. The overall median survival time in this study was 9.53 months. Toxicity was generally mild and tolerable. The response rate found in this study indicated that continuous infusion of cisplatin-5-FU administered at this dose and schedule was moderately active in advanced colorectal carcinoma.     

Use of cisplatin, doxorubicin, and cyclophosphamide to treat advanced and recurrent adenocarcinoma of the endometrium

Eighteen patients with recurrent or advanced adenocarcinoma of the endometrium were treated with the combination of cisplatin, doxorubicin, and cyclophosphamide between January 1981 and December 1983. Sixteen of the 18 had received prior irradiation. None of the patients had received prior chemotherapy. Fifteen patients had previously received hormones without response. No patients received concurrent hormone treatments. Ten of the 18 patients (56%) achieved an objective response: five (28%) achieved complete response and five (28%) achieved partial response. Myelosuppression was present in seven patients, and two developed neurotoxicity. Combination chemotherapy using cisplatin, doxorubicin, and cyclophosphamide is active in patients with adenocarcinoma of the endometrium, including those who have received prior irradiation and have failed hormonal therapy.     

Epirubicin,cisplatin, and protracted infusion of 5-FU (ECF) in advanced intrahepatic cholangiocarcinoma

Purpose Intrahepatic cholangiocarcinoma usually presents late in the clinical course and has a poor prognosis. No effective systemic therapy is currently available. This study aimed to determine the efficacy and toxicity of the ECF regimen (epirubicin, cisplatin. and 24-h continuous infusion of 5-FU) in advanced intrahepatic cholangiocarcinoma.Patients and method On day 1, epirubicin 50 mg/m² and cisplatin 60 mg/m² were administered i.v., repeated every 21 days. 5-FU (200 mg/m²/day was given continuous i.v. via an ambulatory infusion pump throughout the treatment course. A total of 24 patients (15 men and nine women) with advanced intrahepatic cholangiocarcinoma between August 1996 and April 2002 were enrolled in this study.Results Of the 20 evaluable patients, two had partial response (10%) and nine had stable disease (45%), including two minor response. Grade 3/4 neutropenia was observed in six patients, while grade 3/4 thrombocytopenia was seen in five patients. There was no neutropenic infection or thrombocytopenic bleeding during any of the cycles of chemotherapy.Conclusion ECF regimen is well-tolerated but is not an effective treatment for advanced intrahepatic cholangiocarcinoma. Newer clinical trials with combination drugs should be developed.     

Phase II evaluation of doxorubicin plus cisplatin in advanced thyroid cancer: a Southeastern Cancer Study Group Trial

Twenty-two evaluable patients with all cell types of advanced thyroid cancer were treated with the combination of doxorubicin (60 mg/m2) plus cisplatin (60 mg/m2). There were two brief partial remissions (9.1%). There was considerable toxicity, with one drug-related death. Combination chemotherapy as given in this study was not effective for this patient population.     

Phase I study of docetaxel, cisplatin and concurrent radiotherapy for locally advanced gastric adenocarcinoma

This phase I study is designed to determine the maximal tolerated dose and the dose-limiting toxicity of docetaxel with cisplatin and concurrent radiotherapy in patients with unresectable locally advanced gastric adenocarcinoma. Docetaxel was given once a week with the dosage escalated from 5 mg/m(2) to 15 mg/m(2) in increments of 2.5 mg/m(2). Cisplatin were administered at 20 mg/m(2) once a week. Radiotherapy was delivered to 50.4Gy at 1.8Gy/day. At least three patients were enrolled at each level. The maximal tolerated dose (MTD) and dose-limiting toxicity (DLTs) was determined. The DLTs were defined as grade 3 or 4 hematologic and nonhematologic toxicity. Twenty-one patients with locally advanced gastric adenocarcinoma were enrolled. Grade 1-2 neutropenia and nausea/vomiting were the most common side effects. The first DLT (grade-3 neutropenia) was observed in one of three patients at 12.5 mg/m(2) docetaxel. Three more patients were enrolled, but DLT was not observed and 6 patients were enrolled into 15 mg/m(2) group, DLT occurred in 3 patients (1 Grade 3 neutropenia, 1 Grade 4 neutropenia and 1 Grade 3 nausea/vomiting). Overall tumor response rate was 66.7% with 28.6% complete and 38.1% partial response. In conclusion, the MTD of docetaxel was 15 mg/m(2), and the recommended dose of docetaxel for Phase II study was 12.5 mg/m(2) weekly. The docetaxel and cisplatin with concurrent radiotherapy were tolerable and feasible in treating locally advanced gastric adenocarcinoma.     

Phase II study of doxorubicin versus epirubicin in advanced breast cancer

Doxorubicin and its epimerized analog epirubicin were tested at a dose of 75 mg/m2 given iv every 3 weeks to 42 patients with advanced breast cancer, 23 of whom were in relapse from prior cyclophosphamide, methotrexate, and 5-FU (CMF) chemotherapy. The median cumulative dose was 540 mg/m2 (range, 225-650) for doxorubicin and 565 mg/m2 (range, 150-600) for epirubicin. Complete plus partial response was documented in 11 of 21 patients (52%) following doxorubicin and in 13 of 21 patients (62%) following epirubicin. The median observation period was 22 months (range, 14-30); the median duration of response and the median survival were superimposable. Doxorubicin and epirubicin exhibited a superior response rate in previously untreated patients [six of eight (75%) vs eight of 11 (73%)] compared to those previously given CMF with or without endocrine therapy [five of 13 (38%) vs five of ten (50%)]. Vomiting, mucositis, and leukopenia were documented less frequently following administration of epirubicin as compared to doxorubicin. Regarding cardiac evaluation, no significant differences were evident between the two drugs. However, a significant fall in the left ventricular ejection fraction was documented in women who received doxorubicin following a cumulative dose greater than 550 mg/m2. Following completion of doxorubicin therapy at cumulative doses of 580 and 562 mg/m2, two women developed left ventricular failure at 6 and 14 months, respectively. Epirubicin appears to be an effective drug for the treatment of breast cancer and, given at equal doses, is less toxic than doxorubicin.