Managing Toxicity Risks of Dose-Dense Chemotherapy in the Obese

Managing Toxicity Risks of Dose-Dense Chemotherapy in the Obese
Managing Toxicity Risks of Dose-Dense Chemotherapy in the Obese

Using actual body surface area (BSA) to determine doses of dose-dense chemotherapy for obese patients increases their risk of severe toxicities, according to results of a study published in the journal Annals of Oncology.1

For safety reasons, chemotherapy doses are capped at BSA of 2.0 m2 or adjusted to an ideal weight for obese patients. In this study, researchers conducted a retrospective evaluation of patients enrolled in the GAIN study to determine safety and outcome of these measures vs unadjusted BSA in those patients with a body mass index (BMI) of 30 or greater.

The GAIN study was a randomized phase III adjuvant trial that compared 2 types of dose-dense regimen: epirubicin, docetaxel, and cyclophosphamide (iddETC) and epirubicin and cyclophosphamide (EC) followed by docetaxel (T) plus capecitabine (X).

Of the 3023 patients enrolled in the GAIN study, 555 patients (18%) were obese; 31% of whom received chemotherapy based on an unadjusted BSA. Doses for the remaining patients were adjusted to ideal weight or capped at a BSA of 2.0 m2.

Results revealed higher rates of severe toxicities in the obese patients receiving unadjusted dose of chemotherapy vs those who received an adjusted dose, respectively, including febrile neutropenia (15% vs 6%; P =.003); high-grade thrombopenia (9% vs 3%; P =.002); a thromboembolic event (17% vs 10%; P =.017), with high-grade event at 13% vs 6% (P =.019); and high grade hot flushes (3% vs 0.3%; P =.013).

However, the adjusted group experienced higher rates of dizziness (5% vs 11%; P =.016), diarrhea (19% vs 27%; P =.033), and increased serum creatinine (7% vs 14%; P =.019).

No differences were observed between nonobese patients, obese patients receiving full dose chemotherapy, and obese patients receiving adjusted dose chemotherapy in 5-year disease-free survival (81% [CI 79%-83%] vs 82% [75%-87%] vs 81% [76%-84%], respectively; P=0.761) or 5-year overall survival (90% [88%-91%] vs 86% [80%-91%] vs 88% [84%-91%], respectively; P=0.143).

Based on these results, the researchers conclude that risk of developing severe toxicities is higher for obese patients who receive dose-dense chemotherapy based on their actual BSA. Therefore, adjusting the dose to an ideal weight or capped at BSA 2.0 m2 is suggested.


1. Furlanetto J, Eiermann W, Marmé F, et al. Higher rate of severe toxicities in obese patients receiving dose-dense (dd) chemotherapy according to unadjusted body surface area – results of the prospectively randomized GAIN study. Ann Oncol. 2016 Aug 8. doi: 10.1093/annonc/mdw315. [Epub ahead of print].

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