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- CancerConsultants (professional.cancerconsultants.com)
Researchers from Massachusetts General Hospital have reported that the dose of Taxol® (paclitaxel) given with hyperfractionated radiotherapy can be dose escalated in patients receiving Ethyol (amifostine). The details of this dose escalation trial were reported in the October 1, 2005, issue of Cancer .
Combined radiation therapy and chemotherapy are standard treatments for patients with advanced head and neck cancers, but most patients have recurrent disease after treatment. Ethyol is a radiation protector and the only drug of this class that has been approved by the FDA for this use in patients receiving radiation therapy for cancers of the head and neck.
Clinical trials have demonstrated that Ethyol can reduce both acute and late radiation-induced side effects. In the pivotal trial involving patients with head and neck cancer, Ethyol reduced the incidence of xerostomia but had no effect on the incidence or severity of oral mucositis. Ethyol has also been shown to reduce the incidence of grade 2-3 bladder and GI toxicities in patients receiving pelvic radiation therapy and more recently has been associated with decreased toxicities in patients receiving high-dose melphalan.
The current study was a multi-institution phase I clinical trial that included 36 patients with advanced head and neck cancer. Patients were treated with radiation therapy plus weekly Taxol. The number of doses of Taxol was escalated from a minimum of three to a maximum of six. Twenty-eight of these patients received Ethyol; eight received no Ethyol. Patients not receiving Ethyol tolerated four doses of Taxol while the average number of doses for the Ethyol group was five.
At approximately 30 months, both progression-free and overall survival was 66% in the whole group of patients. There were no differences in response rates between patients receiving and not receiving Ethyol.
These researchers concluded that Ethyol allows patients with advanced head and neck cancer who are also undergoing radiation therapy to tolerate an extra cycle of Taxol chemotherapy. Longer follow-up is necessary to determine if this will result in improved survival for these patients, and future randomized clinical trials are necessary to provide confirmed results.
Comments: Ethyol may increase the amount of Taxol that can be give concomitantly with radiotherapy, but the authors pointed out this is still not enough to significantly reduce distant relapses and more chemotherapy will have to be given before or after radiotherapy.
Amrein P, Clark J, Supko J, et al. Phase I trial and pharmacokinetics of escalating doses of paclitaxel and concurrent hyperfractionated radiotherapy with or without amifostine in patients with advanced head and neck carcinoma. Cancer . 2005;104:1418-1427.