A Phase 1b trial of prexasertib in combination with chemoradiation in patients with locally advanced head and neck squamous cell carcinoma.
Radiother Oncol
; 157: 203-209, 2021 04.
Article
em En
| MEDLINE
| ID: mdl-33577866
ABSTRACT
BACKGROUND AND PURPOSE:
This study explored the feasibility of safely combining prexasertib, with cisplatin-radiotherapy (Part A) or cetuximab-radiotherapy (Part B) in patients with previously untreated, locoregionally advanced head and neck squamous cell carcinoma (HNSCC). MATERIALS ANDMETHODS:
Escalating doses of prexasertib were administered in each combination using a modified Time-to-Event Continual Reassessment Method. Pharmacokinetic (PK) analysis was performed using standard non-compartmental methods of analysis. Antitumor activity was evaluated using RECIST version 1.1.RESULTS:
In Part A, 7 patients received 20 mg/m2 prexasertib and cisplatin-radiotherapy. This dose exceeded the maximum tolerated dose (MTD); no other prexasertib dose was assessed. In Part B, 18 patients received prexasertib (20-40 mg/m2) and cetuximab-radiotherapy. The 30 mg/m2 dose of prexasertib was determined as the MTD. Febrile neutropenia was the dose-limiting toxicity in each arm. Most common treatment-emergent adverse events with both combinations were neutropenia, thrombocytopenia, dysphagia, stomatitis, dry mouth, anemia, radiation skin injury [reported term radiation dermatitis], and nausea. PK of prexasertib was consistent with previously published data following prexasertib monotherapy. Overall response rate in Parts A and B was 71.4% and 83.3%, respectively. The small number of patients and follow-up limits the interpretation of efficacy data.CONCLUSION:
This study did not establish a safe dose of cisplatin-radiotherapy. However, it demonstrates the proof-of-principle that prexasertib could be safely combined with cetuximab-radiotherapy. These data will provide the basis to leverage the potential radio-sensitization properties of a CHK1 inhibitor in combination with radiation or other targeted agents in a variety of therapeutic settings.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias de Cabeça e Pescoço
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article