Oxaliplatin-based first-line chemotherapy is associated with improved overall survival compared to first-line treatment with irinotecan-based chemotherapy in patients with metastatic colorectal cancer – Results from a prospective cohort study

Abstract

Norbert Marschner,1 Dirk Arnold,2 Erik Engel,3 Ulrich Hutzschenreuter,4 Jacqueline Rauh,5 Werner Freier,6 Holger Hartmann,7 Melanie Frank,8 Martina Jänicke7 On behalf of the TKK Registry Group 1Praxis für Interdisziplinäre Onkologie und Hämatologie, 2Klinik für Tumorbiologie, Freiburg, Germany; 3Hämatologisch – Onkologische Praxis Altona, Hamburg, Germany; 4Hämatologisch – Onkologische Gemeinschaftspraxis, Nordhorn, Germany; 5Fachinternistische Gemeinschaftspraxis und Therapiezentrum, Witten, Germany; 6Onkologische Praxis, Hildesheim, Germany; 7Clinical Epidemiology and Health Economics, iOMEDICO, 8Statistics, iOMEDICO, Freiburg, Germany Purpose: Several randomized trials investigating the preferable first-line combination chemotherapy regimen for metastatic colorectal cancer have shown inconsistent findings. Because a substantial number of patients are still being treated with "chemo-only" first-line therapies without targeted agents, we compared overall survival (OS) of patients treated in routine practice with oxaliplatin–fluoropyrimidine and irinotecan–fluoropyrimidine. Patients and methods: Using the database of the Tumor Registry Colorectal Cancer, we identified 605 patients with metastatic colorectal cancer who received first-line fluoropyrimidine combination chemotherapy with either oxaliplatin (n=430) or irinotecan (n=175). The Tumor Registry Colorectal Cancer is a cohort study that prospectively documents treatment of colorectal cancer by office-based medical oncologists in Germany and has recruited over 5,000 patients. OS was estimated using the Kaplan–Meier method, and a multivariate Cox proportional hazard model was used to adjust for potentially confounding variables. Results: Median OS was 26.8 (95% confidence interval [CI] 22.4–31.9) months with an oxaliplatin–fluoropyrimidine combination and 18.3 (95% CI 15.1–23.2) months with irinotecan–fluoropyrimidine first-line "chemo-only" therapy. Median progression-free survival was 9.0 (8.1–10.2) and 7.9 (7.2–10.2) months, respectively. The difference in OS was confirmed if analysis was restricted to patients with synchronous metastases (no prior treatment). Among other variables, proportion of patients receiving any second-line therapy did not differ between groups. Oxaliplatin-based first-line therapy was associated with improved OS in multivariate analysis adjusted for potentially confounding variables (hazard ratio 0.678, 95% CI 0.510–0.901, P=0.007). Conclusion: In clinical routine practice, first-line treatment with oxaliplatin–fluoropyrimidine combination chemotherapy compared to irinotecan–fluoropyrimidine combination is associated with improved survival in patients with metastatic colorectal cancer, independent of all examined potentially confounding factors. Keywords: colorectal neoplasms, epidemiology, irinotecan, oxaliplatin, cohort studies, treatment outcome