Weekly docetaxel with either gemcitabine or vinorelbine as second-line treatment in patients with advanced nonsmall cell lung carcinoma: Phase II trials of the Minnie Pearl Cancer Research Network.

BACKGROUND: The current study was conducted to evaluate the feasibility, toxicity, and efficacy of weekly docetaxel when paired with either gemcitabine or vinorelbine as the second-line treatment of patients with advanced nonsmall cell lung carcinoma. METHODS: Patients with progressive nonsmall cell lung carcinoma after one previous chemotherapeutic regimen, an Eastern Cooperative Oncology Group performance status of 0-2, and measurable lesions were eligible for treatment in these Phase II trials. Patients who had not received gemcitabine previously were treated with docetaxel, 30 mg/m(2), and gemcitabine, 800 mg/m(2), both of which were administered intravenously (i.v.) on Days 1, 8, and 15 of a 28-day cycle. If the patients had received gemcitabine as part of first-line therapy, they were treated with docetaxel, 30 mg/m(2), and vinorelbine, 20 mg/m(2) i.v., on Days 1, 8, and 15 of a 28-day cycle. Patients were reevaluated after two courses of treatment, and responding patients continued treatment for six courses or until disease progression. RESULTS: Forty patients were treated with a combination of docetaxel and gemcitabine, and 23 patients received docetaxel and vinorelbine. The docetaxel/gemcitabine combination was reasonably well tolerated, with moderate myelosuppression and a few nonhematologic toxicities reported. The objective response rate was 10%, with a 1-year survival rate of 20%. The docetaxel/vinorelbine combination was found to be poorly tolerated, with Grade 3/4 leukopenia reported in 71% of patients and neutropenic fever reported in 70% of patients despite frequent dose reductions and omission of the Day 15 doses. Enrollment onto this regimen was stopped prematurely due to toxicity, and after no major responses were observed in the first 20 evaluable patients. CONCLUSIONS: The combination of weekly docetaxel/gemcitabine appears to be feasible and relatively well tolerated as second-line treatment in patients with advanced nonsmall cell lung carcinoma, whereas a weekly combination of docetaxel and vinorelbine did not appear to be tolerable at the doses and schedule used in the current study. Neither regimen showed a level of activity that suggested any advantage compared with the results obtained with single-agent docetaxel in this setting.

Weekly docetaxel in the treatment of elderly patients with advanced breast cancer: a Minnie Pearl Cancer Research Network phase II trial.

PURPOSE: To evaluate the efficacy and toxicity of docetaxel administered weekly to elderly or poor-performance status patients with advanced breast cancer. PATIENTS AND METHODS: Forty-one patients with advanced breast cancer who were either over the age of 65 or considered to be poor candidates for combination chemotherapy received docetaxel 36 mg/m2 weekly for 6 consecutive weeks, followed by 2 weeks without treatment. The median age of patients in this trial was 74 years, and 73% of patients had one or more visceral sites of metastases. Seventy-five percent of patients received weekly docetaxel as first-line treatment for metastatic breast cancer, and the other 25% received it as second-line treatment. Thirty-six patients were assessable for efficacy, and all patients were assessed for toxicity. RESULTS: A total of 448 doses of weekly docetaxel were administered to 41 patients. Thirteen patients (36%) had objective responses to treatment, and an additional 13 patients (36%) had stable disease or minor response. Median time to progression for responding and stable patients was 7 months (range, 3 to 27 months). Median survival for the entire group was 13 months, with 1- and 2-year actuarial survival rates of 61% and 29%, respectively. Severe neutropenia occurred in only 0.4% of courses, and no other hematologic toxicity was observed. Grade 3/4 fatigue was the most common toxicity, occurring in 20% of patients. CONCLUSION: Weekly docetaxel therapy is active and well tolerated by elderly and/or poor-performance status patients with advanced breast cancer. This treatment can be administered with minimal myelosuppression. Weekly docetaxel provides an additional option for treatment in this difficult subgroup of patients with metastatic breast cancer. Well-tolerated combination regimens containing weekly docetaxel merit evaluation for this patient population.

Weekly docetaxel in the treatment of elderly patients with advanced nonsmall cell lung carcinoma. A Minnie Pearl Cancer Research Network Phase II Trial.

BACKGROUND: Weekly administration of docetaxel was found to reduce myelosuppression and other nonhematologic toxicities when compared with administration every 3 weeks. In the current Phase II trial, the authors evaluated the feasibility, toxicity, and efficacy of weekly docetaxel in the treatment of elderly patients with newly diagnosed advanced nonsmall cell lung carcinoma. METHODS: Thirty-nine patients with advanced, previously untreated nonsmall cell lung carcinoma entered this Phase II trial between February 1998 and January 1999. Patients were required either to be age >/= 65 years or to be poor candidates for combination chemotherapy due to coexistent medical illnesses. All patients received docetaxel, 36 mg/m(2), administered weekly for 6 consecutive weeks, followed by 2 weeks without treatment. Patients were reevaluated after 8 weeks of treatment; responding patients continued weekly docetaxel for a maximum of 32 weeks or until disease progression. RESULTS: Weekly docetaxel was well tolerated by this elderly group of patients with nonsmall cell lung carcinoma. Grade 3 leukopenia was noted in only 3 patients (8%), and no patient developed Grade 4 myelosuppression. Grade 3/4 nonhematologic toxicity also was uncommon; fatigue/asthenia was reported in 4 patients (10%). Seven of 38 evaluable patients (18%) had objective responses to weekly docetaxel whereas an additional 13 patients (34%) had a minor response or stable disease at first reevaluation. The median survival in this group of elderly patients was 5 months, with a 1-year actuarial survival rate of 27%. CONCLUSIONS: The results of the current study show that weekly docetaxel is active and well tolerated in elderly patients with advanced nonsmall cell lung carcinoma and provides an additional treatment option for these patients, who often tolerate combination chemotherapy regimens poorly.

Phase II trial of 9-aminocamptothecin administered as a 72-hour continuous infusion in metastatic colorectal carcinoma.

PURPOSE: The camptothecin derivative irinotecan has demonstrated clinical activity in metastatic colorectal carcinoma in both chemotherapy-naive and fluorouracil-refractory patients. 9-Aminocamptothecin (9-AC; NSC 603071), another camptothecin derivative, was selected for clinical development based on preclinical activity, including cures in human tumor xenografts resistant to standard anticancer agents. We report a phase II trial of 9-AC in patients with previously untreated metastatic colorectal carcinoma. PATIENTS AND METHODS: Colorectal cancer patients with measurable disease, a performance status of 0 to 2 (Zubrod), and no prior chemotherapy for metastatic disease received 9-AC. A cycle of therapy was 35 microg/m2/h for 72 consecutive hours (840 microg/m2/d for 3 days) and rest on days 4 to 14; a course of therapy was defined as two cycles (28 days). Patients were assessed for response after two courses. RESULTS: Seventeen patients with metastatic colorectal cancer were entered onto this trial. No complete or partial responses were noted. Treatment was well tolerated; toxic effects consisted mainly of neutropenia, nausea, vomiting, stomatitis, fatigue, and anemia. Grade 3 to 4 toxicity was limited to neutropenia (grade 3 in four patients and grade 4 in six), anemia (grade 3 in two patients), and vomiting (grade 3 in two patients). No grade 3 or 4 diarrhea occurred. Only two patients had their 9-AC dose reduced to 30 microg/m2/h. The median nadir absolute granulocyte count (AGC) was 1,500/microL. The median number of courses given was two and the median time to disease progression was 8 weeks. CONCLUSION: At the dose and schedule used in this trial, 9-AC lacked antitumor activity in metastatic colorectal cancer. 9-AC infusion schedules of longer duration are currently being investigated in this disease.

Phase II trial of merbarone in pancreatic carcinoma. A Southwest Oncology Group study.

Twenty-nine patients with advanced pancreatic adenocarcinoma were treated with merbarone, utilizing a daily intravenous schedule for 5 days. Only two partial responses of short duration were observed. The major toxicities were renal, with an increase in creatinine or proteinuria in 17 patients, and mild to moderate nausea and vomiting seen in 22 patients. Merbarone in this dose and schedule has minimal activity in pancreatic cancer.

Phase II study of amonafide in advanced pancreatic adenocarcinoma.

To determine the efficacy of amonafide in patients with advanced, measurable pancreatic adenocarcinoma, 15 patients previously untreated with chemotherapy were entered on a phase II trial. The starting dose was 400 mg/m2 administered daily over 1 hr for 5 consecutive days repeated every 3 weeks. Because of grade 4 myelosuppression observed in the initial 2 patients, the daily starting dose was decreased to 350 mg/m2. Of the 15 patients, 14 were evaluable. Amonafide failed to produce clinical responses in the doses and schedule employed. Grade 4 granulocytopenia was observed in 3 of 9 courses at 400 mg/m2, 3 of 12 courses at 350 mg/m2 and in 1 of 4 courses at 300 mg/m2. Grade 4 thrombocytopenia was observed in 3 courses at 400 mg/m2. Nonhematologic toxicities included mild nausea and vomiting and skin rashes.

Germ cell malignancies of the ovary: treatment with vinblastine, actinomycin D, bleomycin and cisplatin containing chemotherapy combinations.

Seventeen patients with malignant ovarian germ cell tumors were treated with vinblastine, actinomycin D, bleomycin and cisplatin containing combinations. Many of these patients were heavily pretreated. Thirteen patients had objectively measurable disease and ten (77%) had an objective response (CR or PR). Four patients had nonmeasurable disease or were treated in an adjuvant setting and all remain without evidence of disease. Extensive disease and poor performance status were poor prognostic factors. Induction portions of these treatment programs which contained cisplatin appeared most effective. Maintenance portions without cisplatin appeared less effective.