Phase I study of olaparib in combination with liposomal doxorubicin in patients with advanced solid tumours.
Br J Cancer
; 111(4): 651-9, 2014 Aug 12.
Article
em En
| MEDLINE
| ID: mdl-25025963
ABSTRACT
BACKGROUND:
Olaparib, an oral PARP inhibitor, has shown antitumour activity as monotherapy in patients with germline BRCA1/2 (gBRCA)-mutated breast and ovarian cancer. This study evaluated olaparib capsules in combination with liposomal doxorubicin (PLD) in patients with advanced solid tumours (NCT00819221).METHODS:
Patients received 28-day cycles of olaparib, continuously (days 1-28) or intermittently (days 1-7), plus PLD (40 mg m(-2), day 1); seven olaparib dose cohorts (50-400 mg bid) were explored to determine the recommended dose. Assessments included safety, pharmacokinetics, pharmacodynamics and preliminary efficacy (objective response rate (ORR)).RESULTS:
Of 44 patients treated (ovarian, n=28; breast, n=13; other/unknown, n=3), two experienced dose-limiting toxicities (grade 3 stomatitis and fatal pneumonia/pneumonitis (200 mg per 28-day cycle); grade 4 thrombocytopenia (400 mg per 7-day cycle)). The maximum tolerated dose was not reached using continuous olaparib 400 mg bid plus PLD. Grade ≥3 and serious AEs were reported for 27 (61%) and 12 (27%) patients, respectively. No major pharmacokinetic interference was observed between olaparib and PLD. The ORR was 33% (n=14 out of 42; complete response, n=3). A total of 13 responders had ovarian cancer 10 were platinum-sensitive, 11 had a gBRCA mutation.CONCLUSIONS:
Continuous/intermittent olaparib (up to 400 mg bid) combined with PLD (40 mg m(-2)) was generally tolerated and showed evidence of antitumour activity in ovarian cancer.
Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Neoplasias da Mama
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Protocolos de Quimioterapia Combinada Antineoplásica
Tipo de estudo:
Clinical_trials
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Br J Cancer
Ano de publicação:
2014
Tipo de documento:
Article