CISPLATIN AND VP16 IN METASTATIC BREAST-CARCINOMA AS A 3RD-LINE CHEMOTHERAPY - A RANDOMIZED STUDY COMPARING LOW VERSUS HIGH-DOSES OF CISPLATIN

Aims and background: The study was designed to define the activity of the combination of cisplatin and etoposide as third-line chemotherapy for advanced breast cancer and to investigate the role of the dosage of cisplatin on the effectiveness of the combination, Methods: Ninety-five eligible patients with advanced breast cancer who had failed or relapsed on two previous lines of chemotherapy were randomized to receive cisplatin at a high dose (100 mg/m(2) i.v. day 1, arm A) or a low dose (60 mg/m(2) day 1, arm B), combined with etoposide (100 mg/m(2) i.v. days 4, 6 and 8), Cycles were repeated every 3 weeks. Results: Of the 78 patients evaluable for response (39 in arm A and 39 in arm B), 9 (12%) showed complete or partial response, 5 (13%) in the high-dose arm and 4 (10%) in the low-dose arm, One complete response was seen in the high-dose arm and none in the low-dose arm. The only 2 patients with brain involvement showed an objective response (one CR in arm A and one PR in arm B). Median time to progression was 14 weeks in arm A and 10 weeks in arm B, median duration of remission 28 and 34 weeks, and survival 36 and 35 weeks, respectively. The differences were not significant. As expected, the patients in the high-dose arm experienced more severe toxicity, One toxic death was observed in each arm due to sepsis in agranulocytosis. The difference was statistically significant regarding nausea and vomiting. Neurotoxicity and ototoxicity were not relevant problems in this patient setting. Conclusions: Considering the very poor prognostic factors presented by these patients, the combination showed a certain activity, and further evaluation in earlier stages of disease is warranted, A particular responsiveness on brain metastases is suggested, The dose of cisplatin was not proven to be of significant importance.