Weekly paclitaxel with epirubicin as second-line therapy of metastatic breast cancer: results of a clinical phase II study.

Phase I/II trials have shown that combination of an anthracycline with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) represents a high-potency therapy for treatment of patients with metastatic breast cancer, with response rates exceeding 90%. This phase II trial was conducted to test the tolerability and efficacy of weekly epirubicin plus paclitaxel as second-line therapy for patients with pretreated metastatic breast cancer. In this study, 35 patients with previous hormone therapy and/or chemotherapy were treated at a weekly dose of paclitaxel 80 mg/m2 with epirubicin 35 mg/m2 (10 patients, 123 cycles) or paclitaxel 80 mg/m2 with epirubicin 25 mg/m2 (25 patients, 218 cycles). The dose reduction of anthracyclines became necessary due to severe hemotoxicity (neutropenia World Health Organization grade 3 to 4 in 30.2% of cycles). The therapy schema included a 2-week therapy interval after each treatment period of 6 weeks, with treatment continued until response or disease progression. Overall, 18 patents (51.4%) presented with responses (complete response or partial response) to therapy, with seven (20%) achieving a complete response after six to 18 cycles. In three cases (8.6%), tumor state was unchanged for a median interval of 11 weeks (range, 5 to 20 weeks). Progressive disease was observed in seven cases (20%), and seven patients (20%) were not evaluable. Following epirubicin dose reduction, neutropenia World Health Organization grade 3 to 4 occurred in only 18.1% of cycles. Referring to nonhematologic toxicity, alopecia exceeded World Health Organization grade 2. Other nonhematologic toxicities exceeding grade 2 were observed in only a few courses and were not statistically relevant. No clinically relevant deterioration of cardiac function was observed at a median cumulative dose of epirubicin 285 mg/m2 (maximum cumulative dose, 630 mg/m2). This study has substantiated that the schedule used is highly efficient and well tolerated as second-line chemotherapy for patients with metastatic breast cancer.

Chemotherapy-induced severe thrombocytopenia in gynecologic oncology and its treatment with interleukin-3.

Six patients suffering from various gynecologic malignancies developed severe thrombocytopenia (WHO IV) after normal-dose chemotherapy. All patients were treated with platelet transfusions but the results on hematopoietic recovery were not satisfactory. Therefore treatment with a new hematopoietic substance (rh interleukin-3) was initiated. All patients received a dosage of 5 mu g/kg/bw daily s.c. up to 10 days depending on the response of platelet counts. In two women, who had suffered from severe hemorrhage (epistaxis resp. ankle joint hematoma), symptoms disappeared after approximately three days of rhIL-3 use. Whereas platelet transfusions were ineffective in all patients, IL-3 led to a significant increase of the platelet count after 3-5 days of application. Side-effects were mild, when seen in one case, where G-CSF was given at the same time. Our experience supports the idea of using new growth factors like rhIL-3 to cure chemotherapy-induced myelosuppression, such as severe thrombocytopenia.