Costs of treatment intensification for head and neck cancer: Concomitant chemoradiation randomised for radioprotection with amifostine

Abstract

This study presents an overview of costs of a chemoradiation protocol in head and neck cancer patients and an analysis of whether prevention of acute toxicity with amifostine results in a reduction to costs. Fifty-four patients treated with weekly paclitaxel concomitant with radiation were randomised for treatment with subcutaneously administered amifostine (500 mg) and analysed with respect to costs of treatment. Total costs for work-up, treatment and toxicity were calculated per treatment arm.

No significant differences were found between treatment arms in preliminary results regarding response (98%), toxicity and 2-year survival (77%). Average costs for toxicity were € 3.789, largely influenced by hospital admissions (€ 3.013). Total costs for amifostine administration amounted to € 6.495 per patient. The average total costs of treatment were € 19.647 versus € 13.592 with or without amifostine, respectively.

The applied (subcutaneous) dose of amifostine appeared to be insufficient for radioprotection and reduction of related costs in the concomitant chemoradiation scheme, whereas total costs increased remarkably. Although it would be accompanied by a further cost raise, applying a higher amifostine dose might reduce (mucosal) toxicity and therefore in the long run lower related costs for hospital admission and tube feeding.

Introduction

Current treatment strategies for advanced stage head and neck cancer (H&NC) aim at increasing survival and (locoregional) tumour control with organ function preservation by implementing multi-modality treatment schedules and altered fractionation schemes. Examples of such approaches include a combination of concurrently applied chemotherapy and radiotherapy [1]; reduction of overall treatment time and/or increase of total applied radiation dose 2, 3; and in some cases followed by a neck dissection [4]. A drawback however is the increased rate of acute toxicity 3, 5. Ways to overcome this (mainly mucosal) toxicity are being explored. For instance, the use of radioprotectors such as amifostine (Ethyol^®, MedImmune Oncology, Gaithersburg, MD) might reduce acute mucositis 6, 7 and acute and late xerostomia [8] after (chemo-) radiotherapy.

In an attempt to increase tumour control probability, as of year 2000, at the Erasmus MC in Rotterdam, The Netherlands, all patients with a malignancy in the head and neck region are treated with a slightly accelerated fractionation schedule, i.e. 6 fractions of 2 Gy per week. Additionally, selected tumours of the tonsillar fossa, soft palate and base of tongue are boosted using interstitial brachytherapy. Brachytherapy has the advantage of a high tumour dose in a short overall treatment time (e.g. 20 Gy in 4–6 days), without compromising the surrounding normal tissues [9].

In April 2000 a randomised clinical trial for the treatment of stage (II), III and IVa [10] squamous cell carcinoma of the head and neck (nasopharyngeal carcinoma and N3-disease excluded) was initiated [11]. The chemotherapy agent was paclitaxel (Taxol^®, Bristol-Meyers Squibb, Princeton, NJ). Paclitaxel was applied concurrently with external beam radiation. Patients were randomised for radioprotection with amifostine or no radioprotection.

This clinical study focused on the radioprotective effect of amifostine on major salivary glands and mucosal linings (xerostomia, acute mucositis) after subcutaneous (sc) administration. Taking bioavailability into account subcutaneous administration of amifostine is believed to be as effective as intravenous (iv) administration [12], and moreover, to be less toxic (no allergic reactions, hypotension, nausea or vomiting) [13]. Therefor a reduction of workload and related costs as compared to iv administration can be achieved administering amifostine sc.

During the past decade, costs for radiotherapy (in H&NC) have increased due to the implementation of 3D-conformal radiotherapy (3DCRT), intensity modulated radiation techniques (IMRT), brachytherapy, stereotactic RT and combination with chemotherapy [14]. Amifostine treatment is known to be costly. Apart from the costs for medication, chemoradiation increases the rate, severity and duration of acute mucosal toxicity and dysphagia 5, 11, 15, 16. More patients are being admitted to the hospital due to dehydration, malnutrition and weight loss and therefore become dependent on (gastrostomy catheters for) tube feeding. Complex IMRT plans increase the labor intensity of the treatment planning procedure as well as the treatment delivery time and need for quality assurance [17].

The primary objective of this paper was to compare actual costs of treatment between the two treatment arms of our study, in order to investigate whether the increased costs of chemoradiation would be compensated by a reduction in acute toxicity and related expenses, using amifostine. The secondary objective was to present a detailed overview of (expected) costs of a concomitant chemoradiation treatment protocol in H&NC patients.