Outcomes of irinotecan-based chemotherapy regimens in elderly Medicare patients with metastatic colorectal cancer.

Background: Several population-based studies have confirmed the benefits of adjuvant chemotherapy with 5-fluorouracil/leucovorin for treatment of colorectal cancer. Few population-based studies have evaluated other chemotherapies that are now available for colorectal cancer management.

Objective: This study primarily sought to evaluate the survival benefit of first-line irinotecan use in a group of Medicare patients with stage IV (metastatic) colorectal cancer.

Methods: Data on chemotherapy users with a diagnosis of colorectal cancer reported between 1998 and 2002 were obtained from the Surveillance Epidemiology and End Results (SEER)-Medicare database. Irinotecan, marketed in 1997, was one of the newer chemotherapy agents in the available data. Chemotherapy episodes, defined as periods of continuous chemotherapy treatment with no gaps >90 days between successive claims, were identified. The first chemotherapy episode after diagnosis was used to identify lines of treatment: patients may have initiated irinotecan therapy within 2 months (first-line), used irinotecan later in the first episode (second-line), or not used irinotecan at all. Descriptive statistics were generated and a multivariable Cox proportional hazards model was used to determine the survival benefit of irinotecan. Secondary analyses explored the survival benefit in specific patient subgroups. The impact of irinotecan use on health care utilization also was assessed.

Results: Of 3327 chemotherapy users (mean/median age, 75 years), 842 (25.3%) initiated chemotherapy using irinotecan. No overall survival benefit for irinotecan was observed in the primary analysis comparing irinotecan initiators with all other chemotherapy users (including those who used irinotecan subsequently). Covariates that were negatively associated with survival included older age, presence of >1 comorbidity, a high tumor grade, lymph node involvement, and a primary tumor site in the colon. Surgery was positively associated with a lower hazard of death. In subgroup analyses that excluded subsequent irinotecan users, a survival benefit for irinotecan was observed but diminished over time. Irinotecan users had higher rates of hospitalizations possibly due to chemotherapy-related adverse effects. This retrospective claims study had limitations such as a lack of information on patient performance status, dosing, and the types of regimens used; hence, certain assumptions had to be made and selection bias may have been involved.

Conclusions: The definitive survival advantage of irinotecan observed in clinical trials was not reproducible in this population of elderly Medicare patients. The results emphasize the need for expansion of trials to include a more diverse patient group as well as continued evaluation of more recent chemotherapies in real-world settings.