Nab-Paclitaxel, Capecitabine, and Radiation Therapy After Induction Chemotherapy in Treating Patients With Locally Advanced and Borderline Resectable Pancreatic Cancer: Phase 1 Trial and Imaging-based Biomarker Validation.

Authors

Eugene J Koay
Mohamed Zaid
Maureen Aliru
Polycarpe Bagereka
Arie Van Wieren
Maria Jovie Rodriguez
Galia Jacobson
Robert A Wolff
Michael Overman
Gauri Varadhachary
Shubham Pant
Huamin Wang
Ching-Wei Tzeng
Naruhiko Ikoma
Michael Kim
Jeffrey E Lee
Matthew Hg Katz
Eric Tamm
Priya Bhosale
Cullen M Taniguchi
Emma B Holliday
Grace L Smith
Ethan B Ludmir
Bruce D Minsky
Christopher H Crane
Albert C Koong
Prajnan Das
Xuemei Wang
Milind Javle
Sunil Krishnan

Publication Date

11-1-2022

Journal

International Journal of Radiation Oncology, Biology, Physics

Abstract

PURPOSE: Effective consolidative chemoradiation (CRT) regimens are lacking. In this phase 1 trial, we evaluated the safety and efficacy of nab-paclitaxel, capecitabine, and radiation therapy after 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, underwent computed tomography-imaging, received a diagnosis of LAPC or BRPC, and received induction chemotherapy. Standard 3 + 3 study design was used, with 3 escalating nab-paclitaxel dose levels (50, 75, and 100 mg/m

RESULTS: Twenty-three patients started and finished on protocol (LAPC = 14, BRPC = 9). No grade 3 and 4 toxicities were reported in level 1 (n = 3) or level 2 (n = 3) initial groups. Two patients in the initial level 3 group developed dose limiting toxicity, establishing level 2 dose as the maximal tolerated dose. 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 = .004) and PFS (P = .03) compared with type II IR.

CONCLUSIONS: We established the maximum tolerated dose for nab-paclitaxel in a consolidative CRT regimen for pancreatic ductal adenocarcinoma. Preliminary efficacy results warrant phase 2 trial evaluation. IR may be used for personalized treatment.

Keywords

Albumins, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Capecitabine, Carcinoma, Pancreatic Ductal, Deoxycytidine, Humans, Induction Chemotherapy, Paclitaxel, Pancreatic Neoplasms

Comments

PMID: 35863672