Bjørg Sjøblom1, Bjørn H Grønberg2, Jūratė Šaltytė Benth3, Vickie E Baracos4, Øystein Fløtten5, Marianne J Hjermstad6, Nina Aass7, Marit Jordhøy8. 1. Department of Internal Medicine, Innlandet Hospital Trust, Hamar, Norway; Department of Oncology, Oslo University Hospital, Oslo, Norway. Electronic address: b.sjoblom@hotmail.com. 2. 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. 3. Institute of Clinical Medicine, Campus Ahus, University of Oslo, Norway; HØKH, Research Centre, Akershus University Hospital, Norway. 4. Department of Oncology, Division of Palliative Care Medicine, University of Alberta, Edmonton, Canada. 5. Department of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway. 6. 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. 7. 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. 8. Department of Internal Medicine, Innlandet Hospital Trust, Hamar, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway.
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. CONCLUSION: 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.
RCT Entities:
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. CONCLUSION: 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.
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