Influence of oral glutamine supplementation on survival outcomes of patients treated with concurrent chemoradiotherapy for locally advanced non-small cell lung cancer

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.

Altered Glutamine Metabolism and Therapeutic Opportunities for Lung Cancer

“…Contrary to expectations, the possible deleterious effect of glutamine on therapeutic efficacy, given its role in tumor biology, did not materialize, with comparable median overall survival and progression free survival of 21.4 vs. 20.4 (p=0.35) and 10.2 vs. 9.0 months (p=0.11) in glutamine-treated and untreated patient groups respectively. 96 A possible explanation for the preserved treatment efficacy with glutamine supplementation could be the retrospective nature of the studies since a modest effect may be too small for small retrospective studies to demonstrate. Additionally, whether the glutamine supplementation was sufficient to induce any meaningful alterations in the biologic behavior of glutamine-dependent tumors is unknown.…”

Oral Glutamine in Preventing Treatment‐Related Mucositis in Adult Patients With Cancer

“…An overview of the included studies is presented in Table 1. The cancer type was different in various studies: 4 studies in lung cancer, 7,[19][20][21] 3 in breast cancer, 5,22,23 3 in head and neck cancer, [24][25][26] 1 with GI cancers, 27 1 with hematologic malignancies, 28 1 with multiple solid tumors, 29 1 with various types of cancers, 30 and 1 study without a defined cancer type. 31 Ten articles were prospective, 5,21,[23][24][25][27][28][29][30][31] and 5 were retrospective studies.…”

“…31 Ten articles were prospective, 5,21,[23][24][25][27][28][29][30][31] and 5 were retrospective studies. 7,19,20,22,26 Anticancer treatment modality included chemotherapy only, 5,22,23,27,[29][30][31] radiation only, 19,24,28 and their combination. 7,20,21,25,26 Ten studies evaluated oral mucositis (stomatitis) only, 5,[22][23][24][25][27][28][29][30][31] 4 studied esophageal mucositis only, 7,[19][20][21] and 1 evaluated both.…”

“…7,19,20,22,26 Anticancer treatment modality included chemotherapy only, 5,22,23,27,[29][30][31] radiation only, 19,24,28 and their combination. 7,20,21,25,26 Ten studies evaluated oral mucositis (stomatitis) only, 5,[22][23][24][25][27][28][29][30][31] 4 studied esophageal mucositis only, 7,[19][20][21] and 1 evaluated both. 26 Three of the trials were designed as crossover studies, 5,27,30 while the remaining 12 used a parallel group design.…”

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“…20 vs. 9 Wochen [295]) und dass nach 1 Jahr noch 10 -30 % der PEG-Patienten über die Sonde ernährt wurden [298]. Parallel berichten 2 Gruppen über eine höhere Inzidenz von Dysphagie bei PEG-Patienten [292,296,299] [303]. Der orale Einsatz von Glutamin zur Linderung einer durch Bestrahlung der Beckenregion induzierten Enteritis zeigte in 4 randomisiert kontrollierten Studien [304 -307] in einem Fall eine Verringerung des Enteritisschweregrads [307], in einer Studie eine Steigerung der Enteritisinzidenz [306] und in den beiden anderen Untersuchungen keinen Effekt [304,305].…”