Abstract P1-13-04: Higher rate of severe toxicities in obese patients receiving dose-dense chemotherapy according to unadjusted body mass index – Results of the prospectively randomized GAIN study
Authors: Furlanetto J , Eiermann W , Marmé F , Reimer T , Reinisch M , Schmatloch S , Stickeler E , Thomssen C , Untch M , Denkert C , von Minckwitz G , Nekljudova V , Loibl S , Möbus V 
Published: May 2016

Abstract
Background: In routine clinical practice chemotherapy (CT) doses are frequently capped at a body surface area (BSA) of 2.0 m2 or adjusted to an ideal weight (i.e. [body length in cm - 10%] + 40% [current weight-ideal weight]) for obese patients (BMI&gt;30 according to WHO) due to safety reasons. There are no data on CT dosing within intense dose-dense regimen for obese patients. Therefore, a retrospective analysis of the GAIN study population has been conducted.
Methods: Between August 2004 and July 2008 a total of 3023 patients were enrolled in the GAIN study, a randomized phase III adjuvant trial, comparing two types of dose-dense regimen. Patients were randomized to intense dose-dense ETC (Epirubicin 150 mg/m2, Paclitaxel 225 mg/m2, Cyclophosphamide 2500-2000 mg/m2, i.v. q15 for 3 cycles) or EC followed by T plus capecitabine (X) (EC-TX) (E 112.5 mg/m2 + C 600 mg/m2, i.v. q15 for 4 cycles followed by T 67.5 mg/m2 i.v. q8 for 10 weeks + X: 2000 mg/m2 p. o. day 1-14, q22 for 4 cycles). An adjustment of CT dose to an ideal weight for obese patients was implemented by a protocol amendment. Yet some patients received a dose adjustment by capping at 2.0 m2. We retrospectively evaluated a total of 543 patients with a BMI&gt;30. Data on BSA and dose adjustment were collected from case report forms. Toxicities were compared between patients who received CT according to an unadjusted or adjusted BSA using the 2-sided exact test of Fisher. Disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method and the log-rank test.
Results: Overall, 18.0% (n=543) of patients in the GAIN study were obese: 30.9% (n=168) of them received CT according to an unadjusted BSA. For the remainder BSA was adjusted to ideal weight or was capped at 2.0 m2 (69.1%; n=375). A total of 14.5% (n=24) of obese patients receiving full dose of chemotherapy vs 6.4% (n=24) of obese patients with an adjusted BSA experienced febrile neutropenia (p=0.005) and 9.6% (n=16) vs 2.9% (n=11) high grade thrombopenia (p=0.002). Overall, 16.7% (n=28) vs 10.1% (n=38) had a thromboembolic event (p=0.034), which was high grade in 12.5% (n=21) vs 6.4% (n=24), respectively (p=0.027) and 3.0% (n=5) vs 0.3% (n=1) experienced high grade hot flushes (p=0.012). The only significant differences in favor of the non-adjusted group were for dizziness (4.2% [n=7] vs 10.7% [n=40]; p=0.013), diarrhea (18.5% [n=31] vs 26.9% [n=101]; p=0.039) and an increase in serum creatinine (6.8% [n=11] vs 14.0% [n=52]; p=0.019). No differences in DFS and OS were observed between the two groups (5year DFS 81.9% [CI 74.9%-87.2%] vs 80.8% [76.3%-84.6%]; p=0.850; 5year OS 86.4% [79.9%-90.9%] vs 88.3% [84.4%-91.3%]; p=0.491).
Conclusion: This analysis of patients treated with a dose-dense regimen showed that obese patients who received CT according to their real BSA have a higher risk of severe toxicities, in particular of febrile neutropenia, high grade thrombopenia and high grade thromboembolic events. Therefore, a dose adjustment of intense dose-dense CT should be performed for obese patients to avoid life-threatening complications.
Citation Format: Furlanetto J, Eiermann W, Marmé F, Reimer T, Reinisch M, Schmatloch S, Stickeler E, Thomssen C, Untch M, Denkert C, von Minckwitz G, Nekljudova V, Loibl S, Möbus V. Higher rate of severe toxicities in obese patients receiving dose-dense chemotherapy according to unadjusted body mass index – Results of the prospectively randomized GAIN study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-13-04.