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Amifostine Provides Mucosal Protection in HNC Patients Treated With Chemoradiotherapy

Amifostine Provides Mucosal Protection in HNC Patients Treated With Chemoradiotherapy

MONTEGO BAY, JAMAICA- "Weekly carboplatin (Paraplatin) and paclitaxel (Taxol) given concurrently with definitive radiotherapy and daily amifostine (Ethyol) was well-tolerated by patients with advanced squamous cell head and neck cancers, and the cytoprotective agent amifostine appeared to decrease treatment-related toxicity," according to Mohan Suntharalingam, MD, vice chair of radiation oncology at the University of Maryland Greenebaum Cancer Center, Baltimore. Dr. Suntharalingam reported data from a prospective phase II trial evaluating the role of amifostine with this concurrent chemotherapy regimen at the 4th International Cytoprotection Investigators' Congress. Chemoradiation Doubles Toxicity "Few solid tumor sites have shown such good outcomes with combination radiation and chemotherapy as head and neck cancers, and combined-modality therapy is here to stay," Dr. Suntharalingam said. However, he noted that the regimens can result in a doubling of the rates of grade 3 or 4 mucosal toxicity, from about 24% with either chemotherapy or radiotherapy alone to about 43% with the combination. To address that problem, he and his colleagues conducted a prospective phase II trial to determine whether adding the cytoprotective agent amifostine could reduce mucosal toxicity without reducing tumor response. Dr. Suntharalingam reported data for 60 evaluable patients with unresectable stage III or IV squamous cell carcinomas of the head or neck. Patients were treated with daily radiation to the primary site up to 70.2 Gy (1.8 Gy/d) delivered with the shrinking field technique. Clinically involved nodes received the full dose, while uninvolved nodes received up to 50.4 Gy. Amifostine 500 mg IV was given less than 1 hour prior to radiotherapy. Concurrent weekly chemotherapy comprised of carboplatin 100 mg/m2 as a 30-minute infusion to AUC 1.5 and paclitaxel 40 mg/m2 IV as a 3-hour infusion. Majority Responded Dr. Suntharalingam reported that 82% of patients had complete responses (CR) at the primary site, and pathologic examination showed a CR rate of 73% in nodepositive patients. "Overall, 75% of patients had no evidence of disease following therapy," he said. Sixty percent of patients required treatment breaks, with a median duration of 1 day. Breaks were most often secondary to nausea/ vomiting (36%), dehydration (18%), dermatitis (11%), mucositis (5%), or neutropenia (5%). Most patients received all planned doses of amifostine. Three patients discontinued amifostine because of hypotension or nausea and vomiting. "It feels as if we are getting more therapy into these patients [with amifostine]," Dr. Suntharalingam said. He reported that the frequency of grade 3 xerostomia was 20% with amifostine, and noted that there was also only 20% grade 3 skin toxicity (no grade 4 toxicity). With regard to nonhematologic toxicities, patients who received amifostine seemed to experience toxicity later in the treatment period and require fewer treatment breaks, Dr. Suntharalingam said (see Figure 1). Leukopenia was somewhat higher with amifostine, but there was no decrease in efficacy. "Radiotherapy plus weekly carboplatin/ paclitaxel is a well-tolerated outpatient regimen with a complete response rate of 75% and an overall 5-year survival of 38%," Dr. Suntharalingam concluded. "Initial experience with the addition of amifostine suggests a benefit in terms of mucosal protection and xerostomia, while maintaining efficacy."

 
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