Oxaliplatin-containing Preoperative Therapy in Locally Advanced Rectal Cancer: Local Response, Toxicity and Long-term Outcome

Clin Oncol (R Coll Radiol). 2016 Aug;28(8):532-9. doi: 10.1016/j.clon.2016.01.014. Epub 2016 Feb 14.

Abstract

Aims: This non-randomised study was undertaken to examine oxaliplatin as possibly an intensifying component of sequential neoadjuvant therapy in locally advanced rectal cancer for improved local and metastatic outcome.

Materials and methods: Ninety-seven patients (57 T2-3 cases, 40 T4 cases) received two cycles of the Nordic FLOX regimen (oxaliplatin 85 mg/m(2) day 1 and bolus 5-fluorouracil 500 mg/m(2) and folinic acid 100 mg days 1 and 2) before long-course chemoradiotherapy with concomitant oxaliplatin and capecitabine, followed by pelvic surgery. Treatment toxicity, local tumour response and long-term outcome were recorded.

Results: Good histologic tumour regression was obtained in 72% of patients. Implementing protocol-specific dose adjustments, tolerance was acceptable and 95% of patients received the total prescribed radiation dose. Estimated 5 year progression-free and overall survival were 61% and 83%, respectively. T4 stage was associated with an inferior local response rate, which again was highly associated with impaired long-term outcome.

Conclusions: In this cohort of rectal cancer patients dominated by T4 and advanced T3 cases given sequential oxaliplatin-containing preoperative therapy with acceptable toxicity, high tumour response rates and overall survival were obtained, consistent with both local and systemic effects. However, tumour response and long-term outcome remained inferior for a significant number of T4 cases, suggesting that the T4 entity is biologically heterogeneous with subgroups of patients eligible for further individualisation of therapy.

Keywords: 5-fluorouracil; chemoradiotherapy; locally advanced rectal cancer; neoadjuvant chemotherapy; oxaliplatin.

Publication types

  • Clinical Trial

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Capecitabine / administration & dosage
  • Capecitabine / adverse effects
  • Chemoradiotherapy / adverse effects
  • Chemoradiotherapy / methods
  • Disease Progression
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Humans
  • Leucovorin / administration & dosage
  • Leucovorin / adverse effects
  • Male
  • Middle Aged
  • Neoadjuvant Therapy / adverse effects
  • Neoadjuvant Therapy / methods*
  • Neoplasm Staging
  • Organoplatinum Compounds / administration & dosage*
  • Organoplatinum Compounds / adverse effects
  • Oxaliplatin
  • Rectal Neoplasms / drug therapy*
  • Rectal Neoplasms / mortality
  • Rectal Neoplasms / pathology
  • Treatment Outcome

Substances

  • Organoplatinum Compounds
  • Oxaliplatin
  • Capecitabine
  • Leucovorin
  • Fluorouracil