Dose-Dense Chemotherapy Adjustment Recommended For Obese Breast Cancer Patients

A full dose of dose-intense chemotherapy increases toxicity in patients with node-positive breast cancer without boosting survival

medwireNews: Dose-dense chemotherapy should be adjusted to take into account a high body mass index (BMI), say researchers who found an excessive risk of toxicity without survival benefit in obese, high-risk breast cancer patients who received a dose calculated strictly by body surface area (BSA).

The team examined results for the 555 participants of the phase III GAIN trial who had a BMI of 30 kg/m2 or above and were randomly assigned to receive the iddETC dose-dense regimen (sequential courses of epirubicin, docetaxel and cyclophosphamide) or the EC-TX regimen (epirubicin plus cyclophosphamide, followed by docetaxel and capecitabine).

In all, 31% of the obese patients received chemotherapy on an unadjusted BSA and the remainder had their dosing calculated according to BSA adjusted to ideal weight or capped at 2.0 m2, explain Jenny Furlanetto, from the German Breast Group in Neu-Isenburg, and co-workers.

Patients who received an unadjusted chemotherapy dose were significantly more likely to develop grade 3–4 febrile neutropenia (14.7 vs 6.3%) and grade 3–4 thrombopenia (9.4 vs 2.9%) than those given an adjusted dose.

And an unadjusted dose was also associated with a significantly higher risk of both grade 1–4 thromboembolism (17.3 vs 9.9%), and grade 3–4 events (12.7 vs 6.3%), and high-grade hot flushes (2.9 vs 0.3%).

Patients given an unadjusted dose, however, did have a significantly lower risk of grade 1–4 symptoms of dizziness (4.6 vs 11.0%), diarrhoea (18.5 vs 27.2%) and serum creatinine elevation (6.6 vs 13.8%) than their adjusted dose counterparts.

Of note, 5-year disease-free survival did not significantly differ between the 2435 trial participants with a normal BMI, the 173 obese patients given unadjusted dose-dense chemotherapy and the 382 obese patients given an adjusted dose, at 81%, 82% and 81%, respectively.

Nor did rates of 5-year overall survival differ between the three groups, at 90%, 86% and 88%, respectively.

“Although several studies agree in showing no higher toxicities in obese patients treated with full dose standard chemotherapy, only little is known on chemotherapy pharmacokinetics and obesity”, the study authors comment in the Annals of Oncology.

“The influence of obesity on drug clearance varies between different metabolic or elimination pathways and depends also on the chemotherapeutic involved”, they explain, resulting in a “lack of predictability” of toxicities.

“Therefore, given the paucity of data on the safety of obese patients treated with [dose-dense] chemotherapy, and the absence of an impact of dose adjustment on survival, a conservative approach should be followed to avoid life-threatening complications”, the team recommends.

References

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; Advance online publication 8 August. doi: 10.1093/annonc/mdw315

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