Abstract
BackgroundGlutamine (Gln) supplementation during concurrent chemoradiotherapy (C-CRT) effectively reduces the incidence and severity of acute radiation-induced esophagitis (RIE). However, there are concerns that Gln might stimulate tumor growth, and therefore negatively impact the outcomes of anticancer treatment. We retrospectively investigated the effect of co-administration of oral Gln during C-CRT on survival outcomes of patients with stage IIIB non-small cell lung carcinoma (NSCLC). We additionally evaluated role of oral Gln in preventing C-CRT-induced weight change, acute and late toxicities.MethodsThe study included 104 patients: 56 (53.8%) received prophylactic powdered Gln (Gln+) orally at a dose of 10 g/8 h and 48 (46.2%) did not receive Gln (Gln-) and served as controls. The prescribed radiation dose to the planning target volume was 66 Gy in 2-Gy fractions. Primary endpoints of progression-free survival (PFS), local/regional progression-free survival (LRPFS), and overall survival (OS) were correlated with status of Gln supplementation.ResultsOral Gln was well tolerated except for mild nausea/vomiting in 14 (25.0%) patients. There was no C-CRT-related acute or late grade 4–5 toxicity. Administration of Gln was associated with a decrease in the incidence of grade 3 acute radiation-induced esophagitis (RIE) (7.2% vs. 16.7% for Gln+ vs. Gln-; p=0.02) and late-RIE (0% vs. 6.3%; p=0.06), a reduced need for unplanned treatment breaks (7.1% vs. 20.8%; p=0.04), and reduced incidence of weight loss (44.6% vs. 72.9%; p=0.002). At a median follow-up of 24.2 months (range 9.2-34.4) the median OS, LRPFS, and PFS for Gln+ vs. Gln- cohorts were 21.4 vs. 20.4 (p=0.35), 14.2 vs.11.3 (p=0.16), and 10.2 vs. 9.0 months (p=0.11), respectively.ConclusionIn our study, supplementation with Gln during C-CRT had no detectable negative impact on tumor control and survival outcomes in patients with Stage IIIB NSCLC. Furthermore, Gln appeared to have a beneficial effect with respect to prevention of weight loss and unplanned treatment delays, and reduced the severity and incidence of acute- and late-RIE.
Highlights
Glutamine (Gln) supplementation during concurrent chemoradiotherapy (C-CRT) effectively reduces the incidence and severity of acute radiation-induced esophagitis (RIE)
Complications related to concurrent chemoradiotherapy (C-CRT) such as acute radiation-induced esophagitis (ARIE) may cause significant morbidity and unplanned treatment delays in patients with locally advanced nonsmall cell lung carcinoma (LA-non-small cell lung carcinoma (NSCLC))
Such complications impact the quality of life and reduce the ability to escalate the dose of radiotherapy (RT) to more effective levels, resulting in potential reductions in tumor control and survival rates
Summary
Glutamine (Gln) supplementation during concurrent chemoradiotherapy (C-CRT) effectively reduces the incidence and severity of acute radiation-induced esophagitis (RIE). Complications related to concurrent chemoradiotherapy (C-CRT) such as acute radiation-induced esophagitis (ARIE) may cause significant morbidity and unplanned treatment delays in patients with locally advanced nonsmall cell lung carcinoma (LA-NSCLC). Such complications impact the quality of life and reduce the ability to escalate the dose of radiotherapy (RT) to more effective levels, resulting in potential reductions in tumor control and survival rates. Gln is continuously provided by skeletal muscles during hypercatabolic states such as cancer, over time marked Gln depletion develops that cannot be overcome by increased synthesis [4] This results in compromised acid–base balance, immune functions, and epithelial integrity in the gut [5]. Two recent studies, including one from our institution, revealed a beneficial role of oral Gln in the reduction of ARIE incidence and severity, as well as maintenance of body weight, in LA-NSCLC patients treated with C-CRT [9,10]
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