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J Oncol Pract. 2008 May; 4(3): 114–115.
PMCID: PMC2794003

Undertreatment of Cancer Patients With Chemotherapy Is a Global Concern

Gary H. Lyman, MD, MPH

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Gary H. Lyman, MD, MPH

The efficacy of cancer chemotherapy is generally established on the basis of randomized controlled clinical trials evaluating a particular drug or combination using a specific dose and schedule. In adult patients with cancer, drug dosing has traditionally been based on a patient's estimated body-surface area (BSA), although there are little data supporting such a strategy. Despite continuing controversy concerning the value of dose escalation and intensification schedules, there exists compelling preclinical and clinical evidence indicating that reductions in standard dose intensity may compromise disease-free and overall survival in the curative setting.14 In practice, however, the delivery of full standard dose intensity is often not achieved for a variety of reasons including fear of excessive toxicity in elderly and obese patients.5,6

Cancer is largely a disease of aging, and the treatment of cancer in elderly patients should be cognizant of both limited bone marrow reserves and any associated comorbidity.7 With modern supportive care, however, it has been demonstrated that most elderly patients with cancer can both tolerate and benefit from standard chemotherapy regimens.710 Likewise, concerns about overdosing the obese patient with cancer based on the use of actual body weight are largely unfounded.5,1113 In fact, an obese patient with cancer often experiences less toxicity while deriving less benefit from such undertreatment, perhaps explaining the poorer outcomes often observed in such patients.11,14 Recent pharmacokinetic studies have clearly demonstrated that actual rather than ideal body weight should be used in dose calculations.15

Nevertheless, recent investigations, including the study from Australia reported in this issue of the Journal of Oncology Practice, confirm that many oncologists continue to either use “ideal” rather than actual body weight to calculate BSA or cap the BSA at 2.0 m2, resulting in a systematic underdosing of chemotherapy among overweight and obese patients.16 A large proportion of practicing oncologists and trainees in Australia responded to a survey soliciting their approach to dosing and dose reduction among the fit, the elderly, the obese, and the thin patient with cancer. While the majority stated that they dose based on actual body weight, half of all respondents indicated that they cap at a BSA 2.0 m2 when treating the obese patient with cancer. The majority of the remaining respondents dose based on ideal body weight, leaving only 6% who dose on the basis of actual weight. Only one fourth of oncologists indicated that they rarely dose reduce in this setting while another fourth do so routinely and half reduce in some cases. The investigators in the current study did not survey chemotherapy dosing in actual practice. However, the responses obtained are consistent with those found among oncology practices in the United States and elsewhere, demonstrating considerable variation in chemotherapy dosing of the elderly and the obese.5,8,16

Unfortunately, the problem identified here may be but the tip of the iceberg as it does not address those patients with limited access to oncology care, those who may not see or are not treated by an oncologist, and those who do not comply with treatment. Some authors have argued that chemotherapy dose intensity delivered in the curative cancer setting should be considered a quality-of-care measure.1,17 There does appear to be sufficient uncertainty on the part of oncologists on how best to dose elderly and obese patients with cancer that the American Society of Clinical Oncology might consider either a policy statement or the development of a clinical practice guideline providing appropriate recommendations for chemotherapy dosing based on a comprehensive systematic review of the available evidence. While more research is clearly needed in this important area, it is essential that the science that we do have is applied appropriately and effectively in the optimal treatment of patients with cancer.

References

1. Lyman GH: Chemotherapy dose intensity and quality cancer care. Oncology 20:16-25, 2006. (suppl 9) [PubMed]
2. Bonneterre J, Roche H, Kerbrat P, et al: Epirubicin increases long-term survival in adjuvant chemotherapy of patients with poor-prognosis, node-positive, early breast cancer: 10-year follow-up results of the French Adjuvant Study Group 05 randomized trial. J Clin Oncol 20 23:2686-2693, 2005 [PubMed]
3. Budman DR, Berry DA, Cirrincione CT, et al: Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer: The Cancer and Leukemia Group B. J Natl Cancer Inst 90:1205-1211, 1998. [PubMed]
4. Lepage E, Gisselbrecht C, Haioun C, et al: Prognostic significance of received relative dose intensity in non-Hodgkin's lymphoma patients: Application to LNH-87 protocol—The GELA (Groupe d'Etude des Lymphomes de l'Adulte). Ann Oncol 4:651-656, 1993. [PubMed]
5. Lyman GH, Dale DC, Crawford J: Incidence and predictors of low dose-intensity in adjuvant breast cancer chemotherapy: A nationwide study of community practices. J Clin Oncol 21:4524-4531, 2003. [PubMed]
6. Lyman GH, Dale DC, Friedberg J, et al: Incidence and predictors of low chemotherapy dose-intensity in aggressive non-Hodgkin's lymphoma: A nationwide study. J Clin Oncol 22:4302-4311, 2004. [PubMed]
7. Balducci L, Hardy CL, Lyman GH: Hemopoiesis and aging. Cancer Treat Res 124:109-134, 2005. [PubMed]
8. Shayne M, Culakova E, Poniewierski MS, et al: Dose intensity and hematologic toxicity in older cancer patients receiving systemic chemotherapy. Cancer 110:1611-1620, 2007. [PubMed]
9. Smith TJ, Khatcheressian J, Lyman GH, et al: 2006 update of recommendations for the use of white blood cell growth factors: An evidence-based clinical practice guideline. J Clin Oncol 24:3187-3205, 2006. [PubMed]
10. Kuderer NM, Dale DC, Crawford J, et al: Impact of primary prophylaxis with granulocyte colony-stimulating factor on febrile neutropenia and mortality in adult cancer patients receiving chemotherapy: A systematic review. J Clin Oncol 25:3158-3167, 2007. [PubMed]
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13. Griggs JJ, Sorbero ME, Lyman GH: Undertreatment of obese women receiving breast cancer chemotherapy. Arch Intern Med 165:1267-1273, 2005. [PubMed]
14. Colleoni M, Li S, Gelber RD, et al: Relation between chemotherapy dose, oestrogen receptor expression, and body-mass index. Lancet 366:1108-1110, 2005. [PubMed]
15. Sparreboom A, Wolff AC, Mathijssen RH, et al: Evaluation of alternate size descriptors for dose calculation of anticancer drugs in the obese. J Clin Oncol 25:4707-4713, 2007. [PubMed]
16. Field KM, Kosmider S, Jefford M, et al: Chemotherapy dosing strategies in the obese, elderly, and thin patients: Results of a nationwide survey. J Oncol Pract 4:111-116, 2008 [PMC free article] [PubMed]
17. Malin JL, Schneider EC, Epstein AM, et al: Results of the National Initiative for Cancer Care Quality: How can we improve the quality of cancer care in the United States? J Clin Oncol 24:626-634, 2006. [PubMed]

Articles from Journal of Oncology Practice are provided here courtesy of American Society of Clinical Oncology