Clinical consequences of chemotherapy dose reduction in obese patients with stage III colon cancer: A retrospective analysis from the PETACC 3 study

Eur J Cancer. 2018 Aug:99:49-57. doi: 10.1016/j.ejca.2018.05.004. Epub 2018 Jun 15.

Abstract

Background: Dose reduction in obese cancer patients has been replaced by fully weight-based dosing recommendations. No data, however, are available on the effects of dose reduction in obese stage III colon cancer patients undergoing adjuvant chemotherapy.

Methods: Survival outcomes and toxicity data of obese (body mass index [BMI] ≥30 kg/m2), stage III colon cancer patients treated within the phase III PETACC 3 trial comparing leucovorin, 5-FU (LV5FU2) with LV5FU2 plus irinotecan were analysed retrospectively according to chemotherapy dosing at first infusion (i.e. fully weight-based dosed - versus dose-reduced group). Multivariate analyses on relapse free survival (RFS) and overall survival (OS) were conducted to adjust for baseline prognostic factors using Cox regression model.

Results: 13.4% (280 of 2094 patients) had a BMI ≥ 30 kg/m2, and 5.3% had both a BMI ≥ 30 kg/m2 and a body surface area (BSA) ≥2 m2. Dose reductions occurred in 16.1% of patients with a BMI ≥ 30 kg/m2 and 32.4% with BMI ≥ 30 kg/m2 and BSA ≥ 2 m2, respectively. In patients with BMI ≥ 30 kg/m2, multivariate analysis demonstrated a trend towards better RFS in the fully dosed compared to the dose-reduced group (Hazard ratio (HR): 0.69, 95% CI: 0.43-1.09; p = 0.11); however, there was no statistically significant difference in OS. In patients with BMI ≥ 30 kg/m2 and BSA ≥ 2 m2, multivariate analysis demonstrated better RFS in fully dosed compared with dose-reduced patients (HR: 0.48, 95% CI: 0.27-0.85; p = 0.01) and a strong trend towards better OS (HR: 0.53, 95% CI: 0.28-1.01; p = 0.052). This group comprised predominantly of men.

Conclusions: Data support the recommendation of using fully dosed chemotherapy for the adjuvant treatment in obese patients with colon cancer.

Keywords: Adjuvant chemotherapy; Body surface area; Colon cancer; Dosing; Obesity.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adenocarcinoma / complications
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy*
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / standards
  • Body Mass Index
  • Body Surface Area
  • Chemotherapy, Adjuvant / adverse effects
  • Chemotherapy, Adjuvant / methods
  • Chemotherapy, Adjuvant / standards
  • Colectomy
  • Colon / pathology
  • Colon / surgery
  • Colonic Neoplasms / complications
  • Colonic Neoplasms / mortality
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / therapy*
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Drug Dosage Calculations
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / prevention & control
  • Neoplasm Staging
  • Obesity / complications*
  • Practice Guidelines as Topic
  • Prognosis
  • Retrospective Studies
  • Sex Factors
  • Young Adult