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)

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

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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.

Original languageEnglish (US)
Pages (from-to)85-91
Number of pages7
JournalEuropean Journal of Cancer
Volume52
DOIs
StatePublished - Jan 2016

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gemcitabine
Peripheral Nervous System Diseases
Pancreas
Adenocarcinoma
Survival
Therapeutics
National Cancer Institute (U.S.)
130-nm albumin-bound paclitaxel
Pancreatic Neoplasms
Terminology
Medical Dictionaries

Keywords

  • Gemcitabine
  • Pancreatic cancer
  • Peripheral neuropathy
  • nab-Paclitaxel

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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). / Goldstein, David; Von Hoff, Daniel D.; Moore, Malcolm; Greeno, Edward; Tortora, Giampaolo; Ramanathan, Ramesh K.; Macarulla, Teresa; Liu, Helen; Pilot, Richard; Ferrara, Stefano; Lu, Brian.

In: European Journal of Cancer, Vol. 52, 01.2016, p. 85-91.

Research output: Contribution to journalArticle

Goldstein, David ; Von Hoff, Daniel D. ; Moore, Malcolm ; Greeno, Edward ; Tortora, Giampaolo ; Ramanathan, Ramesh K. ; Macarulla, Teresa ; Liu, Helen ; Pilot, Richard ; Ferrara, Stefano ; Lu, Brian. / 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). In: European Journal of Cancer. 2016 ; Vol. 52. pp. 85-91.
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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.",
keywords = "Gemcitabine, Pancreatic cancer, Peripheral neuropathy, nab-Paclitaxel",
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T1 - Development of peripheral neuropathy and its association with survival during treatment with nab-paclitaxel plus gemcitabine for patients with metastatic adenocarcinoma of the pancreas

T2 - A subset analysis from a randomised phase III trial (MPACT)

AU - Goldstein, David

AU - Von Hoff, Daniel D.

AU - Moore, Malcolm

AU - Greeno, Edward

AU - Tortora, Giampaolo

AU - Ramanathan, Ramesh K.

AU - Macarulla, Teresa

AU - Liu, Helen

AU - Pilot, Richard

AU - Ferrara, Stefano

AU - Lu, Brian

PY - 2016/1

Y1 - 2016/1

N2 - 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.

AB - 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.

KW - Gemcitabine

KW - Pancreatic cancer

KW - Peripheral neuropathy

KW - nab-Paclitaxel

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