PHILADELPHIAFor head and neck cancer patients, subcutaneous (SC)
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.