Muscle depletion and the prediction of chemotherapy toxicity

Abstract

SIMI 2013 During the past few decades, while the death rate for heart disease has declined steadily, cancer death rates have remained relatively constant [1]. Moreover, cancer is becoming a disease associated with aging, with patients aged 65 years and older having an 11-fold increase in cancer incidence and a 16-fold increase in cancer mortality when compared to individuals younger than 65 [2, 3]. The population of older adults is rapidly growing worldwide, and it is estimated that the number of people older than 65 will exceed 20 % by 2030 in the United States. Furthermore, aging is paralleled by an increase in comorbidities, which increases patients’ vulnerability [4]. This will progressively increase the need for cost-effective antineoplastic strategies for an increasing population of patients. Part of the limited efficacy of cancer treatments is related to chemotherapy toxicity [5–7]. Up to 30 % of patients treated with 5-fluorouracil (5-FU)/capecitabine experience dose-limiting toxicities including diarrhea, handfoot syndrome, mucositis and myelosuppression [8]. Toxicity frequently implies reduction or interruption of anticancer therapy and may lead to fatal complications, particularly in older persons [3, 9]. Besides its detrimental role in negatively affecting prognosis and survival of cancer patients, toxicity to chemotherapy negatively impacts on the financial burden of cancer, causing increase in both direct medical costs and indirect mortality costs [10] An American pilot study [11] evaluating the total costs of chemotherapy-induced toxicity in ovarian cancer patients in 2001 estimates that the cost for every single episode of neutropenia is USD $ 7,546. In a subsequent study from the same group [12], the cost per episode of febrile neutropenia in patients receiving inpatient care ranges between USD $ 12,150 and USD $ 21,601. Thus, the control of chemotherapy-induced toxicity has become a major healthcare issue, and systems or models for the prompt and effective identification of patients at risk are strongly required. The study of mutations in metabolic enzymes involved in drug metabolism represents an