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First Published Online January 6, 2009
The Oncologist, Vol. 14, No. 1, 106-107, January 2009; doi:10.1634/theoncologist.2008-0242
© 2009 AlphaMed Press

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Letters to the Editor

In Reply

Trevor McKibbina, Jim M. Koellerb

aCollege of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA; bUniversity of Texas Health Science Center at San Antonio and College of Pharmacy, University of Texas at Austin, Austin, Texas

Correspondence: Trevor McKibbin, Pharm.D., M.S., College of Pharmacy, University of Tennessee Health Science Center, 930 Madison, Suite 890, Memphis, Tennessee, USA. Telephone: 901-448-7632; Fax: 901-448-5419; e-mail: tmckibbi{at}utmem.edu

Received November 4, 2008; accepted for publication November 24, 2008; first published online in THE ONCOLOGIST Express on January 6, 2009.

Disclosures

Trevor McKibbin: Consultant/advisory role: Genentech; Jim M. Koeller: Consultant/advisory role: Bristol-Myers Squibb, Sanofi Aventis, AstraZeneca, Genentech, Pharmion; Speaker: Pfizer, MGI Pharma, Lilly, Abraxis

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by independent peer reviewers.

We thank Dr. Moore et al. for their comment on our study [1]. The primary objective of our study was to identify which chemotherapy regimens were being used in patients with advanced colorectal cancer >65 years of age compared with younger patients. Our results identified significant differences in these age groups, while controlling for confounding variables.

Dr. Moore et al. raise the question of how chemotherapy dosing may impact the interpretation of our results. We thank them for the opportunity to address this important issue. We analyzed initial doses received in the most frequently used first-line combination chemotherapy regimens. These included IFL, FOLFIRI, FOLFOX, and CapeOx. There are multiple iterations of regimens (e.g, FOLFOX4, FOLFOX6, and FOLFOX7) and combining the treatments into these broad categories allows this analysis to detect differences in the use of less dose-intensive versions of the regimens [2–4]. The starting doses (based on mg/m2) of oxaliplatin and irinotecan in these regimens were not significantly different across age groups (Table 1). In the practices in this evaluation, the elderly patients were less likely to receive irinotecan, oxaliplatin, and bevacizumab [1]. However, when initiated, comparable starting doses based on body surface area were used.


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  		Table 1. Doses by regimen and age group

 
Dr. Moore et al. state that our study implies a link between the practice patterns observed and the treating clinicians. Unless some unknown subterfuge was at play in these clinics, treatment received generally does link back to the treating clinician. One valid concern is the degree to which patient preferences may have impacted the treatments received. This is an important area of research that is beyond the scope of this study. Although often relying on post hoc subgroup analysis, the current clinical trial data suggest that older patients should receive the same therapy as younger patients [5–7]. The findings from our data indicate that these clinical trial data are not able to be fully translated into practice. Further research is needed to understand why. Patient preference and patient education may be important factors. Patient treatment decisions arise from a complex matrix of factors. In previous literature, age was not consistently a factor related to treatment preference [7–11]. Further investigations are required to understand which factors are impacting the treatments received by patients.

The word disparity was used because there were clear differences in treatments received initially and throughout the treatment course between younger and older patients. These differences were significant and may have impacted outcome. Previous trials have questioned the overall survival benefit of initial combination chemotherapy compared with a sequential approach [12, 13]. This study was an observation of treatments received, management of adverse events, and outcomes obtained, not a prospective clinical trial [1]. The overall survival data were appropriately discussed in the context of important limitations. In this investigation, the elderly were less likely to receive several of the readily available active therapies. This remained true throughout the treatment course. Whether an initial combination chemotherapy approach or a sequential approach was taken, the elderly were less likely to receive irinotecan, oxaliplatin, and bevacizumab.

The decision to measure survival from the initiation of therapy was made because this time point mimics the time point used in clinical trials, that is, time from randomization. The data presented in the commentary on a limited cohort of patients is intriguing, but the validity of the watch and wait approach described by Moore et al. requires further evaluation compared with initial combination therapy or sequential treatment approaches [14].

Lastly, at no point in our study are comments provided, or implications made regarding the appropriateness of the therapies observed. Overall, we observed treatment patterns that were markedly different between older patients and younger patients. These differences were present at the initiation of therapy and throughout the treatment course. Additional research is needed to identify the underlying reasons for these differences.


   REFERENCES
Top
 References
 

  1. McKibbin T, Frei CR, Greene RE et al. Disparities in the use of chemotherapy and monoclonal antibody therapy for elderly advanced colorectal cancer patients in the community oncology setting. The Oncologist 2008;13:876–885.[Abstract/Free Full Text]
  2. Tournigand C, André T, Achille E et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: A randomized GERCOR study. J Clin Oncol 2004;22:229–237.[Abstract/Free Full Text]
  3. Tournigand C, Cervantes A, Figer A et al. OPTIMOX1: A randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-go fashion in advanced colorectal cancer—a GERCOR study. J Clin Oncol 2006;24:394–400.[Abstract/Free Full Text]
  4. Colucci G, Gebbia V, Paoletti G et al. Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: A multicenter study of the Gruppo Oncologico Dell'Italia Meridionale. J Clin Oncol 2005;23:4866–4875.[Abstract/Free Full Text]
  5. Chau I, Norman AR, Cunningham D et al. Elderly patients with fluoropyrimidine and thymidylate synthase inhibitor-resistant advanced colorectal cancer derive similar benefit without excessive toxicity when treated with irinotecan monotherapy. Br J Cancer 2004;91:1453–1458.[CrossRef][Medline]
  6. Goldberg RM, Tabah-Fisch I, Bleiberg H et al. Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer. J Clin Oncol 2006;24:4085–4091.[Abstract/Free Full Text]
  7. Donovan KA, Greene PG, Shuster JL et al. Treatment preferences in recurrent ovarian cancer. Gynecol Oncol 2002;86:200–211.[CrossRef][Medline]
  8. Extermann M, Albrand G, Chen H et al. Are older French patients as willing as older American patients to undertake chemotherapy? J Clin Oncol 2003;21:3214–3219.[Abstract/Free Full Text]
  9. Jansen SJ, Kievit J, Nooij MA et al. Patients' preferences for adjuvant chemotherapy in early-stage breast cancer: Is treatment worthwhile? Br J Cancer 2001;84:1577–1585.[CrossRef][Medline]
  10. Jansen SJ, Otten W, Stiggelbout AM. Review of determinants of patients' preferences for adjuvant therapy in cancer. J Clin Oncol 2004;22:3181–3190.[Abstract/Free Full Text]
  11. Newcomb PA, Carbone PP. Cancer treatment and age: Patient perspectives. J Natl Cancer Inst 1993;85:1580–1584.[Abstract/Free Full Text]
  12. Koopman M, Antonini NF, Douma J et al. Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): A phase III randomised controlled trial. Lancet 2007;370:135–142.[CrossRef][Medline]
  13. Seymour MT, Maughan TS, Ledermann JA et al. Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): A randomised controlled trial. Lancet 2007;370:143–152.[CrossRef][Medline]
  14. Expectancy or primary chemotherapy in patients with advanced asymptomatic colorectal cancer: A randomized trial. Nordic Gastrointestinal Tumor Adjuvant Therapy Group. J Clin Oncol 1992;10:904–911.[Abstract]




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