PHILADELPHIA—For head and neck cancer patients, subcutaneous (SC) amifostine(Drug information on amifostine) (Ethyol) provides equal protection against radiation-induced grade 2 acute xerostomia compared to intravenous (IV) amifostine, Pramila Rani Anné, MD, reported. She cautioned, however, that SC amifostine should be used only in clinical trials until ways to prevent cutaneous toxicities are worked out.
Dr. Rani Anné, instructor in the Department of Radiation Oncology at Thomas Jefferson University Hospital in Philadelphia, presented phase II data comparing SC and IV amifostine in patients being treated with radiation therapy for head and neck cancer. The study followed trial WR-38, which showed that IV amifostine significantly reduced moderate-to-severe radiation-induced xerostomia in patients with head and neck cancer.
The SC formulation attracted attention after pharmacokinetic studies (WR-57) showed 50% dose-normalized bioavailability compared to IV dosing, with no reported nausea/vomiting or hypotension. The phase I comparison of IV, oral, and SC amifostine in a 3-way crossover study in 12 healthy volunteers showed similar plasma concentrations of WR-1065, the active metabolite of amifostine, apart from an early peak seen with the IV but not with the other regimens.
What’s Behind the Peak?
"This peak is thought to relate to hypotension and nausea. The question is whether it is also important for xerostomia protection," Dr. Rani Anné said.
Dr. Rani Anné’s phase II study with SC amifostine (WR-60) was undertaken in part to answer that question. The trial was designed to permit comparison with the previous study of IV amifostine (WR-38). "The primary study objective was to look at the effect of SC amifostine on incidence of grade 2 or worse acute xerostomia, assessed using the Radiation Therapy Oncology Group (RTOG) criteria," she said. Secondary objectives were effects on the incidence of grade 3 or worse acute mucositis, grade 2 or worse late xerostomia, and toxicity.
WR-60 enrolled 55 patients with newly diagnosed squamous cell head and neck cancer scheduled for radiotherapy to at least 40 Gy that would include at least 75% of both parotid glands. Patients could have no evidence of distant metastases and could not have had prophylactic pilocarpine(Drug information on pilocarpine).
