Concurrent adjuvant radiotherapy and interferon-α2b for resected high risk stage III melanoma – a retrospective single centre study

Abstract

Interferon-alpha2b (IFNalpha2b) 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 IFNalpha2b is associated with substantial toxicity, we sought to determine both the systemic and radiation-related toxicities in patients treated with combined adjuvant IFNalpha2b and regional adjuvant radiotherapy delivered in the setting of a single institution. Eighteen consecutive patients who commenced adjuvant IFNalpha2b between November 1997 and August 2002 were analysed retrospectively for toxicities associated with the combination of IFNalpha2b and adjuvant radiotherapy (40-50 Gy in 15-25 fractions) to nodal basins delivered during the maintenance phase of IFNalpha2b therapy (median dose during radiotherapy of 6.5 MU/m three times per week). Seven out of 18 patients who received concurrent radiotherapy and IFNalpha2b 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 IFNalpha2b therapy was typical for this dose and schedule. We conclude that concurrent use of adjuvant radiotherapy and IFNalpha2b may enhance radiation-induced toxicity. However, overall we found concurrent radiation and IFNalpha2b could be safely delivered with appropriate clinical monitoring.

The Florida Melanoma Trial I: A Prospective Multicenter Phase I/II Trial of Postoperative Hypofractionated Adjuvant Radiotherapy with Concurrent Interferon-Alfa-2b in the Treatment of Advanced Stage III Melanoma with Long-Term Toxicity Follow-Up

“…A summary of these studies is described in Table 8. Several small retrospective studies have recently been reported on the role of concurrent radiotherapy or interferon or radiotherapy within 1 month of the delivery of interferon in resected high-risk melanoma [22][23][24][25]. These studies have generally reported locoregional control rates to be comparable with historical rates (Table 9).…”

Toxicity of combined treatment of adjuvant irradiation and interferon α2b in high-risk melanoma patients

“…Gyorki et al [29] report a group of patients (n = 18) who were treated concurrently with radiotherapy and IFNa2b, with a total dose of radiation ranging from 40-50 Gy and fractionation of 200-300 cGy; they found 50% grade III acute toxicities occurring in 44.4% of patients and grade III late toxicities in two patients, observing a correlation of acute/late toxicity with higher total dose of radiation (50 Gy). Nguyen et al [30] observed grade III acute toxicity (mucositis-dermatitis) at total radiation doses of 45, 41.4 and 59.4 Gy and 180 cGy doses per fraction respectively, in a subset of three patients with melanoma of the head and neck region, treated with concurrent radiation and IFNa2b.…”

Loco-regional control after postoperative radiotherapy for patients with regional nodal metastases from melanoma

“…The potential role of a radiosensitising effect of IFN and subsequent subacute or late toxicities when administered concurrently [17,[32][33][34], independently of the fraction size, has been previously described. Currently, the optimal sequence of radiation and IFN therapy is unknown.…”