J Furlanetto1, W Eiermann2, F Marmé3, T Reimer4, M Reinisch5, S Schmatloch6, E Stickeler7, C Thomssen8, M Untch9, C Denkert10, G von Minckwitz11, B Lederer11, V Nekljudova11, K Weber11, S Loibl11, V Möbus12. 1. Department of Medicine and Research, German Breast Group, Neu-Isenburg jenny.furlanetto@gbg.de. 2. Department of Gynecologic Oncology, Inter-disciplinary Oncological Center, München. 3. Women's Hospital, University Hospital Heidelberg, Heidelberg. 4. Department of Obstetrics and Gynecology Klinikum Südstadt Rostock, Rostock. 5. Women's Hospital, Kliniken Essen-Mitte, Essen. 6. Department of Gynecologic Oncology, Elisabeth-Krankenhaus Brustzentrum, Kassel. 7. Department of Gynaecology and Obstetrics, Hospital Technische Universität Aachen, Aachen. 8. Department of Gynecology, Universitiy Hospital Halle, Saale. 9. Department of Gynecology, Helios Klinikum Berlin-Buch, Berlin. 10. Institute of Pathology, Charite Berlin, Berlin. 11. Department of Medicine and Research, German Breast Group, Neu-Isenburg. 12. Department of Obstetrics and Gynecology, Klinikum Frankfurt -Hoechst, Frankfurt, Germany.
Abstract
BACKGROUND: In routine clinical practice, chemotherapy doses are frequently capped at a body surface area (BSA) of 2.0 m2 or adjusted to an ideal weight for obese patients due to safety reasons. MATERIALS AND 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 (dd) regimen [epirubicin, docetaxel and cyclophosphamide (iddETC) versus epirubicin and cyclophosphamide (EC) followed by docetaxel (T) plus capecitabine (X)]. We retrospectively evaluated a total of 555 patients with a BMI of ≥30 for safety and outcome. RESULTS: Eighteen percent of all patients were obese: 31% of those received chemotherapy according to an unadjusted BSA. For the remaining patients, BSA was adjusted to ideal weight or was capped at 2.0 m2. A total of 15% of obese patients receiving full (unadjusted) dose of chemotherapy versus 6% of obese patients with an adjusted BSA experienced febrile neutropenia (P = 0.003) and 9% versus 3% high-grade thrombopenia (P = 0.002). Overall, 17% versus 10% had a thromboembolic event (P = 0.017), which was high grade in 13% versus 6%, respectively (P = 0.019), and 3% versus 0.3% high-grade hot flushes (P = 0.013). Dizziness (5% versus 11%; P = 0.016), diarrhea (19% versus 27%; P = 0.033) and an increase in serum creatinine (7% versus 14%; P = 0.019) were higher in the adjusted group. However, no differences in disease-free survival (DFS) and overall survival (OS) were observed between non-obese patients, obese patients receiving full-dose chemotherapy or according to an adjusted BSA [5-year DFS 81% (confidence interval 79% to 83%) versus 82% (75% to 87%) versus 81% (76% to 84%); P = 0.761; 5-year OS 90% (88% to 91%) versus 86% (80% to 91%) versus 88% (84% to 91%); P = 0.143]. CONCLUSION:Obese patients receivingdd chemotherapy according to their real BSA have a higher risk of developing severe toxicities without influencing survival. Therefore, a dose adjustment of intense dd chemotherapy should be carried out to avoid life-threatening complications.
RCT Entities:
BACKGROUND: In routine clinical practice, chemotherapy doses are frequently capped at a body surface area (BSA) of 2.0 m2 or adjusted to an ideal weight for obesepatients due to safety reasons. MATERIALS AND 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 (dd) regimen [epirubicin, docetaxel and cyclophosphamide (iddETC) versus epirubicin and cyclophosphamide (EC) followed by docetaxel (T) plus capecitabine (X)]. We retrospectively evaluated a total of 555 patients with a BMI of ≥30 for safety and outcome. RESULTS: Eighteen percent of all patients were obese: 31% of those received chemotherapy according to an unadjusted BSA. For the remaining patients, BSA was adjusted to ideal weight or was capped at 2.0 m2. A total of 15% of obesepatients receiving full (unadjusted) dose of chemotherapy versus 6% of obesepatients with an adjusted BSA experienced febrile neutropenia (P = 0.003) and 9% versus 3% high-grade thrombopenia (P = 0.002). Overall, 17% versus 10% had a thromboembolic event (P = 0.017), which was high grade in 13% versus 6%, respectively (P = 0.019), and 3% versus 0.3% high-grade hot flushes (P = 0.013). Dizziness (5% versus 11%; P = 0.016), diarrhea (19% versus 27%; P = 0.033) and an increase in serum creatinine (7% versus 14%; P = 0.019) were higher in the adjusted group. However, no differences in disease-free survival (DFS) and overall survival (OS) were observed between non-obesepatients, obesepatients receiving full-dose chemotherapy or according to an adjusted BSA [5-year DFS 81% (confidence interval 79% to 83%) versus 82% (75% to 87%) versus 81% (76% to 84%); P = 0.761; 5-year OS 90% (88% to 91%) versus 86% (80% to 91%) versus 88% (84% to 91%); P = 0.143]. CONCLUSION:Obesepatients receiving dd chemotherapy according to their real BSA have a higher risk of developing severe toxicities without influencing survival. Therefore, a dose adjustment of intense dd chemotherapy should be carried out to avoid life-threatening complications.
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