Carboplatin plus gemcitabine repeating doublet therapy in recurrent breast cancer.

PURPOSE: The combination of cisplatin plus gemcitabine is active in metastatic breast cancer. Carboplatin plus gemcitabine, widely used in ovarian and non-small-cell lung cancers, has also been used in breast cancer. This trial examined the efficacy and toxicity of split-dose carboplatin plus gemcitabine in advanced breast cancer. PATIENTS AND METHODS: Patients with measurable disease, recurrent after adjuvant and < or = 1 previous treatment for systemic disease, received carboplatin area under the curve = 2.0 (Calvert) plus gemcitabine 800 mg/m2, both drugs administered days 1 and 8 every 21 days. Of 15 patients accrued, 13 are fully evaluable. RESULTS: There were 2 complete (13.3%) and 6 partial (40%) responses, for an overall response rate by intention to treat of 53.3% (95% CI, 28%-82%). The median time to progression was 4.5 months (95% CI, 2.03-6.97 months), and median overall survival was 28.8 months (95% CI, 9.4-48.2 months). There were 2 patients with grade 3 (13.3%) anemia, 7 patients with grade 3 (46.6%) and 4 patients (26.6%) with grade 4 neutropenia, 4 patients with grade 3 (26.6%) and 3 patients (20%) with grade 4 thrombocytopenia. CONCLUSION: The repeating doublet of split-dose carboplatin plus gemcitabine reveals activity comparable to that of cisplatin plus gemcitabine, is well tolerated, and warrants evaluation in patients with recurrent breast cancer.

Phase II trial of gemcitabine plus cisplatin repeating doublet therapy in previously treated, relapsed ovarian cancer patients.

OBJECTIVES: The aim was to determine the safety and efficacy of gemcitabine plus cisplatin for patients with relapsed ovarian carcinoma and to compare ex vivo drug sensitivity profiles with clinical outcomes. PATIENTS AND METHODS: Previously treated patients with ovarian carcinoma received cisplatin (30 mg/m(2)) plus gemcitabine (600-750 mg/m(2)) on Days 1 and 8 of each 21-day cycle. Seventeen of the 27 patients underwent ex vivo analyses for correlation with clinical response. RESULTS: Of 27 patients, there were 7 (26%) complete and 12 (44%) partial responses, for an overall response rate of 70% (95% CI: 53-87%). Toxicities included neutropenia Grade III in 51.9%, Grade IV in 29.6%; anemia Grade III in 18.5 %; thrombocytopenia Grade III in 66.7 %, Grade IV in 29.6%; nausea and vomiting Grade III in 14.8 %; peripheral neuropathy Grade III in 3.7%; and alopecia Grade IV in 11.1% of patients. The median time to progression for objective responders was 7.9 months with a range of 2.1 to 13.2 months. There were no treatment-related deaths. Ex vivo results correlated with response, time to progression, and survival, remaining significant when adjusted for platin-resistance and number of prior therapies. Adjustment for platin-free interval decreased the significance but did not, in and of itself, predict significantly for progression-free survival. CONCLUSIONS: Cisplatin plus gemcitabine is active for patients with relapsed ovarian cancer. Toxicities, primarily hematologic, are manageable with dose modifications. Responses observed in heavily pretreated and platin-resistant patients indicate activity in drug-refractory patients. The results of the ex vivo analyses correlate with clinical outcomes.