Oncologic effects of chemotherapy dose capping in overweight and obese ovarian cancer patients

Abstract

<h3>Objectives:</h3> Chemotherapy dose capping in overweight and obese advanced ovarian cancer patients remains controversial in regard to its effect on oncologic outcomes and toxicity. <h3>Methods:</h3> Women with stage III or IV ovarian cancer receiving carboplatin and paclitaxel as primary therapy in combination with surgical resection between 1/2007-12/2016 were included in this retrospective study evaluating the interaction between body mass index (BMI) and chemotherapy dose capping on progression free survival (PFS) and toxicity. A calculated carboplatin dose based on the planned AUC and actual body weight (ABW) at the time of the first chemotherapy cycle following debulking surgery was compared to the dose received at this time based on the electronic medical record. A 5% or greater difference in treatment plan dosing received compared to actual weight-based dose was considered clinically significant. <h3>Results:</h3> 263 ovarian cancer patients were included in analysis (233 serous, 7 endometrioid, 14 clear cell, 8 carcinosarcoma, 1 NOS). Median age was 64 years (35-86). 62 (23.6%) received neoadjuvant chemotherapy prior to debulking surgery and 236 (88.2%) of all patients had an optimal cytoreductive surgery of <1cm. Median BMI was 25.1 (range 18.1-54.4). BMI cohorts included BMI <25 (128, 48.7%), BMI 25 to <30 (71, 27%), BMI ≥30. The calculated ABW carboplatin dose was at least 5% more than dose received in 38% of the total population. The rate of underdosing increased as BMI increased (8.6% BMI <25, 63.3% BMI 25 to <30, 68.7% BMI ≥30). There was no difference in PFS detected for patients with BMI <25 compared to BMI 25 or greater (HR 0.92 [CI 0.7-1.2], p=0.576). In patients with BMI of 25 or greater there was a trend toward PFS benefit when actual body weight was used for carboplatin dosing compared to modified adjusted body weight calculation (HR 0.7 [95% CI 0.47-1.04], p=0.078, Figure 1). Importantly, Grade 3 or 4 toxicity of any type did not appear to be increased in patients with BMI ≥25 receiving ABW carboplatin dosing compared to those with BMI ≥25 receiving modified dosing by adjusted body weight (Grade 3–4 toxicity 47.2% IBW dose v 30.4% ABW dose, p=0.068). Grade 3–4 toxicity rate in patient with BMI <25 was 45.3%. <h3>Conclusions:</h3> Carboplatin dose modification using adjusted body weight over a BMI of 25 may have a negative effect on PFS in ovarian cancer patients receiving primary therapy. Toxicity does not appear to be increased in this population when actual body weight is used for carboplatin dosing.