Subcutaneous (SbQ) Versus Intravenous (IV) Administration of Amifostine for Head and Neck (HN) Cancer Patients Receiving Radiotherapy (RT): Preliminary Results of the GORTEC 2000-02 Randomized Trial

Reviewer: Charles Wood, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 19, 2005

Presenter: E. Bardet
Presenter's Affiliation: Crlcc, Nantes, France
Type of Session: Scientific

Background

There are several advantages offered by SbQ amifostine over IV amifostine including easier administration and a favorable window between drug injection and radiation delivery. This trial tested the hypothesis that SbQ amifostine was associated with an improved toxicity profile with regards to late xerostomia versus IV amifostine.

Materials and Methods

311 patients with biopsy-proven HN carcinoma to be treated with external beam radiation in the definitive or postoperative setting with >75% of the bilateral parotid glands within the radiation field were randomized between 3/01 and 1/05 to receive SbQ versus IV amifostine
Patients received daily amifostine, either 500 mg/m2 SbQ in 2 injections 20 to 60 minutes prior to radiation or 200 mg/m2 via a 3 minute IV infusion 15 to 30 minutes prior to radiation
Radiation was delivered per conventional technique to a minimum dose of 50 Gy for microscopic disease and 70 Gy for gross disease, all via 2 Gy daily fractions
Acute and late xerostomia was assessed via salivary flow measurement, RTOG scoring, and a Patient Benefit Questionnaire

Results

Median follow-up for 285 patients (145 SbQ and 140 IV) with available data was 15 months
The study arms were well-balanced with respect to sex, age, performance status, histologic type, tumor location, and stage
There was no statistical difference in Grade 2-3 acute radiation toxicity between the study arms

	SbQ	IV	p
Mucositis	80%	80%	NS
Skin	67%	72%	NS
Xerostomia	40%	39%	NS

There was no statistical difference in Grade 2-3 acute amifostine administration toxicity between the study arms

	SbQ	IV	p
Nausea	14%	16%	NS
Asthenia	3%	2%	NS
Hypotension	1%	3%	NS
Local Pain	9%	0%	0.0008
Fever	0%	2%	0.07
Rash	22%	11%	0.02

94% versus 97% (SbQ versus IV) received the full radiation dose, and 71% versus 70% (SbQ versus IV) received the full amifostine dose
There was no statistical difference in mean stimulated salivary flow between the study arms
There was no statistical difference in Patient Benefit Questionnaire Results between the study arms
There was no statistical difference in either overall survival or locoregional control between the study arms

Author's Conclusions

SbQ amifostine may be a more practical alternative to IV amifostine with a similar toxicity profile
Preliminary data suggests that late xerostomia is not different between the study arms

Clinical/Scientific Implications

In this preliminary analysis of GORTEC 2000-2002, the toxicity profiles of subcutaneous and intravenous amifostine appeared relatively similar. Subcutaneous administration is certainly a more attractive option from a logistical standpoint, as it entails less time and effort and provides a longer window between drug delivery and radiation treatment. However, this study involved a rather heterogeneous population of head and neck cancer patients, including patients treated with definitive radiation alone, chemoradiation alone, and postoperative radiation; generalization of results to each subgroup is unclear. Furthermore, IMRT was not utilized in this study and could very well influence the toxicity profiles. It will be interesting to await maturation of the data so that outcome with respect to overall survival and locoregional control can be evaluated with adequate follow-up.