Original article 223 Concurrent adjuvant radiotherapy and interferon-a2b for resected high risk stage III melanoma – a retrospective single centre study David E. Gyorki a , Jill Ainslie a , Michael Lim Joon a , Michael A. Henderson a , Michael Millward b and Grant A. McArthur a Interferon-a2b (IFNa2b) is the only form of systemic adjuvant therapy for stage III melanoma with documented survival benefit. Radiotherapy can also be utilized in the adjuvant setting in patients at high risk of nodal basin recurrence. As IFNa2b is associated with substantial toxicity, we sought to determine both the systemic and radiation-related toxicities in patients treated with combined adjuvant IFNa2b and regional adjuvant radiotherapy delivered in the setting of a single institution. Eighteen consecutive patients who commenced adjuvant IFNa2b between November 1997 and August 2002 were analysed retrospectively for toxicities associated with the combination of IFNa2b and adjuvant radiotherapy (40–50 Gy in 15–25 fractions) to nodal basins delivered during the maintenance phase of IFNa2b therapy (median dose during radiotherapy of 6.5 MU/m 2 three times per week). Seven out of 18 patients who received concurrent radiotherapy and IFNa2b displayed grade 3 skin reactions. Severe radiation-induced toxicity was seen in three further patients, one who developed radiation pneumonitis, one who developed severe oral mucositis, and one who developed wound dehiscence that took 10 months to resolve. Non-radiation-related toxicity to IFNa2b therapy was typical for this dose and schedule. We conclude that concurrent use of adjuvant radiotherapy and IFNa2b may enhance radiation-induced toxicity. However, overall we found concurrent radiation and IFNa2b could be safely delivered with appropriate clinical monitoring. Melanoma Res 14:223–230  c 2004 Lippincott Williams & Wilkins. Melanoma Research 2004, 14:223–230 Keywords: Melanoma, stage III, interferon-a2b, radiotherapy, lymph node metastases a Peter MacCallum Cancer Centre, Skin and Melanoma Service, St. Andrew’s Place, East Melbourne, Victoria, 3002, Australia and b Sir Charles Gardiner Hospital, Hospital Avenue Nedlands, Western Australia, 6009, Australia. Correspondence and requests for reprints to Dr Grant A. McArthur, Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, St Andrew’s Place, East Melbourne, Victoria, 3002, Australia. Tel: + 61 3 9656 1195; fax: + 61 3 9656 1408; e-mail: grant.mcarthur@petermac.org Received 29 September 2003 Accepted 13 February 2004 Introduction Melanoma is one of the most common cancers in Western countries such as the USA [1] and Australia [2]. Australia has one of the highest rates of melanoma in the world, with an estimated risk of one in 25 for men and one in 35 for women before the age of 75 years [2]. Over the last 30 years, the incidence has been increasing at a rate exceeding that for all other tumours [1,3]. The prognosis of patients with thick primary melanoma ( > 4 mm) or regional lymph node metastases remains poor, and effective adjuvant therapies are required [4]. Interferon-a2b (IFNa2b) has been shown to consistently have modest antitumour activity in metastatic melanoma. This led to the hypothesis that use of IFNa2b in the adjuvant setting may be of survival benefit in patients with thick primary melanoma or regional lymph node metastases. A variety of dosage regimens have been tested in clinical trials. The first trial of adjuvant interferon to show an increase in both disease-free and overall survival compared with observation was the Eastern Cooperative Oncology Group (ECOG) 1684 study reported by Kirkwood et al. [5]. The distinguishing feature of this regimen was a 4 week high dose induction phase. However, this dosage regimen was associated with significant levels of toxicity. Based on these data, the US Food and Drug Administration subsequently approved the use of IFNa2b for adjuvant treatment of high risk melanoma. Cole et al. [6], using the Q-TWIST analysis, subsequently performed a quality of life assessment and, despite the toxicity, postulated an overall advantage for IFNa2b use in terms of quality of life. The subsequent publication of the intergroup study E1690/S9111/C9190 [7] showed similar benefits on disease-free survival to those seen in ECOG 1684, but failed to show any overall survival benefit. It was possible that this was due to the use of IFNa2b as salvage therapy in the control arm, especially as 71% of patients with T4N0 thick primary melanomas did not receive an elective lymphadenectomy or sentinel lymph node sampling procedure. The results of this study, however, 0960-8931  c 2004 Lippincott Williams & Wilkins DOI: 10.1097/01.cmr.0000129375.14518.ab Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.