Long-term results of the treatment of patients with mantle cell lymphoma with cladribine (2-CDA) alone (95-80-53) or 2-CDA and rituximab (N0189) in the North Central Cancer Treatment Group.

BACKGROUND: The objective of this study was to test cladribine (2-CDA) alone and in combination with rituximab in patients with mantle cell lymphoma (MCL). METHODS: Patients with MCL were treated on 2 sequential trials. In Trial 95-80-53, patients received 2-CDA as initial therapy or at relapse. In Trial N0189, patients received combination 2-CDA and rituximab as initial therapy. In both trials, 2-CDA was administered at a dose of 5 mg/m2 intravenously on Days 1 through 5 every 4 weeks for 2 to 6 cycles, depending on response. In Trial N0189, rituximab 375 mg/m2 was administered on Day 1 of each cycle. RESULTS: Results were reported for 80 patients. Twenty-six previously untreated patients and 25 patients who had recurrent disease with a median age of 68 years received single-agent 2-CDA. The overall response rate (ORR) was 81% with 42% complete responses (CRs) in the previously untreated group. The median progression-free survival (PFS) was 13.6 months (95% confidence interval [95% CI], 7.2-22.1 months), and 81% of patients remained alive at 2 years. The ORR was 46% with a 21% CR rate in the recurrent disease group. The median PFS was 5.4 months (95% CI, 4.6-13.1 months), and 36% of patients remained alive at 2 years. Twenty-nine eligible patients with a median age of 70 years received 2-CDA plus rituximab. The ORR was 66% (19 of 29 patient), and the CR rate was 52% (15 of 29 patients). The median duration of response for patients who achieved a CR had not been reached at the time of the current report, and only 3 of the patients who achieved a CR developed recurrent disease at a median follow-up of 21.5 months. CONCLUSIONS: 2-CDA had substantial single-agent activity in both recurrent and untreated MCL, and the results indicated that it may be administered safely to elderly patients. The addition of rituximab to 2-CDA may increase the duration of response.

A phase II trial of docetaxel and carboplatin as first-line chemotherapy for metastatic breast cancer: NCCTG study N9932.

OBJECTIVE: A phase II multi-institutional clinical trial conducted to evaluate the efficacy and tolerability of docetaxel and carboplatin as first-line therapy for women with metastatic breast cancer. METHODS: Patients had histologically confirmed metastatic breast cancer with at least one measurable lesion. Prior adjuvant chemotherapy was permitted, provided that at least 12 months had elapsed between any prior taxane and platinum therapy. Patients received docetaxel 75 mg/m(2) with carboplatin AUC 6 mg/ml.min every 21 days until disease progression or prohibitive toxicity. RESULTS: All 53 patients enrolled were evaluable for response and toxicity. Median number of cycles delivered was 6. Overall response rate was 60%, with 3 complete responses (6%) and 29 partial responses (54%). Median time to disease progression was 9.6 months. Median survival time was 20.4 months. Myelosuppression was the predominant toxicity, with grade 3 or 4 neutropenia occurring in 94% of patients and 15% of patients experiencing febrile neutropenia. The overall incidence (grades 1-3) of neurosensory toxicity was 57% and neuromotor toxicity was 25%, respectively, with grade 3 toxicity occurring in 4% of patients each. CONCLUSIONS: The combination of docetaxel and carboplatin is highly active in metastatic breast cancer. Prophylactic growth factor support is recommended in any further evaluation of this combination in the treatment of patients with breast cancer.

Phase II study of gemcitabine plus cisplatin in patients with metastatic breast cancer: a North Central Cancer Treatment Group Trial.

BACKGROUND: This 2-stage, phase II cooperative group trial examined the efficacy and toxicity of 1000 mg/m2 gemcitabine plus 25 mg/m2 cisplatin weekly for 3 weeks and repeated every 28 days for patients with previously treated metastatic breast cancer. METHODS: Eligible patients had to have measurable metastatic disease. Progression on prior treatment with at least 1 chemotherapy program for metastatic disease and 1 prior anthracycline and/or taxane-containing regimen in either the metastatic or adjuvant setting was required. Patients who had received more than 2 chemotherapy treatments were not eligible for this study. RESULTS: Fifty-eight eligible patients were entered on this 2-stage study. A 38% incidence of grade 4 thrombocytopenia observed in the first stage of accrual required lowering the chemotherapy doses to 800 mg/m2 gemcitabine plus 20 mg/m2 cisplatin weekly for the first 3 weeks of a 4-week cycle during the second stage of the study. The overall response rate was 29% (95% confidence interval [CI], 11-52%) among patients receiving the original study dose and 32% (95% CI, 18-50%) for patients receiving the lower dose. In the original- and lower-dose groups, median time to progression was 30.7 weeks (95% CI, 12.7-43.4 weeks) and 26.0 weeks (95% CI, 19.0-32.1 week), respectively. Median survival of the original- and low-dose groups was 67.9 weeks (95% CI, 42.3-90.6 weeks) and 54.1 weeks (95% CI, 41.6-73.6 weeks), respectively. Hematologic toxicities were more manageable in the lower-dose group, whereas the nonhematologic toxicity profile was similar in the 2 dose groups. CONCLUSIONS: The response rate of this combination of gemcitabine and cisplatin is similar to that reported by other investigators but may not differ substantially from reports with single-agent gemcitabine in this patient population. The original dose level we used had unacceptable toxicity, which required lowering the doses of both gemcitabine and cisplatin by 20% to achieve acceptable toxicity and preserve clinical activity.