Overall side effect assessment of oxaliplatin toxicity in rectal cancer patients in NRG oncology/NSABP R04

Qual Life Res. 2024 Nov;33(11):3069-3079. doi: 10.1007/s11136-024-03746-5. Epub 2024 Jul 30.

Abstract

Purpose: Regulatory guidance suggests capturing patient-reported overall side effect impact in cancer trials. We examined whether the Functional Assessment of Cancer Therapy (FACT) GP5 item ("I am bothered by side effects of treatment") post-neoadjuvant chemotherapy/radiotherapy differed between oxaliplatin vs. non- oxaliplatin arms in the National Surgical Adjuvant Breast and Bowel Project (NSABP) R-04 trial of stage II-III rectal cancer patients.

Methods: The R-04 neoadjuvant trial compared local-regional tumor control between patients randomized to receive 5-fluorouracil or capecitabine with radiation, with or without oxaliplatin (4 treatment arms). Participants completed surveys at baseline and immediately after chemoradiotherapy. GP5 has a 5-point response scale: "Not at all" (0), "A little bit" (1), "Somewhat" (2), "Quite a bit" (3), and "Very much" (4). Logistic regression compared the odds of reporting moderate-high side effect impact (GP5 2-4) between patients receiving oxaliplatin or not after chemoradiotherapy, controlling for relevant patient characteristics. We examined associations between GP5 and other patient-reported outcomes reflecting side effects.

Results: Analyses were performed among 1132 study participants. Participants receiving oxaliplatin were 1.58 times (95% CI: 1.22-2.05) more likely to report moderate-high side effect bother at post-chemotherapy/radiation. In both arms, worse overall side effect impact was associated with patient-reported diarrhea, nausea, vomiting, and peripheral sensory neuropathy (p < 0.01 for all).

Conclusion: This secondary analysis of R-04 found that GP5 distinguished between patients receiving oxaliplatin or not as part of their post-neoadjuvant chemoradiotherapy, adding patient-centric evidence on the reduced tolerability of oxaliplatin and demonstrating that GP5 is sensitive to known toxicity differences between treatments.

Clinicaltrials: GOV: NCT00058474.

Keywords: Cancer; Clinical trials; FACT GP5; Treatment tolerability.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Capecitabine / administration & dosage
  • Capecitabine / adverse effects
  • Capecitabine / therapeutic use
  • Chemoradiotherapy / adverse effects
  • Drug-Related Side Effects and Adverse Reactions
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Fluorouracil / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Organoplatinum Compounds / therapeutic use
  • Oxaliplatin* / administration & dosage
  • Oxaliplatin* / adverse effects
  • Oxaliplatin* / therapeutic use
  • Quality of Life
  • Rectal Neoplasms* / drug therapy

Substances

  • Oxaliplatin
  • Fluorouracil
  • Capecitabine
  • Antineoplastic Agents
  • Organoplatinum Compounds

Associated data

  • ClinicalTrials.gov/NCT00058474