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Top Takeaways from ASCO: Therapeutic dosing in head and neck cancer
Increased utilization of low-dose, weekly regimens of cisplatin may not be efficacious.
CHICAGO — Cisplatin administered in a low-dose, weekly regimen may not be equivalent to standard high-dose, intermittent cisplatin in locally advanced head and neck squamous cell carcinoma, according to two studies presented during a poster session on head and neck cancer at the ASCO Annual Meeting.
Differential impact of cisplatin dose intensity
The first study — a retrospective analysis conducted by Anna Spreafico, MD, PhD, clinical research fellow at Princess Margaret Cancer Centre in Toronto, and colleagues — examined the impact of dose intensity on OS among patients treated with definitive radiation and concurrent cisplatin.
The analysis included 659 patients. The median total dose of concurrent cisplatin was 200 mg/m2 for both HPV-positive and HPV-negative cohorts. Median follow-up was 4.3 years.
The researchers examined the usual prognostic features in locally advanced head and neck squamous cell carcinoma, but they also included total cisplatin dose as part of the investigation, said David Adelstein, MD, staff physician in the department of hematology and medical oncology at Taussig Cancer Institute at Cleveland Clinic and professor of medicine at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University.
David Adelstein
The results show “quite clearly that those patients who were HPV negative had a significantly inferior survival if their dose of cisplatin was below 200 milligrams per square meter,” Adelstein, a HemOnc Today Editorial Board member, told Healio.com. “Except for the worst prognosis HPV-positive patients, in whom a similar trend was identified, this difference was not seen in the HPV-positive cohort. A multivariable analysis including other known prognostic markers confirmed these findings.”
The results of Spreafico and colleagues “reinforce previously reported observations about the importance of cisplatin dose intensity in definitive, concurrent, cisplatin-based chemoradiotherapy regimens,” Adelstein said.
Utilization and outcomes of low-dose vs. high-dose cisplatin
Stuart Wong, MD, associate professor of medicine and otolaryngology in the division of hematology and oncology at the Medical College of Wisconsin, and colleagues also presented research that examined dose intensity in locally advanced head and neck squamous cell carcinoma.
The researchers used the Longitudinal Oncology Registry of Head and Neck Carcinoma — a prospective, observational registry — to identify 1,091 patients treated with definitive concurrent radiation and single-agent cisplatin.
The investigators categorized these patients by whether they received a weekly low-dose cisplatin regimen (≤ 40 mg/m2 per week; n= 334) or a high-dose intermittent cisplatin schedule (≥ 75 mg/m2 every 3 weeks; n = 757).
The total cumulative dose of cisplatin was 322.5 mg for the low-dose group and 475.8 for the high-dose group, a statistically significant difference (P < .001) even when propensity score adjusted for differences between the patient populations.
Results also showed a significant difference in OS favoring the high-dose intermittent group (log rank test, P < .001), although this analysis was limited by incomplete follow-up data, the researchers said.
“What was interesting, and of concern, was that even though weekly low-dose cisplatin is generally felt to be better tolerated, and equally efficacious, patients treated with weekly low-dose cisplatin actually received less total drug and, perhaps because of this lower dose, appeared to have an inferior survival,” Adelstein told Healio.com.
Potential impact for care
When taken together, these trials suggest caution when substituting weekly low-dose cisplatin for standard-of-care high-dose intermittent treatment, Adelstein said.
“Both dose intensity and treatment outcomes may be inferior,” he said. – by Julia Ernst, MS
References:
The following were presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.
Spreafico A, et al. Abstract 6020.
Wong SJ, et al. Abstract 6019.
Disclosure: Adelstein reports no relevant financial disclosures.