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Low- vs High-Dose Cisplatin Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck

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Key Points

  • In propensity score–adjusted analysis, high-dose cisplatin was not associated with significantly better overall survival.
  • Greater risk of toxicity remained with high-dose cisplatin after propensity score–adjusted analysis.

In an analysis of Veterans Affairs data reported in the Journal of the National Cancer Institute, Bauml et al found that weekly lower-dose cisplatin vs higher-dose cisplatin given every 3 weeks as part of concurrent definitive chemoradiotherapy may not adversely affect survival, while reducing toxicity.

The study involved 2,901 patients with stage III to IVb disease treated with definitive-intent chemoradiotherapy using either high-dose cisplatin every 3 weeks (n = 2,200, mean initial dose = 100 mg/m2) or weekly low-dose cisplatin (n = 701, mean initial dose = 40 mg/m2) between 2000 and 2014. Mean cumulative doses were 215 mg/m2 in the high-dose group and 145 mg/m2 in the low-dose group.

Factors affecting treatment decisions including cancer site, stage, smoking/alcohol use, and comorbidities were used to generate propensity scores for the use of high-dose cisplatin, with propensity score–adjusted outcomes being analyzed. The primary disease site of patients differed, with the oral cavity being the site in 183 patients, the oropharynx in 1,908, and the hypopharynx/larynx in 810.

Overall Survival and Toxicity Analysis

In unadjusted analysis, median overall survival was 49 months in the high-dose cisplatin group vs 42 months in the low-dose cisplatin group (hazard ratio [HR] = 0.90, P = .03), with a significant benefit among primary sites observed only for the oropharynx (HR = 0.87, P= .046). On propensity score–adjusted analysis, high-dose cisplatin was not associated with a signifcant survival benefit among the entire cohort (HR = 0.94, 95% confidence interval [CI] =0.80–1.04), at the oropharynx (HR = 0.90, 95% CI = 0.79–1.04), or at any other primary site.

In an unadjusted analysis, high-dose cisplatin was associated with a greater incidence of acute kidney injury, neutropenia, nausea/emesis, dehydration/electrolyte disturbance, and hearing loss. On propensity score–adjusted analysis, elevated risk remained with high-dose cisplatin for acute kidney injury (HR = 1.72, P <.001), neutropenia (HR = 2.21, P = .005), dehydration/electrolyte disturbance (HR = 1.15, P = .04), and hearing loss (HR = 1.34, P = .004).

The investigators concluded, “In this large, population-based study of U.S. military veterans, [low-dose cisplatin] was associated with similar survival to [high-dose cisplatin] in the nonoperative definitive management of locally advanced [head and neck squamous cell carcinoma] of the oral cavity, oropharynx, and hypopharynx/larynx. [High-dose cisplatin] was associated with statistically significantly more toxicity than [low-dose cisplatin]. Adoption of [low-dose cisplatin] may reduce toxicity burden while maintaining [overall survival].”

Joshua M. Bauml, MD, of the Department of Medicine, Division of Hematology/Oncology, Perelman School of Medicine at the University of Pennsylvania, is the corresponding author for the Journal of the National Cancer Institute article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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