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A Phase Ib Open-Label, Dose-Escalation Study of NUC-1031 in Combination with Carboplatin for Recurrent Ovarian Cancer.
Kazmi, Farasat; Nicum, Shibani; Roux, Rene L; Spiers, Laura; Gnanaranjan, Chat; Sukumaran, Ajithkumar; Gabra, Hani; Ghazaly, Essam; McCracken, Nigel W; Harrison, David J; Blagden, Sarah P.
Afiliação
  • Kazmi F; Early Phase Clinical Trials Unit, Department of Oncology, University of Oxford, Oxford, United Kingdom.
  • Nicum S; Churchill Hospital, Oxford University Hospitals Trust, Oxford, United Kingdom.
  • Roux RL; Churchill Hospital, Oxford University Hospitals Trust, Oxford, United Kingdom.
  • Spiers L; Early Phase Clinical Trials Unit, Department of Oncology, University of Oxford, Oxford, United Kingdom.
  • Gnanaranjan C; Barts Cancer Institute, London, United Kingdom.
  • Sukumaran A; Ovarian Cancer Action Research Centre, Imperial College London, London, United Kingdom.
  • Gabra H; Ovarian Cancer Action Research Centre, Imperial College London, London, United Kingdom.
  • Ghazaly E; School of Medicine, University of St Andrews, St Andrews, United Kingdom.
  • McCracken NW; NuCana plc, Edinburgh, United Kingdom.
  • Harrison DJ; School of Medicine, University of St Andrews, St Andrews, United Kingdom.
  • Blagden SP; NuCana plc, Edinburgh, United Kingdom.
Clin Cancer Res ; 27(11): 3028-3038, 2021 06 01.
Article em En | MEDLINE | ID: mdl-33741651
PURPOSE: NUC-1031 is a first-in-class ProTide modification of gemcitabine. In PRO-002, NUC-1031 was combined with carboplatin in recurrent ovarian cancer. PATIENTS AND METHODS: NUC-1031 was administered on days 1 and 8 with carboplatin on day 1 every 3 weeks for up to six cycles. Four dose cohorts of NUC-1031 (500, 625, and 750 mg/m2) with carboplatin (AUC4 or 5) were investigated. Primary endpoint was recommended phase II combination dose (RP2CD). Secondary endpoints included safety, investigator-assessed objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), and pharmacokinetics. RESULTS: A total of 25 women with recurrent ovarian cancer, a mean of 3.8 prior lines of chemotherapy, and a median platinum-free interval of 5 months (range: 7-451 days) were enrolled; 15 of 25 (60%) were platinum resistant, 9 (36%) were partially platinum sensitive, and 1 (4%) was platinum sensitive. Of the 23 who were response evaluable, there was 1 confirmed complete response (4%), 5 partial responses (17%), and 8 (35%) stable disease. The ORR was 26% and CBR was 74% across all doses and 100% in the RP2CD cohort. Median PFS was 27.1 weeks. NUC-1031 was stable in the plasma and rapidly generated high intracellular dFdCTP levels that were unaffected by carboplatin. CONCLUSIONS: NUC-1031 combined with carboplatin is well tolerated in recurrent ovarian cancer. Highest efficacy was observed at the RP2CD of 500 mg/m2 NUC-1031 on days 1 and 8 with AUC5 carboplatin day 1, every 3 weeks for six cycles. The ability to deliver carboplatin at AUC5 and the efficacy of this schedule even in patients with platinum-resistant disease makes this an attractive therapeutic combination.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Protocolos de Quimioterapia Combinada Antineoplásica / Carboplatina / Monofosfato de Citidina / Recidiva Local de Neoplasia Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Protocolos de Quimioterapia Combinada Antineoplásica / Carboplatina / Monofosfato de Citidina / Recidiva Local de Neoplasia Idioma: En Ano de publicação: 2021 Tipo de documento: Article