Appropriate Systemic Therapy Dosing for Obese Adult Patients With Cancer: ASCO Guideline Update.

PURPOSE: To provide recommendations for appropriate dosing of systemic antineoplastic agents in obese adults with cancer. METHODS: A systematic review of the literature collected evidence regarding dosing of chemotherapy, immunotherapy, and targeted therapies in obese adults with cancer. PubMed and the Cochrane Library were searched for randomized controlled trials, meta-analyses, or cohort studies published from November 1, 2010, through March 27, 2020. ASCO convened an Expert Panel to review the evidence and formulate recommendations. RESULTS: Sixty studies, primarily retrospective, were included in the review. Overall, the evidence supported previous findings that obese adult patients tolerate full, body-size-based dosing of chemotherapy as well as nonobese patients. Fewer studies have addressed the dosing of targeted therapies and immunotherapies in relation to safety and efficacy in obese patients. RECOMMENDATIONS: The Panel continues to recommend that full, weight-based cytotoxic chemotherapy doses be used to treat obese adults with cancer. New to this version of the guideline, the Panel also recommends that full, approved doses of immunotherapy and targeted therapies be offered to obese adults with cancer. In the event of toxicity, the consensus of the Panel is that dose modifications of systemic antineoplastic therapies should be handled similarly for obese and nonobese patients. Important areas for future research include the impact of sarcopenia and other measures of body composition on optimal antineoplastic dosing, and more customized dosing based on pharmacokinetic or pharmacogenetic factors.Additional information is available at www.asco.org/supportive-care-guidelines.

Adjuvant endocrine therapy initiation and persistence in a diverse sample of patients with breast cancer.

Adjuvant endocrine therapy for breast cancer reduces recurrence and improves survival rates. Many patients never start treatment or discontinue prematurely. A better understanding of factors associated with endocrine therapy initiation and persistence could inform practitioners how to support patients. We analyzed data from a longitudinal study of 2,268 women diagnosed with breast cancer and reported to the Metropolitan Detroit and Los Angeles SEER cancer registries in 2005-2007. Patients were surveyed approximately both 9 months and 4 years after diagnosis. At the 4-year mark, patients were asked if they had initiated endocrine therapy, terminated therapy, or were currently taking therapy (defined as persistence). Multivariable logistic regression models examined factors associated with initiation and persistence. Of the 743 patients eligible for endocrine therapy, 80 (10.8 %) never initiated therapy, 112 (15.1 %) started therapy but discontinued prematurely, and 551 (74.2 %) continued use at the second time point. Compared with whites, Latinas (OR 2.80, 95 % CI 1.08-7.23) and black women (OR 3.63, 95 % CI 1.22-10.78) were more likely to initiate therapy. Other factors associated with initiation included worry about recurrence (OR 3.54, 95 % CI 1.31-9.56) and inadequate information about side effects (OR 0.24, 95 % CI 0.10-0.55). Factors associated with persistence included two or more medications taken weekly (OR 4.19, 95 % CI 2.28-7.68) and increased age (OR 0.98, 95 % CI 0.95-0.99). Enhanced patient education about potential side effects and the effectiveness of adjuvant endocrine therapy in improving outcomes may improve initiation and persistence rates and optimize breast cancer survival.

The influence of non-clinical patient factors on medical oncologists' decisions to recommend breast cancer adjuvant chemotherapy.

The extent to which medical oncologists consider non-clinical patient factors when deciding to recommend adjuvant chemotherapy is unknown. Medical oncologists who treated a population-based sample of early stage breast cancer patients reported to the Los Angeles and Detroit Surveillance, Epidemiology, and End Results registries 2005-2007 were asked how strongly they consider a patient's ability to follow instructions, level of social support, and level of work support/flexibility in decisions to recommend adjuvant chemotherapy. Responses of 4 (Quite strongly) or 5 (Very strongly) on a five-point Likert scale defined strong consideration. Associations between oncologist/practice characteristics and strong consideration of each non-clinical factor were examined. 134 oncologists (66 %) reported strong consideration of one or more factor. Ability to follow instructions was strongly considered by 120 oncologists (59 %), social support by 78 (38 %), and work support/flexibility by 73 (36 %). Larger percent of practice devoted to breast cancer was associated with lower likelihood of strongly considering ability to follow instructions [odds ratio (OR) 0.98, 95 % confidence interval (CI) 0.97-0.99; P = 0.04]. Increased years in practice was associated with lower likelihood of strongly considering social support (OR 0.96, CI 0.93-0.99; P = 0.011), while non-white race (OR 2.1, CI 1.03-4.26; P = 0.041) and tumor board access (OR 2.04, CI 1.01-4.12; P = 0.048) were associated with higher likelihood. Non-white race was associated with strongly considering work support/flexibility (OR 2.44, CI 1.21-4.92; P = 0.013). Tumor board access (OR 2, CI 1.00-4.02; P = 0.051) was borderline significant. Non-clinical patient factors play a role in medical oncologist decision-making for breast cancer adjuvant chemotherapy recommendations.

Appropriate chemotherapy dosing for obese adult patients with cancer: American Society of Clinical Oncology clinical practice guideline.

PURPOSE: To provide recommendations for appropriate cytotoxic chemotherapy dosing for obese adult patients with cancer. METHODS: The American Society of Clinical Oncology convened a Panel of experts in medical and gynecologic oncology, clinical pharmacology, pharmacokinetics and pharmacogenetics, and biostatistics and a patient representative. MEDLINE searches identified studies published in English between 1996 and 2010, and a systematic review of the literature was conducted. A majority of studies involved breast, ovarian, colon, and lung cancers. This guideline does not address dosing for novel targeted agents. RESULTS: Practice pattern studies demonstrate that up to 40% of obese patients receive limited chemotherapy doses that are not based on actual body weight. Concerns about toxicity or overdosing in obese patients with cancer, based on the use of actual body weight, are unfounded. RECOMMENDATIONS: The Panel recommends that full weight-based cytotoxic chemotherapy doses be used to treat obese patients with cancer, particularly when the goal of treatment is cure. There is no evidence that short- or long-term toxicity is increased among obese patients receiving full weight-based doses. Most data indicate that myelosuppression is the same or less pronounced among the obese than the non-obese who are administered full weight-based doses. Clinicians should respond to all treatment-related toxicities in obese patients in the same ways they do for non-obese patients. The use of fixed-dose chemotherapy is rarely justified, but the Panel does recommend fixed dosing for a few select agents. The Panel recommends further research into the role of pharmacokinetics and pharmacogenetics to guide appropriate dosing of obese patients with cancer.