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Title: A Phase II trial of subcutaneous amifostine and radiation therapy in patients with head-and-neck cancer

Abstract

Purpose: Intravenous amifostine 200 mg/m{sup 2} reduces xerostomia in head-and-neck cancer patients. This Phase II study evaluated subcutaneous (s.c.) amifostine in a similar patient population. Patients and Methods: Patients received amifostine 500 mg, administered as two 250-mg s.c. injections 60 min before once-daily radiation for head-and-neck cancer (50-70 Gy in 5-7 weeks). The primary endpoint was the incidence of {>=}Grade 2 acute xerostomia. Results: Fifty-four patients received s.c. amifostine and radiotherapy. The incidence of {>=}Grade 2 acute xerostomia was 56% (95% CI, 43-69%) and the incidence of {>=}Grade 2 late xerostomia at 1 year was 45% (95% CI, 29-61%). The incidence of acute xerostomia was lower than reported previously with no amifostine in a controlled study; rates of acute xerostomia were similar between s.c. and i.v. amifostine in the two studies. The rate of late xerostomia with s.c. amifostine was intermediate between rates for i.v. amifostine and no amifostine, and not statistically significantly different from either historical control. Grades 1-2 nausea and emesis were the most common amifostine-related adverse events. Grade 3 amifostine-related adverse events reported by >1 patient included: dehydration (11%); rash (6%); and weight decrease, mucositis, dyspnea, and allergic reaction (each 4%). Seven patients (13%) had serious cutaneousmore » adverse events outside the injection site. One-year rates of locoregional control, progression-free survival, and overall survival were 78%, 75%, and 85%, respectively. Conclusions: Subcutaneous amifostine provides a well-tolerated yet simpler alternative to i.v. amifostine for reducing acute xerostomia in head-and-neck cancer patients.« less

Authors:
 [1];  [2];  [3];  [4];  [3];  [5];  [6];  [7];  [8];  [9]
  1. Thomas Jefferson University Hospital, Bodine Center for Cancer Research, Philadelphia, PA (United States). E-mail: rani.anne@mail.tju.edu
  2. Department of Radiation Oncology, Hospital of University of Pennsylvania, Philadelphia, PA (United States)
  3. University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)
  4. Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)
  5. Alta Bates Comprehensive Cancer Center, Berkeley, CA (United States)
  6. Rhode Island Hospital, Providence, RI (United States)
  7. Comprehensive Cancer Institute, Huntsville, AL (United States)
  8. St. Vincent's Cancer Center, New York, NY (United States)
  9. Thomas Jefferson University Hospital, Bodine Center for Cancer Research, Philadelphia, PA (United States)
Publication Date:
OSTI Identifier:
20944686
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 67; Journal Issue: 2; Other Information: DOI: 10.1016/j.ijrobp.2006.08.044; PII: S0360-3016(06)02810-0; 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; CARCINOMAS; DEHYDRATION; HEAD; NAUSEA; NECK; PATIENTS; RADIOTHERAPY

Citation Formats

Anne, Pramila Rani, Machtay, Mitchell, Rosenthal, David I., Brizel, David M., Morrison, William H., Irwin, David H., Chougule, Prakash B., Estopinal, Noel C., Berson, Anthony, and Curran, Walter J.. A Phase II trial of subcutaneous amifostine and radiation therapy in patients with head-and-neck cancer. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.08.044.
Anne, Pramila Rani, Machtay, Mitchell, Rosenthal, David I., Brizel, David M., Morrison, William H., Irwin, David H., Chougule, Prakash B., Estopinal, Noel C., Berson, Anthony, & Curran, Walter J.. A Phase II trial of subcutaneous amifostine and radiation therapy in patients with head-and-neck cancer. United States. doi:10.1016/j.ijrobp.2006.08.044.
Anne, Pramila Rani, Machtay, Mitchell, Rosenthal, David I., Brizel, David M., Morrison, William H., Irwin, David H., Chougule, Prakash B., Estopinal, Noel C., Berson, Anthony, and Curran, Walter J.. Thu . "A Phase II trial of subcutaneous amifostine and radiation therapy in patients with head-and-neck cancer". United States. doi:10.1016/j.ijrobp.2006.08.044.
@article{osti_20944686,
title = {A Phase II trial of subcutaneous amifostine and radiation therapy in patients with head-and-neck cancer},
author = {Anne, Pramila Rani and Machtay, Mitchell and Rosenthal, David I. and Brizel, David M. and Morrison, William H. and Irwin, David H. and Chougule, Prakash B. and Estopinal, Noel C. and Berson, Anthony and Curran, Walter J.},
abstractNote = {Purpose: Intravenous amifostine 200 mg/m{sup 2} reduces xerostomia in head-and-neck cancer patients. This Phase II study evaluated subcutaneous (s.c.) amifostine in a similar patient population. Patients and Methods: Patients received amifostine 500 mg, administered as two 250-mg s.c. injections 60 min before once-daily radiation for head-and-neck cancer (50-70 Gy in 5-7 weeks). The primary endpoint was the incidence of {>=}Grade 2 acute xerostomia. Results: Fifty-four patients received s.c. amifostine and radiotherapy. The incidence of {>=}Grade 2 acute xerostomia was 56% (95% CI, 43-69%) and the incidence of {>=}Grade 2 late xerostomia at 1 year was 45% (95% CI, 29-61%). The incidence of acute xerostomia was lower than reported previously with no amifostine in a controlled study; rates of acute xerostomia were similar between s.c. and i.v. amifostine in the two studies. The rate of late xerostomia with s.c. amifostine was intermediate between rates for i.v. amifostine and no amifostine, and not statistically significantly different from either historical control. Grades 1-2 nausea and emesis were the most common amifostine-related adverse events. Grade 3 amifostine-related adverse events reported by >1 patient included: dehydration (11%); rash (6%); and weight decrease, mucositis, dyspnea, and allergic reaction (each 4%). Seven patients (13%) had serious cutaneous adverse events outside the injection site. One-year rates of locoregional control, progression-free survival, and overall survival were 78%, 75%, and 85%, respectively. Conclusions: Subcutaneous amifostine provides a well-tolerated yet simpler alternative to i.v. amifostine for reducing acute xerostomia in head-and-neck cancer patients.},
doi = {10.1016/j.ijrobp.2006.08.044},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 67,
place = {United States},
year = {Thu Feb 01 00:00:00 EST 2007},
month = {Thu Feb 01 00:00:00 EST 2007}
}
  • Purpose: To report long-term data from a prospective trial of subcutaneous (s.c.) amifostine in patients who received chemoradiotherapy for squamous cell carcinoma of the head and neck (SCCHN). Methods and Materials: Patients {>=}18 years of age with previously untreated Stage III/IV SCCHN received fractionated radiotherapy, 1.8-2.0 Gy/day, 5 days per week, to a total dose of 70-72 Gy, plus weekly paclitaxel (40 mg/m{sup 2}) and carboplatin (100 mg/m{sup 2}) administered intravenously (i.v.) for 6 weeks. All patients received 500 mg s.c. amifostine 30-60 min before radiotherapy with antihistamine and antiemetic prophylaxis. Results: Twenty patients were evaluable (median age, 55 years).more » The incidence of Grade 2 xerostomia was 42% and 29% at 12 and 18 months, respectively; there were no reports of Grade {>=}3 xerostomia. Grade {>=}3 mucositis occurred in 30% of patients, with median time to resolution of 12.5 weeks (range, 5-17 weeks). Survival estimates at 1 and 2 years were 95% and 71%, respectively. All patients experienced Grade 2 weight loss; 7 patients (35%) experienced Grade {<=}2 nausea/vomiting. There were no reports of Grade {>=}3 amifostine-related adverse events. Conclusions: Subcutaneous amifostine was well tolerated by patients receiving chemoradiotherapy for SCCHN, with lower rates of nausea/vomiting than reported in trials with i.v. amifostine. Xerostomia and mucositis rates were similar to those reported in trials with i.v. amifostine.« less
  • Purpose: To investigate a novel chemoradiation regimen designed to maximize locoregional control (LRC) and minimize toxicity for patients with advanced head-and-neck squamous cell carcinoma (HNSCC). Methods and Materials: Patients received hyperfractionated intensity modulated radiation therapy (HIMRT) in 1.25-Gy fractions b.i.d. to 70 Gy to high-risk planning target volume (PTV). Intermediate and low-risk PTVs received 60 Gy and 50 Gy, at 1.07, and 0.89 Gy per fraction, respectively. Concurrent cisplatin 33 mg/m{sup 2}/week was started Week 1. Patients completed the Quality of Life Radiation Therapy Instrument pretreatment (PRE), at end of treatment (EOT), and at 1, 3, 6, 9, and 12more » months. Overall survival (OS), progression-free (PFS), LRC, and toxicities were assessed. Results: Of 39 patients, 30 (77%) were alive without disease at median follow-up of 37.5 months. Actuarial 3-year OS, PFS, and LRC were 80%, 82%, and 87%, respectively. No failures occurred in the electively irradiated neck and there were no isolated neck failures. Head and neck QOL was significantly worse in 18 of 35 patients (51%): mean 7.8 PRE vs. 3.9 EOT. By month 1, H and N QOL returned near baseline (mean 6.2, SD = 1.7). The most common acute Grade 3+ toxicities were mucositis (38%), fatigue (28%), dysphagia (28%), and leukopenia (26%). Conclusions: Hyperfractionated IMRT with low-dose weekly cisplatin resulted in good LRC with acceptable toxicity and QOL. Lack of elective nodal failures despite very low dose per fraction has led to an attempt to further minimize toxicity by reducing elective nodal doses in our subsequent protocol.« less
  • 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: To evaluate chronic xerostomia and tumor control 18 and 24 months after initial treatment with amifostine in a randomized controlled trial of patients with head-and-neck cancer; at 12 months after radiotherapy (RT), amifostine had been shown to reduce xerostomia without changing tumor control. Methods and Materials: Adults with head-and-neck cancer who underwent once-daily RT for 5-7 weeks (total dose, 50-70 Gy) received either open-label amifostine (200 mg/m{sup 2} i.v.) 15-30 min before each fraction of radiation (n = 150) or RT alone (control; n = 153). Results: Amifostine administration was associated with a reduced incidence of Grade {>=}2 xerostomiamore » over 2 years of follow-up (p = 0.002), an increase in the proportion of patients with meaningful (>0.1 g) unstimulated saliva production at 24 months (p = 0.011), and reduced mouth dryness scores on a patient benefit questionnaire at 24 months (p < 0.001). Locoregional control rate, progression-free survival, and overall survival were not significantly different between the amifostine group and the control group. Conclusions: Amifostine administration during head-and-neck RT reduces the severity and duration of xerostomia 2 years after treatment and does not seem to compromise locoregional control rates, progression-free survival, or overall survival.« less
  • Purpose: This paper reports long-term results of RTOG 9903, to determine whether the addition of erythropoietin (EPO) would improve the outcomes of radiation therapy (RT) in mildly to moderately anemic patients with head and neck squamous cell carcinoma (HNSCCa). Methods and Materials: The trial included HNSCCa patients treated with definitive RT. Patients with stage III or IV disease received concomitant chemoradiation therapy or accelerated fractionation. Pretreatment hemoglobin levels were required to be between 9.0 and 13.5 g/dL (12.5 g/dL for females). EPO, 40,000 U, was administered weekly starting 7 to 10 days before RT was initiated in the RT + EPO arm. Results: A total ofmore » 141 of 148 enrolled patients were evaluable. The baseline median hemoglobin level was 12.1 g/dL. In the RT + EPO arm, the mean hemoglobin level at 4 weeks increased by 1.66 g/dL, whereas it decreased by 0.24 g/dL in the RT arm. With a median follow-up of 7.95 years (range: 1.66-10.08 years) for surviving patients and 3.33 years for all patients (range: 0.03-10.08 years), the 5-year estimate of local-regional failure was 46.2% versus 39.4% (P=.42), local-regional progression-free survival was 31.5% versus 37.6% (P=.20), and overall survival was 36.9% versus 38.2% (P=.54) for the RT + EPO and RT arms, respectively. Late toxicity was not different between the 2 arms. Conclusions: This long-term analysis confirmed that despite the ability of EPO to raise hemoglobin levels in anemic patients with HNSCCa, it did not improve outcomes when added to RT. The possibility of a detrimental effect of EPO could not be ruled out.« less