Randomized Phase 3, Double-Blind, Placebo-Controlled Study of Prophylactic Gabapentin for the Reduction of Oral Mucositis Pain During the Treatment of Oropharyngeal Squamous Cell Carcinoma

Cook, Andrew; Modh, Ankit; Ali, Haythem; Sheqwara, Jawad; Chang, Steven S.; Ghanem, Tamer; Momin, Suhael; Wu, Vivian; Tam, Samantha; Money, Sarah; Han, Xiaodong; Fakhoury, Lamis; Movsas, Benjamin; Siddiqui, Farzan

doi:10.1016/j.ijrobp.2021.11.012

Cited by 11 publications

(7 citation statements)

References 41 publications

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“…Prophylactic use of 3600 mg gabapentin was well tolerated, halved the overall opioid use, and significantly delayed the time to first opioid use for OM pain management during RT while maintaining similar patient-reported OM soreness scores. Consistent with our study, Smith et al found that gabapentin decreased pain during RT; however, they were unable to escalate most patients beyond 900 mg, while 86% of patients without contraindications for gabapentin tolerated escalation to 3600 mg in our study [ 5 ]. A prospective randomized trial examining the addition of venlafaxine to 3600 mg gabapentin found no improvement in pain control or quality of life but similarly demonstrated that more than 90% of patients in the trial tolerated high-dose gabapentin through to the conclusion of treatment [ 13 ].…”

Section: Discussionsupporting

confidence: 89%

“…In the treatment of HNSCC, Ma et al prospectively showed that escalating doses of gabapentin (900, 2700, and 3600 mg) were well tolerated, effective in reducing opiate use during RT, and did not worsen the need for a feeding tube (FT) [ 4 ]. In contrast, other prospective trials have found that patients could not escalate gabapentin beyond 900 mg [ 5 ], there was no pain benefit with 1800 mg of gabapentin, and patients on gabapentin had a significantly higher rate of FT placement [ 6 ]. Consequently, the tolerability, benefits, and feeding tube rate of dose-escalated gabapentin remain controversial.…”

Section: Introductionmentioning

confidence: 99%

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Prophylactic High-Dose Gabapentin Reduces Opiate Use during Radiation Therapy for Head and Neck Squamous Cell Carcinoma

Qiu¹,

Iovoli

Khan³

et al. 2023

Cancers

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Background: The role of prophylactic high-dose gabapentin for the management of oral mucositis during radiation therapy for head and neck squamous cell carcinoma (HNSCC) remains controversial. Methods: A retrospective cohort analysis was performed on primary HNSCC patients treated at our institution. Kruskal–Wallis and Fisher’s exact tests were used to compare the patients’ baseline characteristics. Multivariate competing risk and logistic regressions were performed to evaluate time to first opioid use and feeding tube placement. Results: In total, 480 consecutive HNSCC patients were included. Within this cohort, 186 patients received 3600 mg gabapentin, 182 received 300 to 3200 mg gabapentin, and 112 received no gabapentin. The time to first opioid use was greater in the 3600 mg group compared with the no gabapentin group (34.3 vs. 23.9 days, p < 0.001) and to the 300 to 3200 mg group (28.0 days, p < 0.001). The proportion of patients requiring opioids at any point during RT was lower in the 3600 mg gabapentin group compared with the no gabapentin group (31.8% vs. 60.1%, p < 0.001) and with the 300 to 3200 mg group (63.8%, p < 0.001). Conclusions: Prophylactic use of 3600 mg gabapentin was well tolerated, halved overall opioid use, and delayed the time to first opioid use during radiation therapy.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Prophylactic High-Dose Gabapentin Reduces Opiate Use during Radiation Therapy for Head and Neck Squamous Cell Carcinoma

Qiu¹,

Iovoli

Khan³

et al. 2023

Cancers

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“…This study is, to our knowledge, the first evaluation of prospective data to suggest that higher doses of gabapentin (900-3600 mg daily) are well tolerated and associated with delayed time to first opioid use for OM pain control. Consistent with our study, Smith et al found that gabapentin decreased pain during RT, but the dose was not increased beyond 900 mg for most patients because early pain relief occurred at this dose; most patients in our study tolerated 3600 mg. Cook et al found no benefit to using 1800 mg of gabapentin daily; patients receiving gabapentin had a higher rate of FT placement than patients receiving placebo (62.1% vs 20.7%). In our study, FT placement rates were comparable between subgroups of the 3600 mg and 900 mg cohorts in which methadone was used for rescue treatment, whereas the rate was significantly worse in the subgroup of the 2700 mg cohort in which hydrocodone and fentanyl were used for rescue treatment.…”

Section: Discussionmentioning

confidence: 99%

“…opioid use for OM pain control. Consistent with our study, Smith et al 5 found that gabapentin decreased pain during RT, but the dose was not increased beyond 900 mg for most patients because early pain relief occurred at this dose; most patients in our study tolerated 3600 mg. Cook et al 6 found no benefit to using 1800 mg of gabapentin daily; patients receiving gabapentin had a higher rate of FT placement than patients receiving placebo (62.1% vs 20.7%). In our study, FT placement rates were comparable between subgroups of the 3600 mg and 900 mg cohorts in which Multivariable competing risks analysis among cohorts receiving daily doses of gabapentin, 900 mg, 2700 mg, or 3600 mg (reference cohort).…”

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confidence: 99%

Association of Gabapentin Use With Pain Control and Feeding Tube Placement Among Patients With Head and Neck Cancer Receiving Chemoradiotherapy

et al. 2022

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Almost one-half of patients treated with radiotherapy (RT) for oropharyngeal cancer require chronic opioid use to manage oral mucositis (OM) pain. 1 Given the paucity of level 1 evidence for OM pain management, current guidelines allow consideration of prophylactic gabapentin. 2,3 However, the optimal dose remains unclear. In this comparative effectiveness study, we performed a secondary analysis of 2 clinical trials conducted by this research team, hypothesizing that a higher dose of gabapentin would be associated with less opioid use and feeding tube (FT) placement. MethodsEligible patients in both studies received concurrent chemoradiotherapy for nonmetastatic squamous cell carcinoma of the head and neck and prophylactic oral gabapentin (titrated to 900 mg vs 2700 mg daily in 1 study 4 and 3600 mg daily in the other study). Using the 3600 mg cohort as the reference group, we performed a multivariable competing risks analysis to evaluate time to first use of opioids and a logistic regression analysis to assess FT placement, adjusted for baseline characteristics. This study followed the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) reporting guideline. Additional information is available in eMethods in the Supplement. ResultsAmong 92 patients, the median age was 62.1 years (IQR, 55.4-66.4 years); 82 patients were male (89.1%), and 10 (10.9%) were female. Baseline cohort characteristics were well balanced (Table ).Most patients tolerated gabapentin per protocol. For example, adverse effects from gabapentin, such as dizziness and drowsiness, were only reported in 1 patient (3.1%) in the 3600 mg cohort (grade 3 dizziness) and 2 patients (6.3%) in the 3600 mg cohort (gabapentin was discontinued because of nausea and vomiting partly associated with RT and low adherence to oral hygiene).The multivariable competing risks model revealed the time to first opioid use for additional pain control was greatest in the 3600 mg cohort (Figure). The proportion of patients requiring opioids during RT was also smallest in the 3600 mg cohort (12 patients [37.5%]) vs the 900 mg cohort (27 patients [93.1%]) and the 2700 mg cohort (19 patients [61.3%]; P < .001). Multivariable logistic regression analysis revealed that, compared with the 3600 mg cohort (3 patients [9.4%]), the 2700 mg cohort (14 patients [45.2%]) had significantly greater odds of FT placement during RT (adjusted odds ratio, 9.9; 95% CI, 2.1-75.7; P = .009); however, the odds were not significantly greater in the 900 mg cohort (6 patients [20.7%]; adjusted odds ratio, 3.6; 95% CI, 0.7-28.1; P = .15). DiscussionThis study is, to our knowledge, the first evaluation of prospective data to suggest that higher doses of gabapentin (900-3600 mg daily) are well tolerated and associated with delayed time to first

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“…To the editor: We would like to sincerely thank Drs Smith and Murphy for their careful and critical evaluation 1 of our recently published double-masked, randomized, placebocontrolled trial regarding the role of prophylactic gabapentin in alleviating mucositis-related pain in patients receiving radiation therapy for oropharyngeal cancers. 2 They have conducted a detailed statistical analysis to conclude that approximately 190 patients, randomized between 2 treatment arms, would be required to prove or disprove the role of gabapentin. As per their evaluation, the 60 patients in our study are inadequate to conclude that this is a "negative" trial.…”

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confidence: 99%

In Reply to Smith et al.

Siddiqui

Cook

2022

International Journal of Radiation Oncology*Biology*Physics

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Randomized Phase 3, Double-Blind, Placebo-Controlled Study of Prophylactic Gabapentin for the Reduction of Oral Mucositis Pain During the Treatment of Oropharyngeal Squamous Cell Carcinoma

Cited by 11 publications

References 41 publications

Prophylactic High-Dose Gabapentin Reduces Opiate Use during Radiation Therapy for Head and Neck Squamous Cell Carcinoma

Prophylactic High-Dose Gabapentin Reduces Opiate Use during Radiation Therapy for Head and Neck Squamous Cell Carcinoma

Association of Gabapentin Use With Pain Control and Feeding Tube Placement Among Patients With Head and Neck Cancer Receiving Chemoradiotherapy

In Reply to Smith et al.

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