A phase I study of TPI 287 in combination with temozolomide for patients with metastatic melanoma
| Autor: | Suzanne Cain, Jennifer L. McQuade, Sapna Pradyuman Patel, Agop Y. Bedikian, Michael A. Davies, Srisuda Lecagoonporn, Roland L. Bassett, Patrick Hwu, Wen-Jen Hwu, Rodabe N. Amaria, Liberty Posada |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male Oncology Cancer Research medicine.medical_specialty Skin Neoplasms Metastatic melanoma Central nervous system Dermatology Article 03 medical and health sciences 0302 clinical medicine Stable Disease Internal medicine Antineoplastic Combined Chemotherapy Protocols Temozolomide medicine Humans 030212 general & internal medicine Antineoplastic Agents Alkylating Melanoma Aged Aged 80 and over Taxane business.industry Middle Aged medicine.disease Phase i study Dacarbazine medicine.anatomical_structure 030220 oncology & carcinogenesis Toxicity Female Taxoids business medicine.drug |
| Zdroj: | Melanoma Research. 26:604-608 |
| ISSN: | 0960-8931 |
| DOI: | 10.1097/cmr.0000000000000296 |
| Popis: | TPI 287 is a synthetic taxane derivative with structural modifications allowing for central nervous system penetration and potential circumvention of multidrug resistance efflux pump mechanisms. The aim of this phase I study was to determine the maximum tolerated dose of the combination of TPI 287 and temozolomide in metastatic melanoma. Patients with stage IV unresectable or recurrent stage III melanoma were eligible. Stable untreated or treated brain metastases were allowed. Patients with previous taxane exposure were excluded. TPI 287 was administered intravenously on days 1, 8, and 15 and temozolomide was taken orally daily on days 1-5 of a 28-day cycle. Responses were assessed every two cycles according to WHO criteria. A total of 21 patients were enrolled. The maximum tolerated dose of the combination at this schedule was determined to be 125 mg/m intravenous of TPI 287 and 110 mg/m of oral temozolomide. The dose-limiting toxicity was neuropathy and six patients experienced grade III neuropathy. All patients were evaluable for tumor response. There were no complete responses; there were two partial responses and seven patients had stable disease (overall response rate 9.5% and disease control rate 42.9%). Three patients had stable disease in the brain despite progressive extracranial disease. The combination of TPI 287 and temozolomide is well tolerated in patients with metastatic melanoma, with the exception of neuropathy. The central nervous system penetration of both agents makes this a rational combination for further testing in primary and metastatic brain lesions. |
| Databáze: | OpenAIRE |
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