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Title: Phase I trial of tirapazamine, cisplatin, and concurrent accelerated boost reirradiation in patients with recurrent head and neck cancer

Abstract

Purpose: Reirradiation (re-RT) with concurrent chemotherapy offers a therapeutic option in patients who have locoregional recurrence of head and neck cancer (HNC). The hypoxic cell sensitizer, tirapazamine (TPZ), has demonstrated promising results in first-line therapy for HNC. This phase I trial was designed to test the feasibility of giving TPZ in the re-RT setting. Methods and Materials: Patients with recurrent HNC who received prior radiotherapy (RT) were enrolled and received TPZ (260 mg/m{sup 2}) and cisplatin (50 mg/m{sup 2}) Weeks 1, 3, and 5 concurrently with RT (72 Gy, 42 fractions over 6 weeks). TPZ (160 mg/m{sup 2}) alone was added on Days 1, 3, and 5 of Week 2 (cohort 1) or Weeks 2 and 4 (cohort 2). Results: Twenty-five subjects were enrolled, 7 and 18 on cohorts 1 and 2, respectively. Significant toxicities included Grade 3 dermatitis (20%) and Grade 3 mucositis (40%). Dose-limiting toxicity was observed on cohort 2 (1 patient with aspiration pneumonia). Four deaths occurred during treatment. Two fatalities occurred after completing therapy as a result of carotid artery rupture. With a minimum and median follow-up of 14 and 24 months, respectively, median overall survival was 14 months with actuarial 1-year and 2-year survival ofmore » 56% and 27%, respectively. Conclusion: Reirradiation with concomitant chemotherapy including TPZ in patients with unresectable recurrent HNC is feasible and results in long-term survival in a significant proportion of patients.« less

Authors:
 [1];  [2];  [3];  [4];  [5];  [5];  [2];  [6];  [4];  [4];  [2]
  1. Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL (United States) and University of Chicago Cancer Research Center, Chicago, IL (United States). E-mail: ecohen@medicine.bsd.uchicago.edu
  2. Institut Gustave Roussy, Villejuif (France)
  3. University of Chicago Cancer Research Center, Chicago, IL (United States)
  4. (United States)
  5. Sanofi-Synthelabo Research, Malvern, PA (United States)
  6. Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL (United States)
Publication Date:
OSTI Identifier:
20944716
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.2006.09.056; PII: S0360-3016(06)03371-2; 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; CAROTID ARTERIES; CHEMOTHERAPY; DERMATITIS; HEAD; NECK; PATIENTS; PNEUMONIA; RADIATION DOSES; RADIOTHERAPY; RUPTURES; SENSITIZERS; TOXICITY

Citation Formats

Cohen, Ezra E.W., Rosine, Dominique, Haraf, Daniel J., Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, Loh, Elwyn, Shen, Liji, Lusinchi, Antoine, Vokes, Everett E., University of Chicago Cancer Research Center, Chicago, IL, Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, and Bourhis, Jean. Phase I trial of tirapazamine, cisplatin, and concurrent accelerated boost reirradiation in patients with recurrent head and neck cancer. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.09.056.
Cohen, Ezra E.W., Rosine, Dominique, Haraf, Daniel J., Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, Loh, Elwyn, Shen, Liji, Lusinchi, Antoine, Vokes, Everett E., University of Chicago Cancer Research Center, Chicago, IL, Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, & Bourhis, Jean. Phase I trial of tirapazamine, cisplatin, and concurrent accelerated boost reirradiation in patients with recurrent head and neck cancer. United States. doi:10.1016/j.ijrobp.2006.09.056.
Cohen, Ezra E.W., Rosine, Dominique, Haraf, Daniel J., Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, Loh, Elwyn, Shen, Liji, Lusinchi, Antoine, Vokes, Everett E., University of Chicago Cancer Research Center, Chicago, IL, Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, and Bourhis, Jean. Thu . "Phase I trial of tirapazamine, cisplatin, and concurrent accelerated boost reirradiation in patients with recurrent head and neck cancer". United States. doi:10.1016/j.ijrobp.2006.09.056.
@article{osti_20944716,
title = {Phase I trial of tirapazamine, cisplatin, and concurrent accelerated boost reirradiation in patients with recurrent head and neck cancer},
author = {Cohen, Ezra E.W. and Rosine, Dominique and Haraf, Daniel J. and Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL and Loh, Elwyn and Shen, Liji and Lusinchi, Antoine and Vokes, Everett E. and University of Chicago Cancer Research Center, Chicago, IL and Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL and Bourhis, Jean},
abstractNote = {Purpose: Reirradiation (re-RT) with concurrent chemotherapy offers a therapeutic option in patients who have locoregional recurrence of head and neck cancer (HNC). The hypoxic cell sensitizer, tirapazamine (TPZ), has demonstrated promising results in first-line therapy for HNC. This phase I trial was designed to test the feasibility of giving TPZ in the re-RT setting. Methods and Materials: Patients with recurrent HNC who received prior radiotherapy (RT) were enrolled and received TPZ (260 mg/m{sup 2}) and cisplatin (50 mg/m{sup 2}) Weeks 1, 3, and 5 concurrently with RT (72 Gy, 42 fractions over 6 weeks). TPZ (160 mg/m{sup 2}) alone was added on Days 1, 3, and 5 of Week 2 (cohort 1) or Weeks 2 and 4 (cohort 2). Results: Twenty-five subjects were enrolled, 7 and 18 on cohorts 1 and 2, respectively. Significant toxicities included Grade 3 dermatitis (20%) and Grade 3 mucositis (40%). Dose-limiting toxicity was observed on cohort 2 (1 patient with aspiration pneumonia). Four deaths occurred during treatment. Two fatalities occurred after completing therapy as a result of carotid artery rupture. With a minimum and median follow-up of 14 and 24 months, respectively, median overall survival was 14 months with actuarial 1-year and 2-year survival of 56% and 27%, respectively. Conclusion: Reirradiation with concomitant chemotherapy including TPZ in patients with unresectable recurrent HNC is feasible and results in long-term survival in a significant proportion of patients.},
doi = {10.1016/j.ijrobp.2006.09.056},
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: To present the first report of a Phase I trial evaluating concurrent and maintenance erlotinib and reirradiation in patients with recurrent or secondary primary head-and-neck cancer (HNC). Methods and Materials: Patients with recurrent or new primary HNC with an interval of at least 6 months since prior radiation were eligible. Patients were treated in 3 sequential cohorts: Cohort I, 100 mg of erlotinib daily with reirradiation at 61.6 Gy in 28 fractions; Cohort II, 150 mg of erlotinib with 61.6 Gy in 28 fractions; and Cohort III, 150 mg of erlotinib with 66 Gy in 30 fractions. Maintenance erlotinibmore » started immediately after reirradiation at 150 mg daily and was continued for 2 years or until disease progression or dose-limiting toxicity. Dose-limiting toxicities were defined as any Grade 4 or 5 toxicity or a toxicity-related delay in radiation therapy of greater than 7 days. Results: Fourteen patients were accrued, 3 to Cohort I, 4 to Cohort II, and 7 to Cohort III. Thirteen patients were evaluable for toxicity. Median follow-up was 8.4 months overall and 15.1 months for surviving patients. One patient had a dose-limiting toxicity in Cohort III. This patient declined initial percutaneous endoscopic gastrostomy tube placement, was hospitalized with Grade 3 dysphagia and aspiration, and required a delay in radiation therapy of greater than 7 days. No Grade 4 acute toxicity was observed. Acute Grade 3 toxicity occurred in 9 of 13 patients. No erlotinib-related toxicity of Grade 3 or greater was observed during maintenance therapy. One patient had Grade 5 carotid hemorrhage 6 months after reirradiation, and another patient had Grade 3 osteoradionecrosis. Conclusions: Reirradiation (66 Gy in 2.2 Gy fractions) with concurrent and maintenance erlotinib (150 mg daily) for recurrent or new primary HNC is feasible.« less
  • Purpose: Inoperable locoregional recurrences of head-and-neck cancer in a previously irradiated volume represent a therapeutic dilemma. Chemotherapy alone has no curative potential, whereas reirradiation and concurrent chemoradiation can salvage a small fraction of patients. Mucosal toxicity of concurrent chemoradiation requires substantial dose reduction of chemotherapy. Alternating chemoradiation offers the chance to give both full-dose chemotherapy and radiotherapy. The latter may provide a particular advantage for recurrent, potentially radiation resistant tumors. The feasibility and efficacy of a full-dose docetaxel containing alternating chemoradiation schedule was tested. Patients and Methods: Twenty-seven patients (Karnofsky performance status score {>=}70%) with histologically proven recurrent squamous cellmore » cancer that occurred {>=} 6 months in a previously irradiated area ({>=} 60 Gy) were considered unresectable and unsuitable for brachytherapy. Alternating chemoradiation consisted of 3 cycles of docetaxel 60 mg/m{sup 2} d1 and cisplatin 15 mg/m{sup 2} d2-5, q d22, and involved field radiotherapy 2.0 Gy every day d8-12, d15-19, d29-33, and d36-40 (40.0 Gy total dose). Dose reduction of docetaxel to 50 mg/m{sup 2} was necessary, because of hematologic toxicity in the first 12 patients. Results: Alternating chemoreirradiation was applied as planned in 12 of 27 patients, with reirradiation completed per protocol in 81%. Overall, patients received 83% of the intended dose of docetaxel and 73% of cisplatin. Third-degree common toxicity criteria mucositis occurred in 15%, leukopenia of {>=} third degree by common toxicity criteria in 37%, and 3 early deaths were observed. Median time to follow-up, time to local progression, median survival, and 3-year survival rates were 42 months, 10 months, 10 months, and 18%, respectively. Conclusions: Alternating chemoreirradiation in recurrences of head-and-neck cancer resulted in 80% overall response with acceptable toxicity. A significant minority of patients had durable tumor control with a chance of long-term survival.« less
  • Purpose: To report long-term results of randomized trial comparing 2 accelerated fractionations of definitive radiation therapy assessing the need to irradiate during weekend in patients with head and neck squamous cell carcinoma. Methods and Materials: A total of 345 patients with SCC of the oral cavity, larynx, and oro- or hypo-pharynx, stage T2-4N0-1M0, were randomized to receive continuous accelerated irradiation (CAIR: once per day, 7 days per week) or concomitant accelerated boost (CB: once per day, 3 days per week, and twice per day, 2 days per week). Total dose ranged from 66.6-72 Gy, dose per fraction was 1.8 Gy,more » number of fractions ranged from 37-40 fractions, and overall treatment time ranged from 37-40 days. Results: No differences for all trial end-points were noted. At 5 and 10 years, the actuarial rates of local-regional control were 63% and 60% for CAIR vs 65% and 60% for CB, and the corresponding overall survival were 40% and 25% vs 44% and 25%, respectively. Confluent mucositis was the main acute toxicity, with an incidence of 89% in CAIR and 86% in CB patients. The 5-year rate of grade 3-4 late radiation morbidity was 6% for both regimens. Conclusions: Results of this trial indicate that the effects of accelerated fractionation can be achieve by delivering twice-per-day irradiation on weekday(s). This trial has also confirmed that an accelerated, 6-weeks schedule is a reasonable option for patients with intermediate-stage head-and-neck squamous cell carcinoma because of the associated high cure rate and minimal severe late toxicity.« less
  • Purpose: The feasibility of combining concomitant boost-accelerated radiation regimen (AFX-C) with cisplatin was previously demonstrated in this Phase II trial. This article reports the long-term toxicity, relapse patterns, and survival in patients with advanced head and neck carcinoma. Methods and Materials: Between April and November 2000, 84 patients with Stage III-IV HNC were enrolled, and 76 patients were analyzable. Radiation consisted of 72 Gy over 6 weeks. Cisplatin dose was 100 mg/m{sup 2} on Days 1 and 22. Tumor and clinical status were assessed, and acute-late toxicities were graded. Results: The median follow-up for surviving patients is 4.3 years. Themore » 2- and 4-year locoregional failure rates were 33% and 36%, respectively, and the 2- and 4-year survival rates were 70% and 54%, respectively. The worst overall late Grade 3 or 4 toxicity rate was 42%. The prevalence rates of a gastrostomy at any time during follow-up, at 12 months, and at 48 months were 83%, 41%, and 17%, respectively. Five of 36 patients (14%) alive and without disease at last follow-up were gastrostomy-tube dependent. Conclusion: These data of long-term follow-up of patients treated with AFX-C with cisplatin show encouraging results with regard to locoregional disease control and survival, with few recurrences after 2 years. The late toxicity rates are relatively high. However, although prolonged dysphagia was noted in our preliminary report, its prevalence does decreased over time. A Phase III trial comparing AFX-C plus cisplatin against standard radiation plus cisplatin has completed accrual.« less
  • Purpose: Salvage options for unresectable locally recurrent, previously irradiated squamous cell carcinoma of the head and neck (rSCCHN) are limited. Although the addition of reirradiation may improve outcomes compared to chemotherapy alone, significant toxicities limit salvage reirradiation strategies, leading to suboptimal outcomes. We therefore designed a phase 2 protocol to evaluate the efficacy of stereotactic body radiation therapy (SBRT) plus cetuximab for rSCCHN. Methods and Materials: From July 2007 to March 2013, 50 patients >18 years of age with inoperable locoregionally confined rSCCHN within a previously irradiated field receiving ≥60 Gy, with a Zubrod performance status of 0 to 2, and normalmore » hepatic and renal function were enrolled. Patients received concurrent cetuximab (400 mg/m{sup 2} on day −7 and then 250 mg/m{sup 2} on days 0 and +8) plus SBRT (40-44 Gy in 5 fractions on alternating days over 1-2 weeks). Primary endpoints were 1-year locoregional progression-free survival and National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 graded toxicity. Results: Median follow-up for surviving patients was 18 months (range: 10-70). The 1-year local PFS rate was 60% (95% confidence interval [CI]: 44%-75%), locoregional PFS was 37% (95% CI: 23%-53%), distant PFS was 71% (95% CI: 54%-85%), and PFS was 33% (95% CI: 20%-49%). The median overall survival was 10 months (95% CI: 7-16), with a 1-year overall survival of 40% (95% CI: 26%-54%). At last follow-up, 69% died of disease, 4% died with disease, 15% died without progression, 10% were alive without progression, and 2% were alive with progression. Acute and late grade 3 toxicity was observed in 6% of patients respectively. Conclusions: SBRT with concurrent cetuximab appears to be a safe salvage treatment for rSCCHN of short overall treatment time.« less