PracticeUpdate: Oncology - Winter 2018

EDITOR’S PICKS 10

Clinical Consequences of Chemotherapy Dose Reduction in Obese Patients With Stage III Colon Cancer European Journal of Cancer

of using fully dosed chemotherapy for the adju- vant treatment in obese patients with colon cancer. Clinical Consequences of Chemotherapy Dose Reduction in Obese Patients With Stage III Colon Cancer: A Retrospective Analysis From the PETACC 3 Study. Eur J Cancer 2018 Aug 01;99(xx)49-57, G Stocker, UT Hacker, F Fiteni, et al. www.practiceupdate.com/c/69620 " …dose reductions should not be applied preemptively in overweight/obese patients unless other factors such as renal or hepatic function come into play. " COMMENT By Axel Grothey MD T he appropriate dosing of chemo- therapy in obese patients has long been a topic of discussion. Espe- cially in extremely obese patients, the calculated absolute dose of chemo- therapy can sometimes induce a “sticker-shock” andmight lead to a reflex dose reduction or a policy of capping BSA calculations at 2.0. In a palliative setting, potential mild under-dosing might not be as critical; but, in a curative, adjuvant setting, optimization of chemo- therapy dosing is a critical component of the treatment approach. In the current retrospective analysis of the adjuvant PETACC-3 trial in colon cancer, upfront dose reduction in obese patients was associated with decreased relapse-free survival in women, and, with a nonsig- nificant trend, also in men. These data add to the current body of evidence that dose reductions should not be applied preemptively in overweight/obese patients unless other factors such as renal or hepatic function come into play.

Take-home message • This retrospective study looked at the impact of dose reduction among obese patients treated with adjuvant chemotherapy for stage III colon cancer. Among patients with BMI ≥30 and a body surface area ≥2 m 2 , relapse-free survival was longer for those fully dosed vs dose-reduced (HR, 0.48), and there was a trend toward improved overall survival (HR, 0.53; P = .052). • The study authors concluded that it is appropriate to recommend fully dosed chemotherapy in the adjuvant setting for obese patients with colon cancer. Neil Majithia MD

Abstract BACKGROUND Dose reduction in obese cancer patients has been replaced by fully weight- based dosing recommendations. No data, however, are available on the effects of dose reduction in obese stage III colon cancer patients undergoing adjuvant chemotherapy. METHODS Survival outcomes and toxicity data of obese (body mass index [BMI] ≥30 kg/m 2 ), stage III colon cancer patients treated within the phase III PETACC 3 trial comparing leucov- orin, 5-FU (LV5FU2) with LV5FU2 plus irinotecan were analysed retrospectively according to chemotherapy dosing at first infusion (i.e. fully weight-based dosed – versus dose-reduced group). Multivariate analyses on relapse free survival (RFS) and overall survival (OS) were con- ducted to adjust for baseline prognostic factors using Cox regression model.

RESULTS 13.4% (280 of 2094 patients) had a BMI ≥30 kg/m 2 , and 5.3% had both a BMI ≥30 kg/ m 2 and a body surface area (BSA) ≥2 m 2 . Dose reductions occurred in 16.1% of patients with a BMI ≥30 kg/m 2 and 32.4% with BMI ≥ 30kg/m 2 and BSA ≥2 m 2 , respectively. In patients with BMI ≥30 kg/m 2 , multivariate analysis demonstrated a trend towards better RFS in the fully dosed com- pared to the dose-reduced group (Hazard ratio (HR): 0.69, 95% CI: 0.43-1.09; p = 0.11); however, there was no statistically significant difference in OS. In patients with BMI ≥30 kg/m 2 and BSA ≥2 m 2 , multivariate analysis demonstrated better RFS in fully dosed compared with dose-reduced patients (HR: 0.48, 95% CI: 0.27-0.85; p = 0.01) and a strong trend towards better OS (HR: 0.53, 95% CI: 0.28-1.01; p = 0.052). This group com- prised predominantly of men. CONCLUSIONS Data support the recommendation

PRACTICEUPDATE ONCOLOGY