The American Society of Clinical Oncology (ASCO) published clinical practice guidelines on the appropriate chemotherapy dosing for obese adult patients with cancer in 2012.51 These guidelines were not specific to ovarian cancer, however the guidelines noted that a majority of studies identified in the systematic review for the guidelines involved breast, ovarian, colon and lung cancers. The ASCO guidelines recommend that full weight-based cytotoxic chemotherapy doses be used to treat obese patients with cancer, particularly when the goal of treatment is cure.(ASCO: http://jco.ascopubs.org/cgi/doi/10.1200/JCO.2011.39.9436)
No studies were identified which specifically compared different doses of chemotherapy among obese patients for survival outcomes.
Nine studies were identified which included obese patient populations and compared outcomes by BMI or by obesity. In most of the studies, chemotherapy dosing was based on actual body weight, whereas in some studies the formula used did not include body weight or body surface areas (BSA). Six of the studies examined the impact of BMI on outcomes including survival and adverse events.64-69 Three of the studies reported on adverse events and BMI only.71, 85, 86
Hourdequin et al (2013) published a systematic review and meta-analysis of studies comparing toxic effect and survival outcomes between obese and normal weight cancer patients. Patients in the studies were from various tumour groups. Both obese and normal weight patients received chemotherapy dosed using actual body weight, without dose reductions. The authors concluded that obese patients receiving chemotherapy based on actual body weight experienced similar or lower rates of toxic effects as normal weight patients, and survival outcomes do not differ.87
An additional study published in 2014 was also identified. Au-Yeung et al (2014) published a retrospective study from the Australian Ovarian Cancer Study (AOCS) to evaluate the relationship between BMI, dose intensity of chemotherapy received, overall survival and progression-free survival. Doses were calculated based on standard treatment regimen.70
Survival
No significant differences in overall, progression-free or disease-free survival were reported between obese and non-obese patients in most of the studies. One study SCOTROC I, (Barrett et al, 2008) did not find a link between obesity and poorer prognosis, with the authors noting this finding was due to more accurate dose calculations in that study.65 The authors recommended accurate measurement of GFR and chemotherapy doses based on actual body weight rather than ideal body weight.
Au-Yeung et al (2014) reported no significant association between BMI groups and overall or progression-free survival. Patients who received less than 85% RDI for carboplatin had significantly worse progression-free survival (univariate analysis: median PFS 11 vs. 15mths; p=0.04). In multivariate analysis, the difference in progression-free survival for RDI of carboplatin trended in the same direction but no longer reached statistical significance (p=0.06).\
Dosing
The majority of studies reported similar numbers of lines, courses, number of platinum-based regimens of chemotherapy between obese and non-obese patients. One study (Hanna et al 2013) determined BSA greater than 2m2 and BMI >30 kg/m2 to be predictors of reduced planned relative dose intensity (RDI) <85% and reduced delivered RDI <85%.68
Wright et al (2008) reported that over the entire treatment course, the average dose of carboplatin received during treatment did not differ across BMI strata.64
Data from the SCOTROC I trial, showed no statistically significant differences overall between the two arms for dose intensity or cumulative dose. In the current study of 1067 patients who received taxane treatment and had recorded BMI, there was neither a statistically significant difference in taxane dose intensity (p=0.120) nor carboplatin dose intensity (p=0.578) between the BMI categories.65 There was also no statistically significant difference between total intended taxane dose (p=0.217) or total intended carboplatin dose (p=0.722) between BMI categories. Based on the findings of no significant differences in survival between BMI categories from this study, in which chemotherapy dose was based on measured GFR, the authors suggested accurate measurement of GFR before commencing chemotherapy and chemotherapy doses based on actual body weight.65
In the study by Suh et al. (2012), there were no significant differences across BMI categories for the number of lines of chemotherapy used, the number of courses of chemotherapy or the number of courses before recurrence.67 The level of neutropenia and platinum sensitivity rate were also similar in BMI groups.
Au-Yeung et al (2014) reported that obese patients were more likely to receive RDI <85% for carboplatin compared to non-obese patients (p<0.001). The RDI comparison for paclitaxel was not significantly different between BMI groups (p=0.76). For the average RDI for both carboplatin and paclitaxel, significantly more obese patients received an average RDI <85% (p=0.02).
Adverse events
Adverse events reported, and any differences between BMI groups, varied between studies. In the study by Wright et al, in which the carboplatin dose calculation did not adjust for body weight, obese women were reported to experience less treatment-related toxicity compared with normal weight subjects.64 The authors suggested that as obese women were less likely to experience treatment-related toxicity, these women received a lower effective dose of carboplatin and that body weight should be taken into consideration when calculating carboplatin dose.64
Matthews et al (2009) reported similar rates of neutropenia for obese and non-obese patients (52% and 46%, p=0.39).66
In the Japanese study by Sendo et al (2005) a multivariate analysis demonstrated that the incidence of hypersensitivity reactions to paclitaxel was significantly higher in obese patients (BMI >25)(OR 8.47, 95% CI 1.48-48.57, p=0.017).86
Laskey et al (2012) reported that BMI <30 and BSA <2.0 m2 were significant predictors of severe neutropenia in women with stage III and IV epithelial ovarian cancer by univariate analysis (p=<0.01 and p=0.03).71 Multivariate analysis indicated a trend to an association between severe neutropenia and BMI <30 (HR 1.60, p=0.06).