A new randomized, placebo-controlled, double-blind clinical trial has investigated the effects of oral L-glutamine supplementation on survival outcomes in patients with locally advanced head and neck cancer receiving chemoradiotherapy. The study was conducted at Osaka University Hospital in Japan and published in the journal Nutrients on September 23, 2023.
The primary purpose of this study was to examine whether L-glutamine supplementation influences overall survival and progression-free survival in head and neck cancer patients undergoing intensive chemoradiotherapy. This follows previous research by the same group showing that glutamine can reduce the severity of treatment-induced mucositis in these patients.
A total of 40 patients with locally advanced head and neck squamous cell carcinoma were initially enrolled in the trial between May 2010 and June 2013. After excluding two patients with nasopharyngeal cancer, 38 patients were ultimately included in the analysis - 20 in the glutamine group and 18 in the placebo group. To be eligible, patients had to have stage III or IV disease and be scheduled to receive definitive chemoradiotherapy.
The study population consisted predominantly of men (33 out of 38 patients), with a mean age of 60.5 years in the glutamine group and 64.1 years in the placebo group. Patients were matched between groups for primary tumor site, tumor stage, body mass index, and performance status.
All patients received radiation therapy to a total dose of 66 or 70 Gy, delivered in 2 Gy daily fractions over 6-7 weeks. Concurrent chemotherapy consisted of weekly intravenous cisplatin (20 mg/m2) and docetaxel (10 mg/m2) for 6 weeks. The glutamine group received 10 g of oral L-glutamine powder three times daily throughout the course of chemoradiotherapy, while the placebo group received an identical-appearing placebo powder.
The primary endpoints were overall survival and progression-free survival at 5 years follow-up. At this time point, 16 out of 20 patients (80%) in the glutamine group and 13 out of 18 patients (72%) in the placebo group had survived. The mean overall survival was 55.2 months for the glutamine group versus 48.3 months for the placebo group, with no statistically significant difference between groups (p=0.583).
For progression-free survival, 14 out of 20 patients (70%) in the glutamine group and 12 out of 18 patients (67%) in the placebo group remained free of disease progression at 5 years. Mean progression-free survival was 46.7 months for glutamine versus 43.6 months for placebo, again with no significant difference (p=0.682).
The authors concluded that oral L-glutamine supplementation during chemoradiotherapy does not appear to negatively impact survival outcomes in patients with locally advanced head and neck cancer. This finding is reassuring, as there have been theoretical concerns that glutamine supplementation could potentially stimulate tumor growth or interfere with the efficacy of cancer treatments.
However, the study does have some important limitations that should be considered. The sample size was relatively small at only 38 patients, which limits statistical power to detect small differences between groups. The study was also conducted at a single center in Japan, so the results may not be fully generalizable to other populations. Additionally, only one dosing regimen of glutamine was tested (30 g per day), so the effects of other doses remain unknown.
Despite these limitations, this trial provides valuable long-term survival data on the use of glutamine in head and neck cancer patients receiving definitive chemoradiotherapy. The results suggest that glutamine can likely be safely administered to reduce treatment-related mucositis without compromising oncologic outcomes. However, larger multi-center trials would be beneficial to confirm these findings.
The potential clinical impact of this research is significant, as reducing the toxicity of chemoradiotherapy without affecting its efficacy could allow more patients to complete their prescribed treatment course. This in turn may lead to improved disease control and survival. The ability to safely administer glutamine could also improve quality of life for patients undergoing this intensive cancer therapy.
Moving forward, additional research is still needed to optimize glutamine supplementation protocols and to investigate its effects in other cancer types and treatment regimens. Studies examining the underlying mechanisms by which glutamine protects normal tissues without stimulating tumor growth would also be valuable. For now, this study provides important reassurance about the safety of glutamine use in head and neck cancer patients receiving chemoradiotherapy.
It's worth noting that this trial was investigator-initiated and does not appear to have been funded by any pharmaceutical or nutritional supplement company, enhancing its credibility. The use of a randomized, double-blind, placebo-controlled design also strengthens the reliability of the results. While further research is still needed, this study represents an important contribution to the ongoing investigation of supportive care strategies in cancer treatment.
References
Tsujimoto T, Wasa M, Inohara H, Ito T. L-Glutamine and Survival of Patients with Locally Advanced Head and Neck Cancer Receiving Chemoradiotherapy. Nutrients. 2023;15(19):4117. Published 2023 Sep 23. doi:10.3390/nu15194117
