Lookup NU author(s): Professor Ruth Plummer,
Dr Evan Mulligan,
Professor Nicola Curtin,
Professor Alan Calvert
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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.
Author(s): Plummer R, Lorigan P, Steven N, Scott L, Middleton MR, Wilson RH, Mulligan E, Curtin N, Wang D, Dewji R, Abbattista A, Gallo J, Calvert H
Publication type: Article
Publication status: Published
Journal: Cancer Chemotherapy and Pharmacology
Print publication date: 01/05/2013
Online publication date: 20/02/2013
Acceptance date: 05/02/2013
ISSN (print): 0344-5704
ISSN (electronic): 1432-0843
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