Carboplatin in small cell lung cancer: the Royal Marsden Hospital experience

A series of studies has been carried out to evaluate and document the value of carboplatin in the treatment of patients with small cell lung cancer (SCLC). Encouraging response rates but disappointingly short response durations with both single-agent carboplatin and combination carboplatin/etoposide led to the use of more intensive study regimens. A six-course, dose-intensive study of combination carboplatin/etoposide/ifosfamide in good-prognosis patients resulted in a 97% objective response rate (31 of 32 patients), including 17 (53%) complete responses. However, the toxicity associated with this regimen was expectedly high. In a subsequent phase I dose-escalation study of carboplatin in SCLC, non-small cell lung cancer, and mesothelioma, patients received 800, 1,200, or 1,600 mg/m2 carboplatin given as a 1-hour intravenous infusion. Five of the seven SCLC patients achieved a complete or partial response, but no responses were seen among the other patients. The major toxicity noted was myelosuppression and, while treatment was well tolerated, toxicity was more pronounced at the higher doses. The role of carboplatin as palliative therapy for SCLC patients with advanced disease or poor performance status is currently under investigation with a regimen containing carboplatin/methotrexate/vinblastine. In light of the results of these several studies, it is apparent that carboplatin is an extremely active agent for treatment of SCLC and is not associated with the nephropathy, neuropathy, or severe nausea and vomiting induced by its parent compound, cisplatin. Further study of carboplatin as high-dose therapy, in dose-intensive combination regimens, and as palliative treatment is recommended.