Development of peripheral neuropathy and its association with survival during treatment with nab-paclitaxel plus gemcitabine for patients with metastatic adenocarcinoma of the pancreas: A subset analysis from a randomised phase III trial (MPACT).

Abstract

BACKGROUND:

In a phase III trial in patients with metastatic pancreatic cancer (MPC), nab-paclitaxel plus gemcitabine (nab-P/Gem) demonstrated greater efficacy but higher rates of peripheral neuropathy (PN) versus Gem. This exploratory analysis aimed to characterise the frequency, duration, and severity of PN with nab-P/Gem in the MPACT study.

PATIENTS AND METHODS:

Patients with previously untreated MPC received nab-P/Gem or Gem. PN was evaluated using a broad-spectrum group of Standardised Medical Dictionary for Regulatory Activities Queries (SMQ) and graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0. A case report form was completed by physicians on day 1 of each cycle (also graded by NCI CTCAE version 3.0).

RESULTS:

In the nab-P/Gem arm, 227/421 patients (54%) experienced any-grade PN and 70 (17%) experienced grade III PN. No grade IV PN was reported. Most early-onset PN events were grade I, and treatment-related grade III PN occurred in 7% of patients who received up to three cycles of nab-P. Of those who developed grade III PN with nab-P/Gem treatment, 30 (43%) improved to grade ≤ I (median time to improvement = 29 days) and 31 (44%) resumed therapy. Development of PN was associated with efficacy; median overall survival in patients with grade III versus 0 PN was 14.9 versus 5.9 months (hazard ratio, 0.33; P < .0001).

CONCLUSIONS:

nab-P/Gem was associated with grade III PN in a small percentage of patients. PN development was associated with longer treatment duration and improved survival. Grade III PN was reversible to grade ≤ I in many patients (median ≈ 1 month) NCT00844649.

• Authors: David Goldstein, Daniel D Von Hoff, Malcolm Moore, Edward Greeno, Giampaolo Tortora, Ramesh K Ramanathan, Teresa Macarulla, Helen Liu, Richard Pilot, Stefano Ferrara, Brian Lu
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 52 Pg. 85-91 (Jan 2016) ISSN: 1879-0852 [Electronic] England
• PMID: 26655559 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• 130-nm albumin-bound paclitaxel
• Albumins
• Deoxycytidine
• Paclitaxel
• Gemcitabine

Topics

• Adenocarcinoma (drug therapy, mortality, secondary)
• Albumins (adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Deoxycytidine (adverse effects, analogs & derivatives)
• Humans
• Paclitaxel (adverse effects)
• Pancreatic Neoplasms (drug therapy, mortality, pathology)
• Peripheral Nervous System Diseases (chemically induced, diagnosis, mortality)
• Risk Assessment
• Risk Factors
• Severity of Illness Index
• Time Factors
• Treatment Outcome
• Gemcitabine