T Aparicio1, S Lavau-Denes2, J M Phelip3, E Maillard4, J L Jouve5, D Gargot6, M Gasmi7, C Locher8, X Adhoute9, P Michel10, F Khemissa11, T Lecomte12, J Provençal13, G Breysacher14, J L Legoux15, C Lepère16, J Charneau17, J Cretin18, L Chone19, A Azzedine20, O Bouché21, I Sobhani22, L Bedenne23, E Mitry24. 1. Department of Gastroenterology, CHU Avicenne, APHP and University Paris 13, Sorbonne Paris Cité, Bobigny thomas.aparicio@avc.aphp.fr. 2. Department of Oncology, CHU Dupuytren, Limoges. 3. Department of Gastroenterology, CHU Saint Etienne-Hôpital Nord, Saint Priest en Jarez. 4. FFCD Data Center, Fédération Francophone de Cancérologie Digestive, Dijon. 5. Department of Gastroenterology, CHU Le Bocage, Dijon. 6. Department of Gastroenterology, CH Blois, Blois. 7. Department of Gastroenterology, CHU Hôpital Nord, Marseille. 8. Department of Gastroenterology, CH Meaux, Meaux. 9. Department of Gastroenterology, CHU Haut Lévèque, Pessac. 10. Department of Gastroenterology, CHU Charles Nicolle, Rouen. 11. Department of Gastroenterology, CH Saint Jean, Perpignan. 12. Department of Gastroenterology, CHU Trousseau, Tours. 13. Department of Oncology, CH Chambery, Chambery. 14. Department of Gastroenterology, CH Pasteur, Colmar. 15. Department of Gastroenterology, CH de la Source, Orléans. 16. Department of Digestive Oncology, CHU Georges Pompidou, APHP, Paris. 17. Department of Gastroenterology, CH Duchenne, Boulogne sur Mer. 18. Department of Oncology, Clinique Bonnefon, Alès. 19. Department of Gastroenterology, CHU Nancy, Vandoeuvre-les-Nancy. 20. Department of Gastroenterology, CH Avignon, Avignon. 21. Department of Gastroenterology, CHU Robert Debré, Reims. 22. Department of Gastroenterology, CHU Henri Mondor, APHP, Créteil. 23. FFCD Data Center, Fédération Francophone de Cancérologie Digestive, Dijon Department of Gastroenterology, CHU Le Bocage, Dijon. 24. Department of Oncology, Institut Curie, Saint-Cloud University Versailles-St Quentin, St Quentin, France.
Abstract
BACKGROUND: Metastatic colorectal cancer (mCRC) frequently occurs in elderly patients. However, data from a geriatric tailored randomized trial about tolerance to and the efficacy of doublet chemotherapy (CT) with irinotecan in the elderly are lacking. The benefit of first-line CT intensification remains an issue in elderly patients. PATIENTS AND METHODS: Elderly patients (75+) with previously untreated mCRC were randomly assigned in a 2 × 2 factorial design (four arms) to receive 5-FU (5-fluorouracil)-based CT, either alone (FU: LV5FU2 or simplified LV5FU2) or in combination with irinotecan [IRI: LV5FU2-irinotecan or simplified LV5FU2-irinotecan (FOLFIRI)]. The CLASSIC arm was defined as LV5FU2 or LV5FU2-irinotecan and the SIMPLIFIED arm as simplified LV5FU2 or FOLFIRI. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), safety and objective response rate (ORR). RESULTS: From June 2003 to May 2010, 71 patients were randomly assigned to LV5FU2, 71 to simplified LV5FU2, 70 to LV5FU2-irinotecan and 70 to FOLFIRI. The median age was 80 years (range 75-92 years). No significant difference was observed for the median PFS: FU 5.2 months versus IRI 7.3 months, hazard ratio (HR) = 0.84 (0.66-1.07), P = 0.15 and CLASSIC 6.5 months versus SIMPLIFIED 6.0 months, HR = 0.85 (0.67-1.09), P = 0.19. The ORR was superior in IRI (P = 0.0003): FU 21.1% versus IRI 41.7% and in CLASSIC (P = 0.04): CLASSIC 37.1% versus SIMPLIFIED 25.6%. Median OS was 14.2 months in FU versus 13.3 months in IRI, HR = 0.96 (0.75-1.24) and 15.2 months in CLASSIC versus 11.4 months in SIMPLIFIED, HR = 0.71 (0.55-0.92). More patients presented grade 3-4 toxicities in IRI (52.2% versus 76.3%). CONCLUSION: In this elderly population, adding irinotecan to an infusional 5-FU-based CT did not significantly increase either PFS or OS. Classic LV5FU2 was associated with an improved OS compared with simplified LV5FU2. CLINICALTRIALSGOV: NCT00303771.
BACKGROUND: Metastatic colorectal cancer (mCRC) frequently occurs in elderly patients. However, data from a geriatric tailored randomized trial about tolerance to and the efficacy of doublet chemotherapy (CT) with irinotecan in the elderly are lacking. The benefit of first-line CT intensification remains an issue in elderly patients. PATIENTS AND METHODS: Elderly patients (75+) with previously untreated mCRC were randomly assigned in a 2 × 2 factorial design (four arms) to receive 5-FU (5-fluorouracil)-based CT, either alone (FU: LV5FU2 or simplified LV5FU2) or in combination with irinotecan [IRI: LV5FU2-irinotecan or simplified LV5FU2-irinotecan (FOLFIRI)]. The CLASSIC arm was defined as LV5FU2 or LV5FU2-irinotecan and the SIMPLIFIED arm as simplified LV5FU2 or FOLFIRI. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), safety and objective response rate (ORR). RESULTS: From June 2003 to May 2010, 71 patients were randomly assigned to LV5FU2, 71 to simplified LV5FU2, 70 to LV5FU2-irinotecan and 70 to FOLFIRI. The median age was 80 years (range 75-92 years). No significant difference was observed for the median PFS: FU 5.2 months versus IRI 7.3 months, hazard ratio (HR) = 0.84 (0.66-1.07), P = 0.15 and CLASSIC 6.5 months versus SIMPLIFIED 6.0 months, HR = 0.85 (0.67-1.09), P = 0.19. The ORR was superior in IRI (P = 0.0003): FU 21.1% versus IRI 41.7% and in CLASSIC (P = 0.04): CLASSIC 37.1% versus SIMPLIFIED 25.6%. Median OS was 14.2 months in FU versus 13.3 months in IRI, HR = 0.96 (0.75-1.24) and 15.2 months in CLASSIC versus 11.4 months in SIMPLIFIED, HR = 0.71 (0.55-0.92). More patients presented grade 3-4 toxicities in IRI (52.2% versus 76.3%). CONCLUSION: In this elderly population, adding irinotecan to an infusional 5-FU-based CT did not significantly increase either PFS or OS. Classic LV5FU2 was associated with an improved OS compared with simplified LV5FU2. CLINICALTRIALSGOV: NCT00303771.