A PHASE-1 STUDY OF CARBOPLATIN AND ALPHA-2 INTERFERON IN PATIENTS WITH MALIGNANT PLEURAL EFFUSIONS

Although carboplatin shows interesting pharmacokinetic properties for intracavitary treatment, up to now no data on intrapleural administrat ion has been obtained. In order to evaluate the feasibility and the ma ximum tolerated dose of carboplatin administered by intrapleural route we performed a phase I study. In view of a possible phase II study we added interferon to carboplatin because preclinical data suggest a sy nergy between the two agents. Forty-four patients with malignant pleur al effusion, received carboplatin at doses of 150-950 mg every three w eeks and interferon alpha-2b at a dose of 20 million U, weekly. All pa tients but two completed at least two cycles of therapy and were consi dered evaluable for response. The maximum tolerated dose of carboplati n was identified at 850 mg, which corresponds to 400-450 mg/m2, accoun ting to the median body surface of our patients. Unacceptable toxicity was seen at 950 mg and consisted of the following grade 3-4 toxicity; thrombocytopenia in three patients; leukopenia in two patients and na usea/vomiting in one patient. Local toxicity was not present at any le vel. Interferon was reduced at 10 million U weekly after the first fou r patients because of severe systemic toxicity. Responses were seen at all dosage levels. 28 patients (12 non small cell lung carcinoma:NSCL C; 6 breast; 4 small cell lung carcinoma: SCLC; 2 mesothelioma; 2 stom ach; 1 ovary; 1 kidney) (63%; 95% Cl, 50% to 76%) responded, with 8 co mplete responses observed (3 NSCLC; 2 SCLC; 2 mesothelioma; 1 ovary). The median duration of response was 4 months. In conclusion, intrapleu ral administration of carboplatin and interferon seems to be safe and effective. The outcome of this study is sufficiently encouraging to te st this combination in a subsequent phase II study, using the dosage l evels defined as the maximum tolerated dose.