Patients with pathological stage N2 rectal cancer treated with early adjuvant chemotherapy have a lower treatment failure rate

BMC Cancer. 2017 Mar 9;17(1):182. doi: 10.1186/s12885-017-3170-3.

Abstract

Background: In this era of oxaliplatin-based adjuvant therapy, the optimal sequence in which chemoradiotherapy should be administered for pathological stage N2 rectal cancer is unknown. The aim of this study was to investigate this sequence.

Methods: In the primary adjuvant concurrent chemoradiotherapy (A-CRT) group (n = 71), postoperative concurrent chemoradiotherapy was administered before adjuvant chemotherapy. In the primary adjuvant chemotherapy (A-CT) group (n = 43), postoperative concurrent chemoradiotherapy was administered during or after adjuvant chemotherapy. Postoperative radiotherapy comprised 45-50.4 Gy in 25-28 fractions. Concurrent chemotherapy comprised two cycles of oral capecitabine (1,600 mg/m2) on days 1-14 and 22-35. Patients receiving adjuvant chemotherapy with four or more cycles of XELOX (oxaliplatin plus capecitabine) or eight or more cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) were included.

Results: Between June 2005 and December 2013, data for 114 qualified rectal cancer patients were analyzed. The percentages of patients in whom treatment failed in the A-CRT and A-CT groups were 33.8% and 16.3%, respectively (p = 0.042). More patients had distant metastases in the A-CRT group than in the A-CT group (32.4% vs. 14.3%, p = 0.028). Multivariate analysis indicated that the sequence in which chemoradiotherapy was administered (A-CT vs. A-CRT) was an independent prognostic factor for both estimated disease-free survival [hazard ratio (HR) 0.345, 95% confidence interval (CI) 0.137-0.868, p = 0.024] and estimated distant metastasis-free survival (HR 0.366, 95% CI 0.143-0.938, p = 0.036).

Conclusions: In pathological stage N2 rectal cancer patients, administering adjuvant chemotherapy before chemoradiotherapy led to a lower rate of treatment failure, especially with respect to distant metastasis. Adjuvant chemotherapy prescribed as early as possible might benefit this cohort of patients in this era of oxaliplatin-based adjuvant therapy.

Keywords: Adjuvant chemoradiotherapy; Adjuvant chemotherapy; Rectal cancer; Sequence.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Capecitabine / administration & dosage
  • Capecitabine / therapeutic use
  • Chemoradiotherapy, Adjuvant / methods*
  • Chemotherapy, Adjuvant / methods*
  • Disease-Free Survival
  • Dose Fractionation, Radiation
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / therapeutic use
  • Humans
  • Leucovorin / administration & dosage
  • Leucovorin / therapeutic use
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Organoplatinum Compounds / administration & dosage*
  • Organoplatinum Compounds / therapeutic use
  • Oxaliplatin
  • Rectal Neoplasms / pathology*
  • Rectal Neoplasms / therapy*
  • Treatment Outcome
  • Young Adult

Substances

  • Organoplatinum Compounds
  • Oxaliplatin
  • Capecitabine
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol