COMBINATION CHEMOTHERAPY WITH CISPLATIN, CARBOPLATIN, AND ETOPOSIDE IN ADVANCED MALIGNANCY - A PHASE-I TRIAL

Cisplatin and carboplatin are platinum-based chemotherapeutic agents w ith broad antitumor activity and significantly different toxicity prof iles. They are commonly used in combination with etoposide (VP-16) in chemotherapeutic regimens. We conducted a phase I trial using the comb ination of cisplatin, carboplatin, and etoposide in advanced malignanc y, aimed at delivering a higher dose intensity of active platinum spec ies while taking advantage of their nonoverlapping toxicities. Etoposi de was added because of its synergistic action with platinum compounds . The initial chemotherapy regimen consisted of carboplatin 180 mg/m(2 ) on day 1, cisplatin 70 mg/m(2) on day 1, and etoposide 60 mg/m(2) on days 1-3. Dose was escalated based on toxicity observed at each level and separately for patients with a previous history of chemotherapy a nd for those with no prior treatment. Thirty-six patients were entered in the study, and 33 were evaluable. Hematologic toxicity was dose li miting. Grade 3-4 leukopenia was noted in 22 of 33 (66%) patients and grade 3-4 thrombocytopenia was noted in 16 of 33 (48%). No serious ble eding complications occurred. There was one treatment-related death du e to neutropenic sepsis; Nonhematologic toxicity was mild and not dose limiting. Ototoxicity and nephrotoxicity were minimal. No complete re sponses (CR) occurred. Nine of 33 (27%) patients had objective respons es, including 3 patients with adenocarcinoma of the esophagus or gastr oesophageal junction who had filled prior chemotherapy. Fifteen of 33 (45%) patients had stable disease. The maximum tolerated dose varied f or patients who had received prior chemotherapy and for those who were previously untreated. For further studies, the recommended dosing for previously untreated patients is carboplatin 300 mg/m(2) on day 1, ci splatin 70 mg/m(2) on day 1, and etoposide 105 mg/m(2) on days 1-3. Th e recommended dosing for patients with a history of prior chemotherapy is carboplatin 220 mg/m(2) on day 1, cisplatin 70 mg/m(2) on day 1, a nd etoposide 75 mg/m(2) on days 1-3. The combination of cisplatin, car boplatin, and etoposide merits further testing in phase II trials.