Long-term results of a phase II trial of high-dose radiotherapy (60 Gy) and UFT/l-leucovorin in patients with non-resectable locally advanced rectal cancer (LARC)

Acta Oncol. 2008;47(3):428-33. doi: 10.1080/02841860701798866.

Abstract

Background: Preoperative radiochemotherapy is a cornerstone in patients with non- resectable locally advanced rectal cancer (LARC). To improve outcome (number of R0 resections and survival) high-dose radiotherapy (RT) was combined with oral UFT/l-leucovorin to allow tumour regression before radical intended surgery.

Methods: Pelvic RT was delivered with megavoltage photons using a 5 field technique. RT was CT-based, given 5 days a week through one posterior field and two lateral fields (48.6 Gy/27 fractions) to encompass the primary tumour and the regional lymph nodes. In addition, the tumour bed received a concurrent boost (5.4 Gy/27 fractions) and a final boost (6 Gy/3 fractions); thus GTV received 60 Gy/30 fractions. Concurrent with RT patients received a daily dose of oral UFT 300 mg/m(2) plus l-leucovorin 22.5 mg 5/7 days (divided in three doses).

Results: From September 2000 to November 2004, 52 patients (median age 60 years (32-83); median PS 0 (0-2)) with LARC (36 primary, 16 recurrent) were included in this phase II study. All but three patients received the planned 60 Gy, median duration of RT was 42 days (25-49). Toxicity was very modest; only four patients had a dose reduction of UFT. No hematological toxicity of clinical significance was seen. Non-hematological toxicity grade 1 (GI-toxicity, fatigue and/or dysuria) was frequently observed but only four patients experienced grade 3 toxicity (diarrhoea and/or nausea/vomiting). Forty patients (77%) were operated (30 R0, 5 R1, 5 R2) median 55 days (27-112) after completion of RT. Seven (13%) patients had a pathological complete response (pCR). Thirty-one patients (60%) died after median 25.4 months (1.6-45.2 months). Twenty-one patients (40%) are still alive June 2007.

Conclusions: Preoperative high-dose RT and concomitant UFT produces major regression in most patients with non-resectable LARC and thus a good chance of cure.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / radiotherapy
  • Adenocarcinoma / surgery
  • Adenocarcinoma / therapy*
  • Adult
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemotherapy, Adjuvant / adverse effects
  • Dose Fractionation, Radiation
  • Drug Combinations
  • Female
  • Gastrointestinal Diseases / etiology
  • Hematologic Diseases / etiology
  • Humans
  • Leucovorin / therapeutic use
  • Male
  • Middle Aged
  • Neoadjuvant Therapy* / adverse effects
  • Preoperative Care
  • Radiotherapy, Adjuvant / adverse effects
  • Radiotherapy, High-Energy* / adverse effects
  • Rectal Neoplasms / drug therapy
  • Rectal Neoplasms / radiotherapy
  • Rectal Neoplasms / surgery
  • Rectal Neoplasms / therapy*
  • Survival Analysis
  • Tegafur / adverse effects
  • Tegafur / therapeutic use*
  • Treatment Outcome
  • Uracil / adverse effects
  • Uracil / therapeutic use*

Substances

  • Antimetabolites, Antineoplastic
  • Drug Combinations
  • UFT(R) drug
  • Tegafur
  • Uracil
  • Leucovorin