Risk-adapted adjuvant chemotherapy after concomitant fluoropyrimidine-radiotherapy neoadjuvant treatment for patients with resectable cT3-4 or N+ rectal cancer

Anticancer Drugs. 2011 Feb;22(2):185-90. doi: 10.1097/cad.0b013e328340fd02.

Abstract

Adjuvant chemotherapy in rectal cancer is not well defined.After neoadjuvant chemoradiation and surgery, at least a short period of treatment with 5-fluorouracil is recommended, and some investigators claim a more aggressive approach, in particular, for those patients with a high risk of systemic relapse. Nevertheless, there are few studies about adjuvant combination therapy tolerance and efficacy, and no randomized trials have been conducted comparing fluoropyrimidines versus combination therapy such as folinic acid plus 5-fluorouracil plus oxaliplatin(FOLFOX), considered the standard of care in stage IIIcolon cancer. We present an institutional series of risk adapted adjuvant therapy. Sixty evaluable patients who had received treatment with neoadjuvant fluoropyrimidine radiotherapy and surgery now received adjuvant fluoropyrimidines in the case of pT0-2N0 or oxaliplatin based combination in the case of pT3-4 or N+ . Overall, 33 patients experienced downstaging to pT2-0N0 (55%) and27 patients were restaged as pT3-4 or N+ (45%) after surgery. Local recurrence rate was 5% (three patients), one local and one local plus systemic in the adjuvant single agent group and one local plus systemic in the adjuvant FOLFOX group. Systemic relapse occurred in 14 patients(23.3%), five (15%) in the single-agent group and nine(33.3%) in the FOLFOX group. Disease-free survival at 3 years for patients in the good prognostic group(pT0-2N0) and poor prognostic group (pT3-4 or N+ ) were 78.7 and 62.2%, respectively. Severe diarrhoea was more frequent with fluoropyrimidines and neutropenia, mucositis and peripheral neuropathy were more common with FOLFOX. There were no toxic deaths. A risk-adapted adjuvant therapeutic decision is feasible with an acceptable safety profile even with the use of oxaliplatin based combinations. Three-year disease-free survival compares favourably with historical controls, especially in those patients with high risk factors for relapse.Phase III controlled trials are needed.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / radiotherapy*
  • Adenocarcinoma / surgery
  • Aged
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Capecitabine
  • Chemotherapy, Adjuvant
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / analogs & derivatives*
  • Fluorouracil / therapeutic use*
  • Humans
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Radiotherapy, Adjuvant
  • Rectal Neoplasms / drug therapy*
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / radiotherapy*
  • Rectal Neoplasms / surgery

Substances

  • Antimetabolites, Antineoplastic
  • Organoplatinum Compounds
  • Oxaliplatin
  • Deoxycytidine
  • Capecitabine
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol