Clinical Study

British Journal of Cancer (2005) 93, 896–904. doi:10.1038/sj.bjc.6602800 www.bjcancer.com
Published online 11 October 2005

Modulation of 5-fluorouracil as adjuvant systemic chemotherapy in colorectal cancer: the IGCS-COL multicentre, randomised, phase III study

S De Placido1, M Lopez2, C Carlomagno1, G Paoletti2, S Palazzo3, L Manzione4, C Iannace5, G P Ianniello6, F De Vita7, C Ficorella8, A Farris9, G Pistillucci10, M Gemini11, E Cortesi12, V Adamo13, N Gebbia14, S Palmeri15, C Gallo16, F Perrone17, G Persico18 and A R Bianco1

  1. 1Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università Federico II, Napoli, Italy
  2. 2Struttura Complessa, Oncologia Medica B, Istituto Nazionale Tumori Regina Elena, Roma, Italy
  3. 3Divisione di Oncologia, Ospedale Mariano Santo, Cosenza, Italy
  4. 4U.O. di Oncologia Medica, Ospedale San Carlo, Potenza, Italy
  5. 5Divisione di Chirurgia Generale, Ospedale Moscati, Avellino, Italy
  6. 6U.O. di Oncologia, ASL-1, Benevento, Italy
  7. 7Divisione di Oncologia Medica, Seconda Università, Napoli, Italy
  8. 8Divisione di Oncologia Medica, Università de L'Aquila, Italy
  9. 9Divisione di Oncologia Medica, Università di Sassari, Italy
  10. 10Divisione di Oncologia, Ospedale S. Maria Goretti, Latina, Italy
  11. 11U.O. di Oncologia, Ospedale Belcolle, Viterbo, Italy
  12. 12U.O. Complessa Oncologia 'B' Università La Sapienza, Roma, Italy
  13. 13Dipartimento di Oncologia medica, A.O.U. Policlinico, Messina, Italy
  14. 14U.O. di Oncologia, Dipartimento di Oncologia Clinica, Università di Palermo, Italy
  15. 15Cattedra di Oncologia, Dipartimento di Oncologia Clinica, Università di Palermo, Italy
  16. 16Dipartimento di Medicina Pubblica, Clinica e Preventiva, Seconda Università, Napoli, Italy
  17. 17Unità Operativa Sperimentazioni Cliniche, Istituto Nazionale Tumori, Napoli, Italy
  18. 18Dipartimento Universitario di Chirurgia Generale, Geriatrica, Oncologica e Tecnologie Avanzate, Università Federico II, Napoli, Italy

Correspondence: Professor S De Placido, Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università Federico II, Via Sergio Pansini, 5, Napoli 80131, Italy. E-mail: sdponco@unina.it

Revised 2 August 2005; Accepted 25 August 2005.

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Abstract

The aims of this multicentre, randomised phase III trial were to evaluate: (1) the role of levamisol (LEV); and (2) the role of folinic acid (FA), added to 5-fluorouracil (5FU) in the adjuvant treatment of colorectal cancer. Patients with histologically proven, radically resected stage II or III colon or rectal cancer were eligible. The study had a 2 times 2 factorial design with four treatment arms: (a) 5FU alone, (b) 5FU+LEV, (c) 5FU+FA, (d) 5FU+LEV+FA, and two planned comparisons, testing the role of LEV and of FA, respectively. From March 1991, to September 1998, 1327 patients were randomised. None of the two comparisons resulted in a significant disease-free (DFS) or overall (OAS) survival advantage. The hazard ratio (HR) of relapse was 0.89 (95% confidence intervals (CI): 0.73–1.09) for patients receiving FA and 0.99 (95% CI 0.80–1.21) for those receiving LEV; corresponding HRs of death were 1.02 (95% CI: 0.80–1.30) and 0.94 (95% CI 0.73–1.20). Nonhaematological toxicity (all grade vomiting, diarrhoea, mucositis, congiuntivitis, skin, fever and fatigue) was significantly worse with FA, while all other toxicities were similar. In the present trial, there was no evidence that the addition of FA or LEV significantly prolongs DFS and OAS of radically resected colorectal cancer patients.

Keywords:

adjuvant chemotherapy, colorectal cancer, 5-fluorouracil modulation