RESUMO
BACKGROUND: Study 10, a four-part Phase 1/2 study, evaluated oral rucaparib monotherapy in patients with advanced solid tumours. Here we report the final efficacy and safety results in heavily pretreated patients with ovarian cancer who received rucaparib in Study 10 Parts 2A and 2B. METHODS: Parts 2A and 2B (Phase 2 portions) enrolled patients with relapsed, high-grade, platinum-sensitive or platinum-resistant, BRCA-mutated ovarian cancer who had received 2-4 (Part 2A) or 3-4 (Part 2B) prior chemotherapies. Patients received oral rucaparib 600 mg twice daily (starting dose). The primary endpoint was the investigator-assessed objective response rate (ORR) by RECIST v1.1. RESULTS: Fifty-four patients were enrolled: 42 in Part 2A (all had platinum-sensitive disease) and 12 in Part 2B (4 with platinum-sensitive disease; 8 with platinum-resistant disease). ORR was 59.3% (95% CI 45.0-72.4%). The median time to onset of the most common nonhaematological treatment-emergent adverse events (TEAEs) was typically early (<56 days) and was later for haematological TEAEs (53-84 days). The median duration of grade ≥3 TEAEs was ≤13 days. CONCLUSIONS: In patients with relapsed, platinum-sensitive or platinum-resistant germline BRCA-mutant high-grade ovarian cancer who had received ≥2 prior chemotherapies, rucaparib had robust antitumour activity with a safety profile consistent with prior reports. CLINICAL TRIAL REGISTRATION: NCT01482715.
Assuntos
Proteína BRCA2 , Neoplasias Ovarianas , Humanos , Feminino , Proteína BRCA2/genética , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/genética , Platina/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genéticaRESUMO
The characteristics of patients currently abusing controlled-release (CR) oxycodone admitted for inpatient detoxification were ascertained from medical record review of 48 inpatients with CR oxycodone dependence. Patients were categorized according to the manner in which they initially received the drug: illicitly or by prescription for legitimate medical use. Fifteen of the 48 patients (31%) initially obtained a CR oxycodone prescription legitimately for a medical condition. While none of these 15 patients had a history of prior opioid misuse, they were more likely than illicit CR oxycodone users to report prior detoxifications (P<0.03) as well as a lower mean age of first alcohol use (legitimate=11.7 versus illicit=14.7, P<0.05) and first illicit drug use (legitimate=12.8 versus illicit=15.8, P<0.05). These findings suggest that a history of substance abuse is common among patients abusing CR oxycodone, including individuals for whom CR oxycodone was initially legitimately prescribed for pain.