Phase II study of gemcitabine and carboplatin in metastatic breast cancers with prior exposure to anthracyclines and taxanes.

BACKGROUND: Patients with metastatic breast cancer (MBC) are usually exposed to both anthracyclines and taxanes during neoadjuvant or adjuvant treatment of primary breast cancer or during initial therapy of MBC. We investigate the combination of gemcitabine and carboplatin in MBC with prior exposure to both anthracyclines and taxanes. PATIENTS AND METHODS: MBC patients previously treated with anthracyclines and taxanes were enrolled in a single tertiary center phase II study. Treatment consisted of gemcitabine (1,000 mg/m(2) I.V on days 1 and 8) and carboplatin (AUC 5 I.V on day 1) administered every 3 weeks. Results 41 patients were recruited. Objective response rate was 39% including 1 complete response (2%) and 15 partial responses (37%). Twelve patients (29%) had stable disease. Median time to progression was 4.6 months (95% CI 3.3-5.9 months) and median overall survival 10.5 months (95% CI 7.6-13.4 months). Grade 3 & 4 hematological toxicities included neutropenia (58%), febrile neutropenia (15%), anemia (12%) and thrombocytopenia (49%), including 7% who required platelet transfusions. Non-hematological toxicity was rarely severe. 56% of patients required at least one dose reduction; the mean relative dose intensity for gemcitabine and carboplatin were 0.82 (range 0.5-1.0) and 0.95 (range 0.75-1.00) respectively, with no difference in dose intensity between responders and non-responders.
CONCLUSION: Gemcitabine combined with carboplatin has promising efficacy in MBC with prior treatment with anthracyclines and taxanes but has significant haematological toxicities requiring dose modifications. The regimen may be modified to gemcitabine 800 mg/m(2) days 1 and 8 to improve tolerability.