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Title: The impact of concurrent granulocyte macrophage-colony stimulating factor on radiation-induced mucositis in head and neck cancer patients: A double-blind placebo-controlled prospective Phase III study by Radiation Therapy Oncology Group 9901

Abstract

Purpose: Based on early clinical evidence of potential mucosal protection by granulocyte-macrophage colony stimulating factor (GM-CSF), the Radiation Therapy Oncology Group conducted a double-blind, placebo-controlled, randomized study to test the efficacy and safety of GM-CSF in reducing the severity and duration of mucosal injury and pain (mucositis) associated with curative radiotherapy (RT) in head-and-neck cancer patients. Methods and Materials: Eligible patients included those with head-and-neck cancer with radiation ports encompassing >50% of oral cavity and/or oropharynx. Standard RT ports were used to cover the primary tumor and regional lymphatics at risk in standard fractionation to 60-70 Gy. Concurrent cisplatin chemotherapy was allowed. Patients were randomized to receive subcutaneous injection of GM-CSF 250 {mu}g/m{sup 2} or placebo 3 times a week. Mucosal reaction was assessed during the course of RT using the National Cancer Institute Common Toxicity Criteria and the protocol-specific scoring system. Results: Between October 2000 and September 2002, 130 patients from 36 institutions were accrued. Nine patients (7%) were excluded from the analysis, 3 as a result of drug unavailability. More than 80% of the patients participated in the quality-of-life endpoint of this study. The GM-CSF did not cause any increase in toxicity compared with placebo. There was nomore » statistically significant difference in the average mean mucositis score in the GM-CSF and placebo arms by a t test (p = 0.4006). Conclusion: This placebo-controlled, randomized study demonstrated no significant effect of GM-CSF given concurrently compared with placebo in reducing the severity or duration of RT-induced mucositis in patients undergoing definitive RT for head-and-neck cancer.« less

Authors:
 [1];  [2];  [3];  [4];  [5];  [6];  [7];  [8];  [9];  [10]
  1. Department of Radiation Oncology, University of California, Davis Medical Center, Sacramento, CA (United States). E-mail: janice.ryu@ucdmc.ucdavis.edu
  2. Department of Statistics, Radiation Therapy Oncology Group, Philadelphia, PA (United States)
  3. Oral Oncology Department, Harper Hospital/Wayne State University, Detroit, MI (United States)
  4. Rex Healthcare Cancer Center, Raleigh, NC (United States)
  5. Division of Geriatric Oncology, University of South Florida H. Lee Moffitt Cancer Center, Tampa, FL (United States)
  6. Department of Radiation Oncology, University of California, Davis Medical Center, Sacramento, CA (United States)
  7. Department of Radiation Therapy/Oncology L'Hotel-Dieu de Quebec, Notre Dame Hospital, Quebec City, Quebec (Canada)
  8. Department of Radiation Oncology, Shiffler Cancer Center, Wheeling Hospital, Wheeling, WV (United States)
  9. Department of Radiation Oncology, Wayne State University, Detroit, MI (United States)
  10. Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States)
Publication Date:
OSTI Identifier:
20944712
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 67; Journal Issue: 3; Other Information: DOI: 10.1016/j.ijrobp.2006.09.043; PII: S0360-3016(06)03225-1; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CHEMOTHERAPY; FRACTIONATED IRRADIATION; HEAD; INJURIES; LEUKOCYTES; MACROPHAGES; NECK; NEOPLASMS; ORAL CAVITY; PAIN; PATIENTS; RADIOTHERAPY; SAFETY STANDARDS; SUBCUTANEOUS INJECTION; TOXICITY

Citation Formats

Ryu, Janice K., Swann, Suzanne, LeVeque, Francis, Scarantino, Charles W., Johnson, Darlene J., Chen, Allan, Fortin, Andre, Pollock, JonDavid, Kim, Harold, and Ang, Kian K. The impact of concurrent granulocyte macrophage-colony stimulating factor on radiation-induced mucositis in head and neck cancer patients: A double-blind placebo-controlled prospective Phase III study by Radiation Therapy Oncology Group 9901. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.09.043.
Ryu, Janice K., Swann, Suzanne, LeVeque, Francis, Scarantino, Charles W., Johnson, Darlene J., Chen, Allan, Fortin, Andre, Pollock, JonDavid, Kim, Harold, & Ang, Kian K. The impact of concurrent granulocyte macrophage-colony stimulating factor on radiation-induced mucositis in head and neck cancer patients: A double-blind placebo-controlled prospective Phase III study by Radiation Therapy Oncology Group 9901. United States. doi:10.1016/j.ijrobp.2006.09.043.
Ryu, Janice K., Swann, Suzanne, LeVeque, Francis, Scarantino, Charles W., Johnson, Darlene J., Chen, Allan, Fortin, Andre, Pollock, JonDavid, Kim, Harold, and Ang, Kian K. Thu . "The impact of concurrent granulocyte macrophage-colony stimulating factor on radiation-induced mucositis in head and neck cancer patients: A double-blind placebo-controlled prospective Phase III study by Radiation Therapy Oncology Group 9901". United States. doi:10.1016/j.ijrobp.2006.09.043.
@article{osti_20944712,
title = {The impact of concurrent granulocyte macrophage-colony stimulating factor on radiation-induced mucositis in head and neck cancer patients: A double-blind placebo-controlled prospective Phase III study by Radiation Therapy Oncology Group 9901},
author = {Ryu, Janice K. and Swann, Suzanne and LeVeque, Francis and Scarantino, Charles W. and Johnson, Darlene J. and Chen, Allan and Fortin, Andre and Pollock, JonDavid and Kim, Harold and Ang, Kian K.},
abstractNote = {Purpose: Based on early clinical evidence of potential mucosal protection by granulocyte-macrophage colony stimulating factor (GM-CSF), the Radiation Therapy Oncology Group conducted a double-blind, placebo-controlled, randomized study to test the efficacy and safety of GM-CSF in reducing the severity and duration of mucosal injury and pain (mucositis) associated with curative radiotherapy (RT) in head-and-neck cancer patients. Methods and Materials: Eligible patients included those with head-and-neck cancer with radiation ports encompassing >50% of oral cavity and/or oropharynx. Standard RT ports were used to cover the primary tumor and regional lymphatics at risk in standard fractionation to 60-70 Gy. Concurrent cisplatin chemotherapy was allowed. Patients were randomized to receive subcutaneous injection of GM-CSF 250 {mu}g/m{sup 2} or placebo 3 times a week. Mucosal reaction was assessed during the course of RT using the National Cancer Institute Common Toxicity Criteria and the protocol-specific scoring system. Results: Between October 2000 and September 2002, 130 patients from 36 institutions were accrued. Nine patients (7%) were excluded from the analysis, 3 as a result of drug unavailability. More than 80% of the patients participated in the quality-of-life endpoint of this study. The GM-CSF did not cause any increase in toxicity compared with placebo. There was no statistically significant difference in the average mean mucositis score in the GM-CSF and placebo arms by a t test (p = 0.4006). Conclusion: This placebo-controlled, randomized study demonstrated no significant effect of GM-CSF given concurrently compared with placebo in reducing the severity or duration of RT-induced mucositis in patients undergoing definitive RT for head-and-neck cancer.},
doi = {10.1016/j.ijrobp.2006.09.043},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 3,
volume = 67,
place = {United States},
year = {Thu Mar 01 00:00:00 EST 2007},
month = {Thu Mar 01 00:00:00 EST 2007}
}
  • Purpose: Taste alterations (dysgeusia) are well described in head and neck cancer patients who undergo radiotherapy (RT). Anecdotal observations and pilot studies have suggested zinc may mitigate these symptoms. This multi-institutional, double-blind, placebo-controlled trial was conducted to provide definitive evidence of this mineral's palliative efficacy. Methods and Materials: A total of 169 evaluable patients were randomly assigned to zinc sulfate 45 mg orally three times daily vs. placebo. Treatment was to be given throughout RT and for 1 month after. All patients were scheduled to receive {>=}2,000 cGy of external beam RT to {>=}30% of the oral cavity, were ablemore » to take oral medication, and had no oral thrush at study entry. Changes in taste were assessed using the previously validated Wickham questionnaire. Results: At baseline, the groups were comparable in age, gender, and planned radiation dose (<6,000 vs. {>=}6,000 cGy). Overall, 61 zinc-treated (73%) and 71 placebo-exposed (84%) patients described taste alterations during the first 2 months (p = 0.16). The median interval to taste alterations was 2.3 vs. 1.6 weeks in the zinc-treated and placebo-exposed patients, respectively (p = 0.09). The reported taste alterations included the absence of any taste (16%), bitter taste (8%), salty taste (5%), sour taste (4%), sweet taste (5%), and the presence of a metallic taste (10%), as well as other descriptions provided by a write in response (81%). Zinc sulfate did not favorably affect the interval to taste recovery. Conclusion: Zinc sulfate, as prescribed in this trial, did not prevent taste alterations in cancer patients who were undergoing RT to the oral pharynx.« less
  • Purpose: The quality of life (QOL) and neurocognitive function of patients with brain tumors are negatively affected by the symptoms of their disease and brain radiation therapy (RT). We assessed the effect of prophylactic d-threo-methylphenidate HCl (d-MPH), a central nervous system (CNS) stimulant on QOL and cognitive function in patients undergoing RT. Methods and Materials: Sixty-eight patients with primary or metastatic brain tumors were randomly assigned to receive d-MPH or placebo. The starting dose of d-MPH was 5 mg twice daily (b.i.d.) and was escalated by 5 mg b.i.d. to a maximum of 15 mg b.i.d. The placebo was administeredmore » as one pill b.i.d. escalating three pills b.i.d. The primary outcome was fatigue. Patients were assessed at baseline, the end of radiation therapy, and 4, 8, and 12 weeks after brain RT using the Functional Assessment of Cancer Therapy with brain and fatigue (FACIT-F) subscales, as well as the Center for Epidemiologic Studies Scale and Mini-Mental Status Exam. Results: The Mean Fatigue Subscale Score at baseline was 34.7 for the d-MPH arm and 33.3 for the placebo arm (p = 0.61). At 8 weeks after the completion of brain RT, there was no difference in fatigue between patient groups. The adjusted least squares estimate of the Mean Fatigue Subscale Score was 33.7 for the d-MPH and 35.6 for the placebo arm (p = 0.64). Secondary outcomes were not different between the two treatment arms. Conclusions: Prophylactic use of d-MPH in brain tumor patients undergoing RT did not result in an improvement in QOL.« less
  • Purpose: Oral mucositis is a major complication of concurrent chemoradiotherapy (CRT) in head-and-neck cancer patients. Low-level laser (LLL) therapy is a promising preventive therapy. We aimed to evaluate the efficacy of LLL therapy to decrease severe oral mucositis and its effect on RT interruptions. Methods and Materials: In the present randomized, double-blind, Phase III study, patients received either gallium-aluminum-arsenide LLL therapy 2.5 J/cm{sup 2} or placebo laser, before each radiation fraction. Eligible patients had to have been diagnosed with squamous cell carcinoma or undifferentiated carcinoma of the oral cavity, pharynx, larynx, or metastases to the neck with an unknown primarymore » site. They were treated with adjuvant or definitive CRT, consisting of conventional RT 60-70 Gy (range, 1.8-2.0 Gy/d, 5 times/wk) and concurrent cisplatin. The primary endpoints were the oral mucositis severity in Weeks 2, 4, and 6 and the number of RT interruptions because of mucositis. The secondary endpoints included patient-reported pain scores. To detect a decrease in the incidence of Grade 3 or 4 oral mucositis from 80% to 50%, we planned to enroll 74 patients. Results: A total of 75 patients were included, and 37 patients received preventive LLL therapy. The mean delivered radiation dose was greater in the patients treated with LLL (69.4 vs. 67.9 Gy, p = .03). During CRT, the number of patients diagnosed with Grade 3 or 4 oral mucositis treated with LLL vs. placebo was 4 vs. 5 (Week 2, p = 1.0), 4 vs. 12 (Week 4, p = .08), and 8 vs. 9 (Week 6, p = 1.0), respectively. More of the patients treated with placebo had RT interruptions because of mucositis (6 vs. 0, p = .02). No difference was detected between the treatment arms in the incidence of severe pain. Conclusions: LLL therapy was not effective in reducing severe oral mucositis, although a marginal benefit could not be excluded. It reduced RT interruptions in these head-and-neck cancer patients, which might translate into improved CRT efficacy.« less
  • Purpose: Acute radiation proctitis is the most relevant complication of pelvic radiation and is still mainly treated supportively. Considering the negative impact of acute proctitis symptoms on patients' daily activities and the potential relationship between the severity of acute radiation injury and late damage, misoprostol was tested in the prevention of acute radiation-induced proctitis. Methods and Materials: A total of 100 patients who underwent radiotherapy for prostate cancer were entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. Radiation-induced toxicity was evaluated weekly during radiotherapy using the Common Toxicity Criteria. Results: Between the placebo andmore » the misoprostol groups, no significant differences in proctitis symptoms occurred: 76% of patients in each group had Grade 1 toxicity, and 26% in the placebo group and 36% in the misoprostol group had Grade 2 toxicity. No differences were found in onset or symptom duration. Comparing the peak incidence of patients' toxicity symptoms, significantly more patients experienced rectal bleeding in the misoprostol group (p = 0.03). Conclusion: Misoprostol given as a once-daily suppository did not decrease the incidence and severity of radiation-induced acute proctitis and may increase the incidence of acute bleeding.« less
  • Purpose: We performed this double-blinded, placebo-controlled study to determine the safety and efficacy of L-alanyl-L-glutamine in the prevention of mucositis in patients with head-and-neck cancer. Methods and Materials: Thirty-two patients with head-and-neck cancer were treated with chemoradiotherapy (CRT) (radiotherapy daily up to 70 Gy plus cisplatin/5-fluoruracil once a week) and were asked to participate. Twenty-nine patients received the CRT schedule and were double-blindly assigned to receive either intravenous L-alanyl-L-glutamine 0.4 g/kg weight/day or an equal volume of saline (placebo) during chemotherapy days. Results: Fourteen patients received L-alanyl-L-glutamine and 15 received placebo. Mucositis was assessed by the Objective Mucositis Score (OMS)more » and the World Health Organization (WHO) grading system. There was a significant difference in incidence of mucositis developed in patients receiving placebo compared with those who received L-alanyl-L-glutamine (p = 0.035). The number of patients with severe objective mucositis (OMS >1.49) was higher in the placebo group compared with the L-alanyl-L-glutamine group (67% vs. 14%, p 0.007). L-alanyl-L-glutamine patients experienced less pain (three highest Numeric Rating Scale scores of 1.3/10 vs. 6.3/10 respectively, p = 0.008) and need for feeding tubes (14% vs. 60% respectively, p = 0.020) compared with placebo patients. No adverse effects related to the drug or the infusions were noted in either group. Conclusion: For patients with head-and-neck cancer receiving CRT, intravenous L-alanyl-L-glutamine may be an effective preventive measure to decrease the severity of mucositis.« less