The association of body mass index with safety and effectiveness of first-line carboplatin-based chemotherapy in patients with metastatic non-small cell lung cancer

Introduction: Carboplatin is an anticancer drug used for treatment of various types of cancer including non-small cell lung cancer (NSCLC). Dosing is based on estimated glomerular filtration rate (GFR) using the Cockcroft-Gault formula. In overweight patients, the GFR is more likely overestimated, r...

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Main Authors: M.P. Kicken, H.D. Kilinc, C.M. Cramer-van der Welle, S. Houterman, B.E.E.M. van den Borne, A.A.J. Smit, E.M.W. van de Garde, M.J. Deenen
Format: Article
Language:English
Published: Elsevier 2023-01-01
Series:Cancer Treatment and Research Communications
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2468294222001678
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author M.P. Kicken
H.D. Kilinc
C.M. Cramer-van der Welle
S. Houterman
B.E.E.M. van den Borne
A.A.J. Smit
E.M.W. van de Garde
M.J. Deenen
author_facet M.P. Kicken
H.D. Kilinc
C.M. Cramer-van der Welle
S. Houterman
B.E.E.M. van den Borne
A.A.J. Smit
E.M.W. van de Garde
M.J. Deenen
author_sort M.P. Kicken
collection DOAJ
description Introduction: Carboplatin is an anticancer drug used for treatment of various types of cancer including non-small cell lung cancer (NSCLC). Dosing is based on estimated glomerular filtration rate (GFR) using the Cockcroft-Gault formula. In overweight patients, the GFR is more likely overestimated, resulting in a potentially overdose of carboplatin affecting treatment response. This study investigated the association of body mass index (BMI) on overall survival (OS) and progression-free survival (PFS) in stage-IV NSCLC patients treated with first-line carboplatin-based chemotherapy. Secondary safety endpoints were thrombocytopenia and toxicity-related hospitalizations. Materials and methods: This was a retrospective multicenter cohort study. Patients were categorized according to BMI<25.0 kg/m2 (normal weight and reference), 25.0-29.9 kg/m2 (overweight) or ≥30.0 kg/m2 (obese). For survival analyses adjusted hazard ratios [aHR] were calculated using multivariate Cox regression analysis. Secondary outcomes were analyzed using multivariate logistic regression providing adjusted odd ratios [aOR]. Results: Overweight patients (n=174) had a significantly better OS (aHR=0.72, 95%-CI:0.59-0.89) and PFS (aHR=0.74, 95%-CI:0.61-0.90) compared to normal weight patients (n=268). OS nor PFS were different in obese (n=51) compared to normal weight patients. However, obesity was associated with significantly higher incidences of thrombocytopenia grade ≥3 (aOR=3.47, 95%-CI:1.75-6.90). Conclusion: This study shows a significantly longer survival for overweight compared to normal weight patients. Obese patients have an increased risk for grade ≥3 thrombocytopenia without a difference in survival following carboplatin-based chemotherapy. The implications for clinical practice are to use the Cockcroft-Gault formula with caution in patients with BMI≥30.0 kg/m2, and to verify calculated dosing of carboplatin for appropriateness.
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spelling doaj.art-f9bd66ceb6a641ff899150515f489eec2023-01-28T04:08:08ZengElsevierCancer Treatment and Research Communications2468-29422023-01-0134100676The association of body mass index with safety and effectiveness of first-line carboplatin-based chemotherapy in patients with metastatic non-small cell lung cancerM.P. Kicken0H.D. Kilinc1C.M. Cramer-van der Welle2S. Houterman3B.E.E.M. van den Borne4A.A.J. Smit5E.M.W. van de Garde6M.J. Deenen7Department of Clinical Pharmacy, Catharina Hospital, Eindhoven, The NetherlandsDepartment of Clinical Pharmacy, Catharina Hospital, Eindhoven, The NetherlandsSanteon Hospital Group, Utrecht, The NetherlandsDepartment of Education and Research, Catharina Hospital, The NetherlandsDepartment of Pulmonology, Catharina Hospital, The NetherlandsDepartment of Pulmonary Medicine, OLVG Hospital, The NetherlandsDepartment of Clinical Pharmacy, St. Antonius Hospital, The Netherlands; Division of Pharmacoepidemiology and Clinical Pharmacology, Department of Pharmaceutical Sciences, Utrecht University, The NetherlandsDepartment of Clinical Pharmacy, Catharina Hospital, Eindhoven, The Netherlands; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, The NetherlandsIntroduction: Carboplatin is an anticancer drug used for treatment of various types of cancer including non-small cell lung cancer (NSCLC). Dosing is based on estimated glomerular filtration rate (GFR) using the Cockcroft-Gault formula. In overweight patients, the GFR is more likely overestimated, resulting in a potentially overdose of carboplatin affecting treatment response. This study investigated the association of body mass index (BMI) on overall survival (OS) and progression-free survival (PFS) in stage-IV NSCLC patients treated with first-line carboplatin-based chemotherapy. Secondary safety endpoints were thrombocytopenia and toxicity-related hospitalizations. Materials and methods: This was a retrospective multicenter cohort study. Patients were categorized according to BMI<25.0 kg/m2 (normal weight and reference), 25.0-29.9 kg/m2 (overweight) or ≥30.0 kg/m2 (obese). For survival analyses adjusted hazard ratios [aHR] were calculated using multivariate Cox regression analysis. Secondary outcomes were analyzed using multivariate logistic regression providing adjusted odd ratios [aOR]. Results: Overweight patients (n=174) had a significantly better OS (aHR=0.72, 95%-CI:0.59-0.89) and PFS (aHR=0.74, 95%-CI:0.61-0.90) compared to normal weight patients (n=268). OS nor PFS were different in obese (n=51) compared to normal weight patients. However, obesity was associated with significantly higher incidences of thrombocytopenia grade ≥3 (aOR=3.47, 95%-CI:1.75-6.90). Conclusion: This study shows a significantly longer survival for overweight compared to normal weight patients. Obese patients have an increased risk for grade ≥3 thrombocytopenia without a difference in survival following carboplatin-based chemotherapy. The implications for clinical practice are to use the Cockcroft-Gault formula with caution in patients with BMI≥30.0 kg/m2, and to verify calculated dosing of carboplatin for appropriateness.http://www.sciencedirect.com/science/article/pii/S2468294222001678OverweightBMINSCLCOverdosingToxicitySurvival
spellingShingle M.P. Kicken
H.D. Kilinc
C.M. Cramer-van der Welle
S. Houterman
B.E.E.M. van den Borne
A.A.J. Smit
E.M.W. van de Garde
M.J. Deenen
The association of body mass index with safety and effectiveness of first-line carboplatin-based chemotherapy in patients with metastatic non-small cell lung cancer
Cancer Treatment and Research Communications
Overweight
BMI
NSCLC
Overdosing
Toxicity
Survival
title The association of body mass index with safety and effectiveness of first-line carboplatin-based chemotherapy in patients with metastatic non-small cell lung cancer
title_full The association of body mass index with safety and effectiveness of first-line carboplatin-based chemotherapy in patients with metastatic non-small cell lung cancer
title_fullStr The association of body mass index with safety and effectiveness of first-line carboplatin-based chemotherapy in patients with metastatic non-small cell lung cancer
title_full_unstemmed The association of body mass index with safety and effectiveness of first-line carboplatin-based chemotherapy in patients with metastatic non-small cell lung cancer
title_short The association of body mass index with safety and effectiveness of first-line carboplatin-based chemotherapy in patients with metastatic non-small cell lung cancer
title_sort association of body mass index with safety and effectiveness of first line carboplatin based chemotherapy in patients with metastatic non small cell lung cancer
topic Overweight
BMI
NSCLC
Overdosing
Toxicity
Survival
url http://www.sciencedirect.com/science/article/pii/S2468294222001678
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