Obesity and chemotherapy administration: between empiric and mathematic method review

Abstract

Introduction: Obesity is a major risk factor for chronic disease and cancer development. Therapeutic management of obese patients with cancer is a real challenge for physician because of the alteration of antineoplastic pharmacokinetics parameters in this population. In routine clinical practices, chemotherapy doses in obese patients are arbitrarily capped or adjusted to an ideal weight to minimize excessive toxicities. Material and methods: The main goal of this review is to describe the current state of knowledge concerning the correlation between the adjustment of BSA (capping or ideal weight) and the rates of global toxicities and survival outcomes in obese patients under chemotherapy in different types of cancer. We searched in the Medline database (via PubMed) in order to identify all publications of literature reviews whose subject chemotherapy dosing in obese population. Results: Only a single study was pointing toward increased of global toxicities of full weight dosing. Furthermore, some studies suggests that the practice of limiting doses in overweight and obese patients may negatively influence the quality of care and outcomes in a constantly increasing population. Conclusion: This review highlights the lack of prospective studies focusing on chemotherapy methods of administration in obese patients. At this time, there is no prospective study comparing capping and full weight dose chemotherapy administration in obese patient population.

Impact of Obesity on Quality of Life, Psychological Distress, and Coping on Patients with Colon Cancer

“…Various retrospective studies, pos hoc analyses of clinical trials, and metanalyses have compared survival and chemotherapy toxicity between obese and non-obese patients with cancer, primarily breast and colon cancers, yielding disparate data [14,[42][43][44][45][46]. In a systematic review, Carroll JP et al examined the impact of obesity on adjuvant treatment of breast cancer.…”

Body surface area capping may not improve cytotoxic drugs tolerance

“…Furthermore, capping did not induce more dose reduction in over 2m 2 BSA patients. Bouleftour et al review highlighted the lack of prospective studies focusing on chemotherapy methods of administration in obese patients 22 . Indeed, based on the results of this work, prospective clinical trials are crucial in order to bring scientific proof to this empirical practice.…”

Antineoplastic dosing in overweight and obese cancer patients: an Associazione Italiana Oncologia Medica (AIOM)/Associazione Medici Diabetologi (AMD)/Società Italiana Endocrinologia (SIE)/Società Italiana Farmacologia (SIF) multidisciplinary consensus position paper

“…8 Several retrospective studies in early-stage cancer patients reported that adjuvant chemotherapy dosage was often reduced in obese patients, with a subsequent negative impact on the clinical outcome. 7,9,62,63 Stocker et al, 64 in an exploratory analysis of a PETACC 3 study, showed that dose reduction negatively affected relapse-free survival (RFS) [hazard ratio (HR): 0.48, 95% confidence interval (CI), 0.27-0.85; P ¼ 0.01] with a strong trend toward better OS (HR: 0.53, 95% CI, 0.28-1.01; P ¼ 0.052) in patients with BMI 30 kg/m 2 and BSA 2 m 2 receiving adjuvant chemotherapy for colon cancer. 9 Similarly, the CALGB study 8541 supports the use of full-dose chemotherapy compared with a reduced initial dose due to the improved failure-free survival in obese women (overall adjusted failure risk ratio of 0.73, 95% CI, 0.53-1.00).…”

“…7,9,62,63 Stocker et al, 64 in an exploratory analysis of a PETACC 3 study, showed that dose reduction negatively affected relapse-free survival (RFS) [hazard ratio (HR): 0.48, 95% confidence interval (CI), 0.27-0.85; P ¼ 0.01] with a strong trend toward better OS (HR: 0.53, 95% CI, 0.28-1.01; P ¼ 0.052) in patients with BMI 30 kg/m 2 and BSA 2 m 2 receiving adjuvant chemotherapy for colon cancer. 9 Similarly, the CALGB study 8541 supports the use of full-dose chemotherapy compared with a reduced initial dose due to the improved failure-free survival in obese women (overall adjusted failure risk ratio of 0.73, 95% CI, 0.53-1.00). 63 The likelihood of receiving a first-cycle dose reduction (<90% of the expected dose) increased in step with the obesity grade, being 11%, 20% and 37% in overweight, obese and severely obese patients, respectively, in a retrospective cohort study of 9672 breast cancer women treated with doxorubicin hydrochloride and cyclophosphamide.…”

“…Anticancer agent doses are personalized according to the patient's weight or body surface area (BSA). 9 Less common methods for determining dosing for adult cancer patients include 'flat-fixed' dosing 10 and 'dose banding' 11 which help to avoid potential calculation errors. It is well known that anthropometric changes in obese individuals, as regards body proportions of water, fat and muscle mass, are accompanied by variations in district-specific blood flow, alterations of liver and renal functions and chronic, lowgrade inflammatory state.…”