期刊
CANCER CHEMOTHERAPY AND PHARMACOLOGY
卷 71, 期 5, 页码 1191-1199出版社
SPRINGER
DOI: 10.1007/s00280-013-2113-1
关键词
PARP; DNA repair; Melanoma; Chemopotentiation; Phase II
资金
- Pfizer GRD
- Cancer Research UK
- UK Departments of Health through the Experimental Cancer Medicine Centre initiative
- Public Health Agency [SPI/3315/06] Funding Source: researchfish
poly(ADP ribose) polymerase inhibition has been shown to potentiate the cytotoxicity of DNA damaging agents. A phase I study of rucaparib and temozolomide showed that full-dose temozolomide could be given during PARP inhibition. We report the results of a phase II study of intravenous rucaparib 12 mg/m(2) and oral temozolomide 200 mg/m(2) on days 1-5 every 28 days in patients with advanced metastatic melanoma. Patients with chemotherapy na < ve measurable metastatic melanoma, performance status a parts per thousand currency sign2 and good end-organ function were recruited. Treatment was given until progression. A two stage phase II design was used, with response rate the primary endpoint. Population pharmacokinetics and pharmacodynamics were also explored. Forty-six patients were recruited with 37 patients receiving at least 2 cycles and 17 patients at least 6 cycles. Myelosuppression occurred with 25 patients (54 %) requiring a 25 % dose reduction in temozolomide. The response rate was 17.4 %, median time to progression 3.5 months, median overall survival 9.9 months, and 36 % of patients were progression-free at 6 months. This study showed that temozolomide (150-200 mg/m(2)/day) can safely be given with a PARP inhibitory dose of rucaparib, increasing progression-free survival over historical controls in metastatic melanoma patients.
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