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Practicing physicians make multiple difficult treatment decisions daily. Several influences may affect choice of therapy, including consensus recommendations of the practice, ASCO or National Comprehensive Cancer Network guidelines, medical insurance coverage, geographic location of the practice, data from recently published or presented clinical trials, and familiarity with chemotherapeutic or biologic agent. Given the US Food and Drug Administration (FDA) approval of seven therapeutic agents in metastatic colorectal cancer, various treatment combinations may be considered. Practice patterns vary significantly within individual practices and may be more pronounced when comparing community versus academic settings.
Zafar et al1 have approached capturing community practice patterns in the population of patients with metastatic colorectal cancer, a challenging subject on which, to our knowledge, few data have been published. The objective of this study was to analyze longitudinal patterns of chemotherapy use and how recently published or presented scientific data translate into the real world of community practice. A retrospective medical record review of patients with metastatic colorectal cancer at the Duke University Medical Center (Durham, NC) and nine Duke University–affiliated community oncology practices was completed, inclusive of patients diagnosed between June 2003 and June 2006. All patients were treated with either fluorouracil (FU) -based chemotherapy with oxaliplatin (FOLFOX) or irinotecan (FOLFIRI). Patients participating in clinical trials were excluded. Of the 400 patients initially eligible, only 110 patients (28%) were included for the purpose of the analysis. Zafar et al noted that the majority of physicians chose oxaliplatin-based regimens for first-line therapy and irinotecan-based treatment for subsequent lines of therapy. Approximately two thirds of the medical records reviewed included no documentation to support the treatment decisions made. The authors suggested that age bias was present, because the majority of patients were younger than age 70 years. The authors encouraged prospective studies to identify physician intent in chemotherapy treatment.
Given the frequency of colorectal cancer in the United States, the number of recently approved therapeutics, and the concerns of pharmacoeconomics, practice patterns will continue to evolve as major discussion points. The objectives of such practice pattern studies must be clearly defined and critical to the primary study aim. In the study by Zafar et al,1 despite the stated aims of assessing longitudinal management representative of community practice, regimens other than FOLFOX and FOLFIRI were excluded, including irinotecan, bolus FU, and leucovorin (LV; IFL) at a time when this regimen was commonly used. A recent community-based practice pattern study demonstrated that one half of patients received a regimen other than FOLFOX, FOLFIRI, and IFL.2
Defining lines of therapy for metastatic colorectal cancer is also difficult because of variability in practice patterns. Reasons for changing therapy on the basis of clinical or radiographic progression, deferred treatment, rising carcinoembryonic antigen levels, or toxicity were not well documented. Does restarting oxaliplatin after progression while a patient is receiving maintenance FU/LV or on a prolonged treatment break constitute a new line of therapy? Given that 87% of patients in the study by Zafar et al1 received first-line oxaliplatin-based therapy, it is likely patients developed the dose limiting toxicity of peripheral neuropathy, which emphasizes the importance of transparency in documentation, because oxaliplatin may be reconsidered for future treatment if discontinued as a result of toxicity rather than progression of disease. Future studies investigating practice patterns should provide greater insight into the decisions physicians make.
From the data derived, the analysis by Zafar et al1 also confirms the tendency of physicians to make treatment choices on the basis of familiarity with therapy. As mirrored in practices across the country, oxaliplatin was preferentially chosen for first-line therapy on the basis of the superiority of FOLFOX versus IFL (NCCTG [North Central Cancer Treatment Group] 9741 trial, which did not include bevacizumab).3 After FDA approval of oxaliplatin, the FOLFOX regimen was widely utilized. Yet our European colleagues completed two phase III trials of FOLFIRI and FOLFOX as first-line therapy and noted equivalent response and overall survival and excellent tolerance of therapy.4,5 The impact of familiarity with drug on preferentially accepted use is additionally exemplified by the fact that the combination of FOLFOX and bevacizumab continues to be the most widely accepted first-line regimen among practicing physicians. Bevacizumab was originally approved by the FDA in combination with irinotecan. Hence, familiarity with the drug of interest appears to have precedence in practice patterns over recent evidence-based literature, as exemplified in the observational analysis by Zafar et al. The combination of FOLFIRI and bevacizumab continues to be underutilized in the United States as first-line therapy and should be considered in first-line therapy for any patient who is receiving palliative therapy, given its relatively few toxicities.6
Zafar et al1 suggested the existence of age bias because only 14% of patients were age 70 years or older. Yet the median age and percentage of patients age 70 years or older among those originally screened is unknown. Age bias has been reported in earlier studies but is neither supported nor refuted in the data presented here. A recent pooled analysis suggested that elderly patients age 70 years or older do not derive benefit from adjuvant FU-based therapies, contradicting prior studies suggesting equivalent benefit in elderly patients.7,8 Stratifying patients on the basis of comorbidities and functional status (ie, assessing biologic age in lieu of chronologic age) is required to define optimal chemotherapy utilization.
Whether the findings of the observation analysis by Zafar et al1 truly reflect the practice patterns in the community is difficult to ascertain, because the nine community practices are affiliated with Duke University, and this may have affected their current practice patterns. Although this small observational analysis was limited in its interpretation of practice patterns generalizable to the community setting, it emphasizes the importance and value of observational analyses and databases in improving quality measures for any practicing physician.
Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a “U” are those for which no compensation was received; those relationships marked with a “C” were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.
Employment or Leadership Position: None Consultant or Advisory Role: None Stock Ownership: None Honoraria: Cathy Eng, Bristol-Myers Squibb, Pfizer, Roche Research Funding: Cathy Eng, Amgen, sanofi-aventis, Bristol-Myers Squibb, Novartis, Genentech Expert Testimony: None Other Remuneration: Scott Kopetz, Roche, sanofi-aventis, Genentech