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

Strauss, SJ; Marples, M; Napier, MP; Meyer, T; Boxall, J; Rustin, GJS; (2003) A phase I (tumour site-specific) study of carboplatin and temozolomide in patients with advanced melanoma. Br J Cancer , 89 (10) pp. 1901-1905. 10.1038/sj.bjc.6601414.

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Abstract

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 x m(-2), with escalating doses of carboplatin AUC 3-6. In stage 2, patients received temozolomide 1000 mg x 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 x 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.

Type: Article
Title: A phase I (tumour site-specific) study of carboplatin and temozolomide in patients with advanced melanoma.
Location: England
DOI: 10.1038/sj.bjc.6601414
Keywords: Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Area Under Curve, Carboplatin, Dacarbazine, Drug Interactions, Female, Humans, Male, Maximum Tolerated Dose, Melanoma, Middle Aged, Skin Neoplasms, Temozolomide, Thrombocytopenia
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: http://discovery.ucl.ac.uk/id/eprint/104608
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