Docetaxel as an alternative to cisplatin for radiotherapy H&N

For patients with head and squamous cell carcinoma of the neck who do not tolerate platinum chemotherapy, docetaxel is a good alternative for improving sensitivity to radiation therapy, say researchers reporting a phase 3 trial from India.

“This is the first randomized study demonstrating the benefit of another radiosensitizing agent in patients not eligible for cisplatin,” they point out.

“We found that the use of docetaxel as a radiosensitizer in cisplatin-ineligible patients,” compared to the use of radiotherapy alone, “results in improved disease-free survival, locoregional control, and overall disease-free survival. affect patients’ quality of life,” the team reports.

Investigators, led by Vijay Maruti Patil, MD, DMa medical oncologist at Tata Memorial Hospital in Mumbai, noted that they stopped the trial shortly after the benefits of adding docetaxel became apparent.

Cisplatin is the general standard of care for sensitizing locally advanced head and neck tumors to radiation therapy, but up to a third of patients are ineligible due to age, decreased kidney function, hearing lossand other issues, they point out.

Many alternatives to cisplatin are used in such settings, but so far there has been no level 1, phase 3 evidence to guide selection.

Cetuximab is the most commonly used alternative in the United States, but supporting evidence has been generated in trials involving cisplatin-eligible patients, the researchers point out. There is also a high incidence of skin and other toxicities and, in some studies, less than ideal survival outcomes, they note.

The new study was published online on December 9 in the Journal of Clinical Oncology.

This “demonstrates what might be presumed but was not known to be true in the inadmissible cisplatin context: radiosensitizers improve outcomes compared to radiotherapy alone”, comment the authors of a accompanying editorial.

“Docetaxel belongs to the therapeutic arsenal of reference diets,” they state. The authors are radiation oncologists Loren Mell, MDfrom the University of California, San Diego, and medical oncologist Stuart Wong, MDfrom the Medical College of Wisconsin, Milwaukee.

This study “fills an important gap in the head and neck cancer literature, but “since [docetaxel] has not been compared head-to-head with “other radiosensitizer alternatives, it” should not be stated as the only standard… It is high time to shift the conversation to whether radiosensitizers are beneficial on what diet (the where applicable) provides the most benefit and should set the standard of care,” they add.

Study details

The trial randomly assigned 356 cisplatin-ineligible adults equally to radiation therapy alone or radiation therapy with concomitant docetaxel 15 mg/m² once a week for a maximum of seven cycles. Investigators planned to enroll 600 patients but stopped the trial early when the survival benefit with docetaxel became evident.

Adding docetaxel improved 2-year disease-free survival (42% versus 30.3%; relative risk [HR]0.673; P = 0.002 ); Overall survival at 2 years (50.8% versus 41.7%; RR, 0.747; P = 0.035), and the locoregional failure rate at 2 years (41.8% versus 54.7%; HR, 0.661; P = .002).

The median overall survival was 25.5 months with docetaxel, compared to 15.3 months with radiotherapy alone (P = 0.035).

The benefits of docetaxel were most pronounced in patients with primary hypopharyngeal sites and in the 61% of definitively treated patients. There was “perhaps” a benefit in the adjuvant setting, but “further studies would be needed to show definitive applicability,” the researchers say.

There was a higher incidence of grade ≥3 mucositis (49.7% versus 22.2%), odynophagia (52.5% versus 33.5%) and dysphagia (33%), but the “complications were manageable and did not affect compliance” with radiation or docetaxel, the team reports. Overall, 86% of patients received five or more cycles of docetaxel.

In their editorial, Mell and Wong note that “the majority of patients did not receive intensity-modulated radiotherapy, the norm in high-income countries”, but add that “we do not expect the use of conventional radiotherapy reduces the effectiveness of docetaxel.”

The trial was funded by Tata Memorial Hospital, where it was conducted. Several researchers had ties to industry, including Patil, who reported research funding from Johnson & Johnson/Janssen, AstraZeneca, Intas, NATCO Pharma, Eisai Germany and Novartis. Mell is an advisor for Cel-Sci and has reported research funding from Merck and AstraZeneca. Wong disclosed research funding from Novartis and Merck.

J Clin Oncol. Published online December 9, 2022. Abstract, Editorial

Mr. Alexander Otto is a medical assistant with a Masters in Medical Science and a Journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism Fellow. E-mail: [email protected].

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