By Farzan Siddiqui, MD, PhD, CPE, Henry Ford Hospital
The role of concurrent cisplatin with radiation therapy for the treatment of locally advanced squamous cell carcinoma of the head and neck was established in the late 1990s and early 2000s with a series of well-designed and conducted randomized clinical trials. A meta-analysis of 107 such trials has confirmed the superiority of this approach in improving overall survival.1 However, the addition of cisplatin has also increased the side effect profile of this regimen. Cisplatin is associated with a multitude of short-term side effects and long-term complications such as hematologic toxicity, nephrotoxicity and ototoxicity. The traditional cisplatin regimen involved administering this drug at a dose of 100mg/m2 every three weeks during the seven-week course of radiation therapy. Many patients are unable to receive all three planned cycles due to acute toxicities. This led to the exploration of giving cisplatin at a dose of 40mg/m2 to try to minimize toxicities while maintaining the same overall survival improvement as compared to radiation therapy alone in these patients. A series of recent trials have compared the two chemotherapy regimens. The survival outcomes are comparable between the two regimens based on a meta-analysis of 59 such trials.2 However, there is less clarity for which of these regimens is less toxic overall and has better compliance with somewhat conflicting results.
This RADIO trial, conducted by Winquist et al., studied these two cisplatin regimens in a randomized controlled manner with incidence of hearing loss and hearing-related quality of life as co-primary endpoints. Objective hearing loss was assessed using audiometry at baseline and at three, six and 12 months post-treatment. Subjective hearing loss was assessed using the Hearing Handicap Inventory. They enrolled 99 patients. Most patients (87%) had oropharyngeal cancers and were treated to a radiation dose of 70 Gy in 35 fractions. The mean dose of cisplatin was similar in the two arms and was more than 200mg/m2. Based on previous analyses, this has been established as the minimum required threshold dose for concurrent cisplatin to be effective.3 In the three-weekly arm, about three-fourths of the patients received all three cycles, while in the weekly arm, the median number of cycles was six. The authors presented data on acute toxicity and did not note any significant difference in rates of any grade, and grade ≥3 were similar between the two arms. Some differences in patterns of acute toxicities between the two arms was noted. Data on the primary endpoint of hearing loss as noted on audiometry and quality of life endpoints at one year is currently being analyzed.
This trial studied a very specific and important endpoint of cisplatin-induced ototoxicity. An ongoing phase II/III trial by the NRG Oncology group (NRG HN009) is also evaluating this as a secondary endpoint. Objective hearing loss is being measured using audiograms, and subjective hearing loss-related quality of life is being evaluated using the Hearing Handicap Inventory-Screening (HHIA-S) tool. The total planned accrual for this trial is 1,250 patients. Investigators are encouraged to consider enrolling eligible patients in this trial.
Abstract 12, Acute Toxicity Results from the Randomized Assessment of Cisplatin Dosing Interval for Ototoxicity (RADIO) Trial Comparing Chemoradiation (CRT) with Cisplatin Q3weekly to Weekly for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (LASCCHN), was presented during the Plenary II session at the 2024 Multidisciplinary Head and Neck Cancers Symposium on March 1, 2024.
References
1. Lacas B, Carmel A, Landais C, et al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group. Radiother Oncol. 2021;156:281-293.
2. Szturz P, Wouters K, Kiyota N, et al. Low-Dose vs. High-Dose Cisplatin: Lessons Learned From 59 Chemoradiotherapy Trials in Head and Neck Cancer. Front Oncol. 2019;9:86.
3. Strojan P, Vermorken JB, Beitler JJ, et al. Cumulative cisplatin dose in concurrent chemoradiotherapy for head and neck cancer: A systematic review. Head Neck. 2016;38 Suppl 1:E2151-8.
