Nab-Paclitaxel, Capecitabine, and Radiation Therapy Following Induction Chemotherapy in Treating Patients with Locally Advanced and Borderline Resectable Pancreatic Cancer: Phase I Trial and Imaging-based Biomarker Validation
Mené sur 23 patients atteints d'un adénocarcinome canalaire du pancréas localement avancé ou à la limite de la résécabilité, cet essai de phase I évalue l'innocuité et l'efficacité d'un traitement associant nab-paclitaxel, capécitabine et radiothérapie après une chimiothérapie d'induction
Purpose: Effective consolidative chemoradiation (CRT) regimens are lacking. In this phase I trial, we evaluated the safety and efficacy of nab-paclitaxel, capecitabine, and radiation therapy (RT) following induction chemotherapy in patients with locally-advanced and borderline-resectable pancreatic cancer (LAPC and BRPC). Also, we evaluated a computed tomography (CT)-based biomarker of response. Methods and Materials: Eligible patients had pathologically-confirmed pancreatic ductal adenocarcinoma (PDAC), underwent CT-imaging, were diagnosed with LAPC or BRPC, and received induction chemotherapy. Standard 3+3 study design was used, with three escalating nab-paclitaxel dose levels (50, 75 and 100 mg/m2) with concurrent capecitabine and RT in cohort sizes of three starting at the lowest dose. Dose limiting toxicity (DLT) was defined as grade 3 or higher toxicity. Patients were restaged 4-6 weeks post-CRT completion, and surgical resection was offered to those with stable/ responsive disease. We scored the tumor interface response (IR) post-chemotherapy and post-CRT into type I (remained/ became more defined) and type II (became less defined). Overall survival (OS) and progression-free survival (PFS) from time of CRT were estimated using Kaplan-Meier method. p≤0.05 was considered significant. Results: Twenty-three patients started and finished on protocol (LAPC=14, BRPC=9). No grade III/IV toxicities were reported in level-1 (n=3) or level-2 (n=3) initial groups. Two patients in the initial level-3 group developed DLTs, establishing level 2 dose as the maximal tolerated dose (MTD). Level-2 group was expanded for additional 15 patients (for a total of 23 on trial), 5 of whom developed grade 3 toxicities. Seven patients underwent surgical resection. Median OS and PFS were 21.2 and 8.1 months, respectively. Type I IR was associated with better OS (p=0.004) and PFS (p=0.03) compared to type II IR. Conclusion: We established the MTD for nab-paclitaxel in a consolidative CRT regimen for PDAC. Preliminary efficacy results warrant phase II trial evaluation. IR may be used for personalized treatment.
International Journal of Radiation Oncology, Biology, Physics 2022