title: Low muscle mass is associated with chemotherapy-induced haematological toxicity in advanced non-small cell lung cancer.
abstract: BACKGROUND
  Recent research suggests a significant relationship between lean body mass (LBM) and toxicity from chemotherapeutic agents. We investigated if higher drug doses per kg LBM were associated with increased toxicity in stage IIIB/IV non-small cell lung cancer (NSCLC) patients receiving a first-line chemotherapy regimen dosed according to body surface area (BSA).
  
  
  METHODS
  Data from patients randomised to receive intravenous gemcitabine 1000 mg/m(2) plus orally vinorelbine 60 mg/m(2) days 1 and 8 in a phase III trial comparing two chemotherapy regimens were analysed. LBM was estimated from assessment of the cross-sectional muscle area at the third lumbar level (L3) on computed tomography images obtained before chemotherapy commenced. Common terminology criteria for adverse events (CTCAE) grade 3-4 haematological toxicity and dose reduction and/or stop of treatment after the first course of chemotherapy were defined as primary and secondary toxicity outcomes.
  
  
  RESULTS
  The study sample included 153 patients, mean age was 66 years, 55% were men, 87% had disease stage IV and 75% had performance status (PS) 0-1. Gemcitabine doses per kg LBM varied from 23.2 to 53.1 mg/kg LBM, and vinorelbine doses from 1.5 to 3.3 mg/kg LBM. Higher doses of gemcitabine per kg LBM were significantly associated with grade 3-4 haematological toxicity in bivariate (OR=1.12, 95% CI 1.03-1.23, p=0.008) and multivariate analyses (OR=1.15, 95% CI 1.01-1.29, p=0.018), as were also higher doses of vinorelbine per kg LBM. No significant association was found between drug doses per kg LBM and dose reduction and/or stop of treatment.
  
  
  CONCLUSIONS
  The study showed that dose estimates according to BSA lead to a substantial variation in drug dose per kg LBM, and higher doses per kg LBM are a significant predictor for chemotherapy-induced haematological toxicity. The results indicate that taking LBM into account may lead to a better dose individualisation of chemotherapy.
authors.affiliation: Department of Internal Medicine, Innlandet Hospital Trust, Hamar, Norway; Department of Oncology, Oslo University Hospital, Oslo, Norway. Electronic address: b.sjoblom@hotmail.com.
authors.forename: Bjørg
authors.initials: B
authors.lastname: Sjøblom
authors.affiliation: The Cancer Clinic, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; European Palliative Care Research Centre, Dept of Cancer Research and Molecular Medicine, Faculty of Medicine, NTNU, Trondheim, Norway.
authors.forename: Bjørn H
authors.initials: BH
authors.lastname: Grønberg
authors.affiliation: Institute of Clinical Medicine, Campus Ahus, University of Oslo, Norway; HØKH, Research Centre, Akershus University Hospital, Norway.
authors.forename: Jūratė Šaltytė
authors.initials: JŠ
authors.lastname: Benth
authors.affiliation: Department of Oncology, Division of Palliative Care Medicine, University of Alberta, Edmonton, Canada.
authors.forename: Vickie E
authors.initials: VE
authors.lastname: Baracos
authors.affiliation: Department of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Fløtten
authors.affiliation: European Palliative Care Research Centre, Dept of Cancer Research and Molecular Medicine, Faculty of Medicine, NTNU, Trondheim, Norway; Regional Centre for Excellence in Palliative Care, South Eastern Norway, Oslo University Hospital, Oslo, Norway.
authors.forename: Marianne J
authors.initials: MJ
authors.lastname: Hjermstad
authors.affiliation: Regional Centre for Excellence in Palliative Care, South Eastern Norway, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway.
authors.forename: Nina
authors.initials: N
authors.lastname: Aass
authors.affiliation: Department of Internal Medicine, Innlandet Hospital Trust, Hamar, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway.
authors.forename: Marit
authors.initials: M
authors.lastname: Jordhøy
mesh_terms: D061605:Administration, Intravenous; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D003430:Cross-Sectional Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D060828:Induction Chemotherapy; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D018482:Muscle, Skeletal / Q000033:anatomy & histology* / Q000187:drug effects / Q000473:pathology*; D009367:Neoplasm Staging; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D014747:Vinblastine; D000077235:Vinorelbine; D000093542:Gemcitabine
keywords: Body composition; Chemotherapy toxicity; Drug therapy; Haematological toxicity; Lean body mass; Non-small cell lung cancer; Skeletal muscle; Wasting syndrome