Cisplatin Every 3 Weeks Versus Weekly with Definitive Concurrent Radiotherapy for Squamous Cell Carcinoma of the Head and Neck

Joshua M. Bauml; Ravi Vinnakota; Yeun Hee Anna Park; Susan E. Bates; Tito Fojo; Charu Aggarwal; Sewanti Limaye; Nevena Damjanov; Jessica Di Stefano; Christine Ciunci; Eric M. Genden; Juan P. Wisnivesky; Rocco Ferrandino; Ronac Mamtani; Corey J. Langer; Roger B. Cohen; Keith Sigel

doi:10.1093/jnci/djy133

Cisplatin Every 3 Weeks Versus Weekly with Definitive Concurrent Radiotherapy for Squamous Cell Carcinoma of the Head and Neck

Joshua M. Bauml, Ravi Vinnakota, Yeun Hee Anna Park, Susan E. Bates, Tito Fojo, Charu Aggarwal, Sewanti Limaye, Nevena Damjanov, Jessica Di Stefano, Christine Ciunci, Eric M. Genden, Juan P. Wisnivesky, Rocco Ferrandino, Ronac Mamtani, Corey J. Langer, Roger B. Cohen, Keith Sigel

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Abstract

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.

Original language	English
Article number	djy133
Pages (from-to)	490-497
Number of pages	8
Journal	Journal of the National Cancer Institute
Volume	111
Issue number	5
DOIs	https://doi.org/10.1093/jnci/djy133
State	Published - 1 May 2019

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Bauml, J. M., Vinnakota, R., Anna Park, Y. H., Bates, S. E., Fojo, T., Aggarwal, C., Limaye, S., Damjanov, N., Di Stefano, J., Ciunci, C., Genden, E. M., Wisnivesky, J. P., Ferrandino, R., Mamtani, R., Langer, C. J., Cohen, R. B., & Sigel, K. (2019). Cisplatin Every 3 Weeks Versus Weekly with Definitive Concurrent Radiotherapy for Squamous Cell Carcinoma of the Head and Neck. Journal of the National Cancer Institute, 111(5), 490-497. Article djy133. https://doi.org/10.1093/jnci/djy133

@article{8e2c5835450641acaa2a51424d62ca62,

title = "Cisplatin Every 3 Weeks Versus Weekly with Definitive Concurrent Radiotherapy for Squamous Cell Carcinoma of the Head and Neck",

abstract = "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.",

author = "Bauml, {Joshua M.} and Ravi Vinnakota and {Anna Park}, {Yeun Hee} and Bates, {Susan E.} and Tito Fojo and Charu Aggarwal and Sewanti Limaye and Nevena Damjanov and {Di Stefano}, Jessica and Christine Ciunci and Genden, {Eric M.} and Wisnivesky, {Juan P.} and Rocco Ferrandino and Ronac Mamtani and Langer, {Corey J.} and Cohen, {Roger B.} and Keith Sigel",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2018.",

year = "2019",

month = may,

day = "1",

doi = "10.1093/jnci/djy133",

language = "English",

volume = "111",

pages = "490--497",

journal = "Journal of the National Cancer Institute",

issn = "0027-8874",

publisher = "Oxford University Press",

number = "5",

}

Bauml, JM, Vinnakota, R, Anna Park, YH, Bates, SE, Fojo, T, Aggarwal, C, Limaye, S, Damjanov, N, Di Stefano, J, Ciunci, C, Genden, EM, Wisnivesky, JP, Ferrandino, R, Mamtani, R, Langer, CJ, Cohen, RB & Sigel, K 2019, 'Cisplatin Every 3 Weeks Versus Weekly with Definitive Concurrent Radiotherapy for Squamous Cell Carcinoma of the Head and Neck', Journal of the National Cancer Institute, vol. 111, no. 5, djy133, pp. 490-497. https://doi.org/10.1093/jnci/djy133

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

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 -

Cisplatin Every 3 Weeks Versus Weekly with Definitive Concurrent Radiotherapy for Squamous Cell Carcinoma of the Head and Neck

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