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Background

Irinotecan/5-FU/FA (I-FU) or 5-FU/FA (FU) first line therapy in older and younger patients with metastatic colorectal cancer: Combined analysis of 2,691 patients in randomized controlled trials.

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Background

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  1. Irinotecan/5-FU/FA (I-FU) or 5-FU/FA (FU) first line therapy in older and younger patients with metastatic colorectal cancer: Combined analysis of 2,691 patients in randomized controlled trials. G. Folprecht1, M. T. Seymour2, L. Saltz3, J.-Y. Douillard4, R. J. Stephens5, E. Van Cutsem6, P. Rougier7, T. S. Maughan8, C.-H. Köhne9 for the irinotecan metaanalysis group 1University hospital Dresden, Germany, 2Cancer Research UK Clinical Centre, Cookridge Hospital, Leeds, U.K., 3Memorial Sloan-Kettering Cancer Center, New York, U.S., 4Centre R. Gauducheau Saint Herblain, Nantes, France, 5MRC Clinical Trials Unit, London, U.K., 6University Hospital Gasthuisberg, Leuven, Belgium, 7Hopital Ambroise Paré, Boulogne, France, 8Velindre Hospital, Cardiff, U.K., 9Klinikum Oldenburg, Germany

  2. Background • Irinotecan has been shown to improve response rates and progression free survival in several randomized studies. One question is whether elderly patients benefint in the same extent from combination therapy as younger patients. • With 5-FU- therapy, pooled analyses describe a similar treatment benefit in elderly as in younger patients in palliative treatment (Folprecht 2004) and in adjuvant therapy (Sargent, NEJM 2001). • Although no increased toxicity was described in a analysis from the Royal Marsden hospital with palliative treatment of elderly patients, slightly higher rates of stomatitis (Popescu, JCO 1999) or leucocytopenia (Sargent, NEJM 2001) are reported in adjuvant 5-FU containing therapy. • A recent analysis by Goldberg et al (JCO 2006) showed that oxaliplatin- containing schedules have the similar toxicity and efficacy in elderly patients. Folprecht et al, ASCO 2007

  3. Methods • We updated a metaanalysis using source data of 5-FU/FA and 5-FU/FA/irinotecan arm of four randomized trials (Saltz 2000, Douillard 2000, Köhne 2005 [EORTC 40986], Seymour 2005 [FOCUS]) to explore the efficacy and toxicity in elderly patients (≥70 years) in comparison to younger patients (< 70 years). Randomized patients who did not receive therapy were excluded. • Differences in proportional values were investigated using the chi square test or Fisher’s exact test, where appropriated. For progression free survival or overall survival, Kaplan-Meier plots and log rank tests were used. A multivariate analysis including treatment (5-FU/FA vs. 5-FU/FA/irinotecan) and age (< 70 y. vs. ≥ 70y.) was performed. Folprecht et al, ASCO 2007

  4. Patients’ characteristics (I) Folprecht et al, ASCO 2007

  5. Patients’ characteristics (II) Folprecht et al, ASCO 2007

  6. Results: toxicity (I) Folprecht et al, ASCO 2007

  7. Results: toxicity (II) Folprecht et al, ASCO 2007

  8. Results: toxicity (III) Folprecht et al, ASCO 2007

  9. Results: Efficacy (I) Test of interaction between age and treatment: no interaction for PFS p=0.84, for OS p=0.61 (cox-regression analysis); no interaction between age and treatment on overall response rate; logistic regression analysis: p=0.33) Folprecht et al, ASCO 2007

  10. 5-FU/FA 5-FU/FA/Irinotecan ---- ≥ 70 years ── < 70 years Time to progression in 2,691 patients treated with 5-FU +/- irinotecan < 70 years ≥ 70 years ── 5-FU/FA/Iri ---- 5-FU/FA Folprecht et al, ASCO 2007

  11. 5-FU/FA 5-FU/FA/Irinotecan ---- ≥ 70 years ── < 70 years Overall survival in 2,691 patients treated with 5-FU +/- irinotecan < 70 years ≥ 70 years ── 5-FU/FA/Iri ---- 5-FU/FA Folprecht et al, ASCO 2007

  12. < 70 years ≥ 70 years ── 5-FU infus. / Iri - - - 5-FU bolus / Iri ── 5-FU infus. - - - 5-FU bolus Overall survival depending on 5-FU schedule in 2,691 patients treated with 5-FU +/- irinotecan Folprecht et al, ASCO 2007

  13. Conclusions • We could investigate a large cohort of fit elderly patients who received 5-FU monotherapy or irinotecan / 5-FU within clinical trials. • All conclusions are valid for patients only who are could be treated in clinical trial. • Response rates and progression free survival are significantly improved with irinotecan in elderly and younger patients. • Elderly patients have similar response rates, progression free and overall survival with irinotecan/5-FU/FA as younger patients do. There was no interaction between age and efficacy. • Although overall survival significantly is significantly improved with irinotecan in younger patients, no significant difference was observed in elderly patients. This could be explained by the lower patient number and by a trend to an unfavourable overall survival during the first treatment weeks with bolus 5-FU plus irinotecan which might be induced by the early mortality with the IFL- regimen (Rothenberg, JCO 2001). • Regarding all patients in this analysis, no major influence of age on toxicity was found. The only interaction between age and treatment was less vomiting with 5-FU in elderly patients and a trend to more hepatic toxicity in elderly patients. Folprecht et al, ASCO 2007

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