Clinical trials confirm that therapy with agents including 5-FU, oxaliplatin, capecitabine, and oxaliplatin is associated with improved survival of patients with stage III and IV mCRC [3
]. Importantly, compared with younger patients in the setting of clinical trials, this population-based retrospective cohort analysis of elderly patients in community settings revealed comparable benefits in overall survival and complications requiring medical resource utilization in response to these treatments [44
The finding that patients treated with CAP were older and had a higher comorbidity burden compared with the three other treatment groups may reflect a belief among physicians that elderly patients are frailer and less able to tolerate aggressive or more toxic treatments. A recent review of the medical records of patients aged 65 or older diagnosed with stage III colon cancer between 2003 and 2006 revealed that 61 % received a regimen containing oxaliplatin, 54 % were treated with FOLFOX, 19 % received 5-FU/LV, and 12 % were administered with capecitabine monotherapy. Among those not treated with oxaliplatin, the primary reason was comorbid health conditions with age cited as a reason for not administering oxaliplatin for 19 % of patients [27
Patient characteristics such as age, gender, race, and comorbidity burden appear to be important factors in prescribing chemotherapy treatment, but after adjusting for these factors, there were no significant differences in OS between the CAP-based and 5-FU/LV-based regimens. This is an encouraging finding for all patients diagnosed with advanced stage CRC, suggesting that currently available and recommended systemic therapies are equally effective for patients with diverse clinical and demographic characteristics.
Our study observed that complications requiring medical resource utilization were less frequent for CAP ± oxaliplatin regimens while achieving an equivalent survival benefit compared with 5-FU/LV ± oxaliplatin regimens. This confirms similar observations from randomized clinical trials that CAP monotherapy is associated with a lower rate of adverse events and reduced medical resource utilization [8
]. Randomized clinical trials report comparative safety profiles for CAP ± oxaliplatin regimens vs. 5-FU/LV ± oxaliplatin with more grade 3 or 4 neutropenia and neutropenic fever associated with FOLFOX and more grade 3 hand–foot syndrome and grade 3 or 4 diarrhea associated with CAPOX [11
]. However, the incidence of medically significant diarrhea, i.e., requiring medical resources, was reduced in patients receiving CAPOX vs. FOLFOX in our study. Dose selection was at the discretion of the physician and dosing information could not be determined retrospectively from available data within the claims dataset. Regional differences in tolerance to FP, both CAP and 5-FU/LV, have been reported with US patients more likely to experience grade 3 or 4 FP-related toxicities compared with patients from other parts of world, particularly Asia [48
]. Physicians may have elected to use doses (lower) and/or treatment schedules other than those tested in clinical trials that may have impacted the safety profile of the regimen. These findings confirm that capecitabine-based treatments can be delivered to elderly patients under the conditions of routine medical care with outcomes similar to those achieved in overall clinical trial populations for patients ≥65 years of age.
Initiation of chemotherapy for all four treatment regimens was longer (mean time, 74 to 81 days) than the typical 30 days that would be expected. Prior research has shown that not only do treatment rates decline dramatically with increasing age [51
], but older age is associated with delayed chemotherapy initiation [52
] and lower rates of chemotherapy completion [53
]. These age disparities in treatment patterns are associated with higher mortality [52
] and our results provide further support that demographic factors such as age should not discourage the use of guideline-recommended therapies.
Study Strengths and Limitations
This study has several strengths, including the large sample size from a population-based registry with a wide geographic representation of patients with CRC in the USA. The SEER–Medicare dataset provides inpatient and outpatient data, comprehensive information about covered services, all claims regardless of residence or care out of area, and longitudinal data with claims for services from the time a person is eligible for Medicare until the date of death. However, use of the SEER–Medicare data for this type of analysis has some limitations, particularly for determining accurate utilization rates of oral chemotherapeutic agents such as capecitabine. A recent comparison of Medicare claims with the National Cancer Institute's Patterns of Care studies showed that among patients with various cancers receiving chemotherapy (including stage II/III CRC), Medicare claims data more accurately identified agents that were intravenously administered [54
In addition, the SEER–Medicare database does not provide data on performance status or lifestyle factors, such as smoking. These factors could have affected the treatment patterns we observed or clinicians' initial decisions to treat these patients. Furthermore, treatment patterns for the older population with Medicare coverage may be different from those used for younger patients and, therefore, the results might have limited applicability to younger populations in real-world settings. This analysis also does not yield information about patients enrolled in HMOs since these data are not collected by Medicare. It is conceivable that treatment patterns, prognosis, and complications may differ between HMO and Medicare enrollees. Previous studies found that Medicare HMO enrollees with colon cancer had better OS compared with fee-for-service (FFS) plan members [55
]. These mortality differences might have been due to higher use of screening and preventive services for HMO patients or the possibility that HMO enrollees tend to be healthier than FFS enrollees.