title: 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.
abstract: In routine clinical practice, chemotherapy doses are frequently capped at a body surface area (BSA) of 2.0 m2or adjusted to an ideal weight for obese patients due to safety reasons.
  
  
  
  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.
  
  
  
  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].
  
  
  
  Obese patients 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.
authors: Department of Medicine and Research, German Breast Group, Neu-Isenburg jenny.furlanetto@gbg.de.
authors: J
authors: J
authors: Furlanetto
authors: Department of Gynecologic Oncology, Inter-disciplinary Oncological Center, München.
authors: W
authors: W
authors: Eiermann
authors: Women's Hospital, University Hospital Heidelberg, Heidelberg.
authors: F
authors: F
authors: Marmé
authors: Department of Obstetrics and Gynecology Klinikum Südstadt Rostock, Rostock.
authors: T
authors: T
authors: Reimer
authors: Women's Hospital, Kliniken Essen-Mitte, Essen.
authors: M
authors: M
authors: Reinisch
authors: Department of Gynecologic Oncology, Elisabeth-Krankenhaus Brustzentrum, Kassel.
authors: S
authors: S
authors: Schmatloch
authors: Department of Gynaecology and Obstetrics, Hospital Technische Universität Aachen, Aachen.
authors: E
authors: E
authors: Stickeler
authors: Department of Gynecology, Universitiy Hospital Halle, Saale.
authors: C
authors: C
authors: Thomssen
authors: Department of Gynecology, Helios Klinikum Berlin-Buch, Berlin.
authors: M
authors: M
authors: Untch
authors: Institute of Pathology, Charite Berlin, Berlin.
authors: C
authors: C
authors: Denkert
authors: Department of Medicine and Research, German Breast Group, Neu-Isenburg.
authors: G
authors: G
authors: von Minckwitz
authors: Department of Medicine and Research, German Breast Group, Neu-Isenburg.
authors: B
authors: B
authors: Lederer
authors: Department of Medicine and Research, German Breast Group, Neu-Isenburg.
authors: V
authors: V
authors: Nekljudova
authors: Department of Medicine and Research, German Breast Group, Neu-Isenburg.
authors: K
authors: K
authors: Weber
authors: Department of Medicine and Research, German Breast Group, Neu-Isenburg.
authors: S
authors: S
authors: Loibl
authors: Department of Obstetrics and Gynecology, Klinikum Frankfurt -Hoechst, Frankfurt, Germany.
authors: V
authors: V
authors: Möbus
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D015992:Body Mass Index; D001830:Body Surface Area; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D000069287:Capecitabine / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000008:administration & dosage; D064147:Febrile Neutropenia / Q000139:chemically induced / Q000473:pathology; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D015251:Epirubicin; D000069287:Capecitabine; D003520:Cyclophosphamide
keywords: breast cancer; dose adjustment; dose-dense chemotherapy; obesity; survival; toxicity