A phase I (tumour site-specific) study of carboplatin and temozolomide in patients with advanced melanoma

Temozolomide is an oral alkylating agent that readily crosses the blood–brain barrier and has activity in patients with advanced melanoma. Carboplatin is a convenient outpatient treatment that also has activity in patients with melanoma. The purpose of this study was to assess the safety of a combination of temozolomide and carboplatin, and provide preliminary evidence of efficacy. In all, 30 patients were treated in two stages. In stage 1, patients received temozolomide 750 mg m(−2), with escalating doses of carboplatin AUC 3–6. In stage 2, patients received temozolomide 1000 mg m(−2), with increasing doses of carboplatin until dose-limiting toxicity (DLT) was experienced. In stage 1, 12 patients received 33 cycles of treatment. No grade 3/4 haematological toxicity was experienced up to carboplatin AUC 6. In stage 2, 18 patients received 55 cycles of treatment. The DLT was haematological with grade 4 myelosuppression seen with carboplatin AUC 5. In all, 11 patients were treated with carboplatin AUC 4 to gain further information on toxicity. Myelosuppression remained significant and common with grade 4 thrombocytopenia experienced in 50% of cycles. Two of 28 patients (7%) assessable for efficacy achieved a partial response. None of the 11 patients with brain metastases responded to treatment. The addition of carboplatin to temozolomide 1000 mg m(−2) significantly adds to toxicity with frequent grade 3/4 myelosuppression. Preliminary information on efficacy demonstrates that it is unlikely that the combination can be given in doses sufficient to improve on the efficacy of temozolomide alone.