Phase I Trial of nab-Paclitaxel Administered Concurrently With Radiotherapy in Patients With Locally Advanced Inoperable Pancreatic Adenocarcinoma

Amitesh Chandra Roy, M. Nazim Abbas, Timothy Jay Price, Nimit Singhal, Sina Vatandoust, John Leung, Ganessan Kichenadasse, Bogda Koczwara, Shawgi Sukumaran, Rajiv Kumar, Richard Woodman, Alex Scott-Hoy, Christos Stelios Karapetis

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives Nab-paclitaxel has radiosensitizing antitumor efficacy in pancreatic cancer. We aimed to establish maximum tolerated dose (MTD) of nab-paclitaxel with radiotherapy in unresectable locally advanced pancreatic cancer. Methods In a phase I dose escalation trial patients received weekly nab-paclitaxel for 6 weeks with external beam radiotherapy (EBRT). 3 + 3 design was used with nab-paclitaxel doses: 25 mg/m2 (cohort 1), 50 mg/m2 (cohort 2), 75 mg/m2 (cohort 3), and 100 mg/m2 (cohort 4). Primary endpoint was MTD. Secondary objectives were progression-free survival and overall survival. Results Fourteen patients were recruited. Median age was 69 years (range, 40-86). Grade 1/2 toxicities were nausea (93%), vomiting (54%), diarrhea (57%), and fatigue (69%). There were no dose limiting toxicities (DLT) in cohorts 1 to 3. In cohort 4, DLTs of febrile neutropenia and enterocolitis were observed in patient 1. Subsequent DLT of febrile neutropenia and enterocolitis occurred in patient 5 in the expanded cohort. Following chemoradiotherapy median progression-free survival was 4.7 months (95% confidence interval, 2.5-27.5) and median overall survival was 10.8 months (95% confidence interval, 6.37-25.2). Conclusions Nab-paclitaxel and EBRT was well-tolerated at doses below 100 mg/m2. The MTD and recommended phase II study dose for nab-paclitaxel with EBRT is 75 mg/m2 in this disease.

Original languageEnglish
Pages (from-to)490-495
Number of pages6
JournalPancreas
Volume51
Issue number5
DOIs
Publication statusPublished - May 2022

Keywords

  • locally advanced pancreatic cancer
  • nab-paclitaxel
  • radiotherapy

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