TY - JOUR
T1 - Cisplatin Every 3 Weeks Versus Weekly with Definitive Concurrent Radiotherapy for Squamous Cell Carcinoma of the Head and Neck
AU - Bauml, Joshua M.
AU - Vinnakota, Ravi
AU - Anna Park, Yeun Hee
AU - Bates, Susan E.
AU - Fojo, Tito
AU - Aggarwal, Charu
AU - Limaye, Sewanti
AU - Damjanov, Nevena
AU - Di Stefano, Jessica
AU - Ciunci, Christine
AU - Genden, Eric M.
AU - Wisnivesky, Juan P.
AU - Ferrandino, Rocco
AU - Mamtani, Ronac
AU - Langer, Corey J.
AU - Cohen, Roger B.
AU - Sigel, Keith
N1 - Funding Information:
CJL has received honoraria from Bristol-Myers Squibb, Genentech/Roche, and Lilly/ImClone; has served as an advisor for Genentech/Roche, Lilly/ImClone, Merck, Abbott Biotherapeutics, Bayer/Onyx, Clarient, Clovis, Celgene, Cancer Support Community, Bristol-Myers Squibb, Ariad, and Takeda; and provides research support for institutional projects funded by Merck, Advantagene, Clovis Oncology, Celgene, Inovio, Ariad, GlaxoSmithKline, Genentech/Roche, StemCentRx. He has another relationship with Lilly, Amgen, Peregrine Pharmaceuticals, and Synta. RBC has received honoraria from Bristol-Myers Squibb; serves a consulting/advisory role with Heat Biologics, Takeda, Cerulean, GlaxoSmithKline, and
Funding Information:
Zymeworks; provides research support on institutional projects funded by Heat Biologics, Macrogenics, Merck, Takeda, and Cleave Biosciences; and has had travel/accomodations/expenses paid by Heat Biologics, Takeda, Kolltan, Cerulean, and Zymeworks.
Funding Information:
JMB serves as consultant/advisor with Clovis Oncology, Bristol-Myers Squibb, Merck, AstraZeneca, Genentech, Celgene, Boehringer Ingelheim, and Guardant Health, and provides research support on other institutional projects that receive funding from Merck, Janssen, Carevive Systems, Novartis, Incyte, and Bayer. TF serves as consultant or advisor with a Cerulean Pharma advisory board and has received a small amount of royalties from the US government under a long-standing agreement on taxol that has now ended. CA serves as consultant/advisor with Genentech, Bristol Myers Squibb, and Lilly, and provides research support on other institutional projects funded by Genentech/Roche, Incyte, and Macrogenics; an immediate family member is on a speakers’ bureau with Genentech, Novartis, and Pfizer. ND has received honoraria from Sirtex Medical, and serves as consultant/advisor with Bayer, Amgen, and Celgene; an immediate family member has received honoraria from Daiichi Sankyo. JW serves as a consultant with Quintiles, Merck, and AstraZeneca; has received honoraria from EHE International; and provides research support on institutional projects funded by Sanofi and Quorum.
Funding Information:
KS is a recipient of a grant from the National Cancer Institute, K07CA180782.
Publisher Copyright:
© The Author(s) 2018.
PY - 2019/5/1
Y1 - 2019/5/1
N2 - Background: Concurrent chemoradiotherapy is an established component of the nonoperative management of locally advanced head and neck squamous cell carcinoma (HNSCC), but the standard dose of 100mg/m2 cisplatin every 3 weeks is associated with clinically significant toxicity. Interest in a more tolerable regimen has led to the widespread use of weekly lower dose cisplatin, but few randomized trials have compared these approaches. Methods: We examined outcomes of patients with stage III-IVb HNSCC treated with definitive intent chemoradiotherapy using either high-dose cisplatin (HDC) or low-dose cisplatin (LDC), using population-based Veterans Affairs data. In an intentto-treat analysis, patients were assigned to the HDC vs LDC group according to the dose of their first cycle. Variables potentially influencing treatment decisions including cancer site, stage, smoking/alcohol use, and comorbidities were used to generate propensity scores (PS) for the use of HDC. We compared overall survival (OS) by treatment group using Cox regression, adjusting for PS. We then determined the risk of toxicities using PS-Adjusted logistic regression. Results: A total of 2901 patients were included in the analysis; 2200 received HDC (mean initial dose 100mg/m2). The mean initial dose of LDC was 40mg/m2. After PS adjustment, HDC was not associated with improved OS over LDC (hazard ratio = 0.94, 95% confidence interval = 0.80 to 1.04). Adjusting for PS, HDC was associated with an increased risk of acute kidney injury, neutropenia, dehydration/electrolyte disturbance, and hearing loss. Conclusion: In this large, population-based study of US military veterans, LDC was associated with similar survival to HDC in the nonoperative definitive management of locally advanced HNSCC of the oral cavity, oropharynx, and hypopharynx/larynx. HDC was associated with statistically significantly more toxicity than LDC. Adoption of LDC may reduce toxicity burden while maintaining OS.
AB - Background: Concurrent chemoradiotherapy is an established component of the nonoperative management of locally advanced head and neck squamous cell carcinoma (HNSCC), but the standard dose of 100mg/m2 cisplatin every 3 weeks is associated with clinically significant toxicity. Interest in a more tolerable regimen has led to the widespread use of weekly lower dose cisplatin, but few randomized trials have compared these approaches. Methods: We examined outcomes of patients with stage III-IVb HNSCC treated with definitive intent chemoradiotherapy using either high-dose cisplatin (HDC) or low-dose cisplatin (LDC), using population-based Veterans Affairs data. In an intentto-treat analysis, patients were assigned to the HDC vs LDC group according to the dose of their first cycle. Variables potentially influencing treatment decisions including cancer site, stage, smoking/alcohol use, and comorbidities were used to generate propensity scores (PS) for the use of HDC. We compared overall survival (OS) by treatment group using Cox regression, adjusting for PS. We then determined the risk of toxicities using PS-Adjusted logistic regression. Results: A total of 2901 patients were included in the analysis; 2200 received HDC (mean initial dose 100mg/m2). The mean initial dose of LDC was 40mg/m2. After PS adjustment, HDC was not associated with improved OS over LDC (hazard ratio = 0.94, 95% confidence interval = 0.80 to 1.04). Adjusting for PS, HDC was associated with an increased risk of acute kidney injury, neutropenia, dehydration/electrolyte disturbance, and hearing loss. Conclusion: In this large, population-based study of US military veterans, LDC was associated with similar survival to HDC in the nonoperative definitive management of locally advanced HNSCC of the oral cavity, oropharynx, and hypopharynx/larynx. HDC was associated with statistically significantly more toxicity than LDC. Adoption of LDC may reduce toxicity burden while maintaining OS.
UR - http://www.scopus.com/inward/record.url?scp=85063260015&partnerID=8YFLogxK
U2 - 10.1093/jnci/djy133
DO - 10.1093/jnci/djy133
M3 - Article
C2 - 30239887
AN - SCOPUS:85063260015
SN - 0027-8874
VL - 111
SP - 490
EP - 497
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 5
M1 - djy133
ER -