Feasibility of Pegylated Interferon in Children and Young Adults With Resected High‐Risk Melanoma

Abstract

Background Pegylated interferon α-2b (IFN α-2b) improves disease-free survival in adults with resected stage III melanoma. We conducted a study to determine the feasibility and safety of incorporating pegylated IFN α-2b as adjuvant therapy in the treatment of children and adolescents with high-risk melanoma. Pharmacokinetic studies of IFN α-2b and neuropsychological and quality of life (QOL) assessments were performed. Patient and Methods Eligible patients with resected AJCC Stage IIC, IIIA and IIIB cutaneous melanoma received non-pegylated IFN α-2b 20 million units/m2/day intravenously 5 days per week for 4 weeks (induction) followed by pegylated IFN α-2b 1 mcg/kg/dose weekly subcutaneously (SQ) for 48 weeks (maintenance). Results Twenty-three patients (15 females, median age 10 years) were enrolled. All patients completed induction therapy; whereas, 5 patients did not complete maintenance therapy either because of recurrent disease (n=2) or toxicity (n=3). The most common grade 3-4 toxicities of pegylated IFN α-2b were neutropenia (35%) and elevated liver transaminases (17%). The median non-pegylated IFN α-2b AUC0-∞ (5,026 pcg*hr/mL) was similar to adults. The median pegylated IFN α-2b exposure (48,480 pcg*hr/mL) was greater than the cumulative weekly exposure for non-pegylated IFN α-2b administered SQ three times per week (TIW). Validated measures demonstrated an improvement in QOL scores and no decline in psychological functioning over the course of therapy. Conclusions Pegylated IFN α-2b 1 mcg/kg/dose SQ weekly as maintenance therapy in children and adolescents with high-risk melanoma is feasible with tolerable toxicity and appears to yield higher exposures than non-pegylated IFN α-2b administered SQ TIW.

The role of routine imaging in pediatric cutaneous melanoma

“…We retrospectively reviewed the medical records of patients aged ≤21 years with AJCC stage IIC‐IV cutaneous MM treated on our institutional MEL06 protocol . Patients were referred for protocol enrollment after diagnosis of MM and were followed up through December 2017.…”

Cutaneous melanoma in adolescents and young adults

“…The use of SLNB for staging has become widespread, and primary tumors with a Breslow thickness > 0.75–1 mm and/or ulceration have been correlated with a higher incidence of nodal involvement . In the event of nodal disease (i.e., when SLNB is positive), it is worth considering complete lymph node dissection …”

“…Treatment options for young patients with high‐risk primary cutaneous melanoma (e.g., those with regional lymph node involvement) have always been limited. Treatment with adjuvant interferon (IFN) alpha‐2b has been revealed to have only a limited impact on oncological outcomes in this subset of patients . A valid alternative is still needed for patients at high risk of disease relapse.…”

“…44 In the event of nodal disease (i.e., when SLNB is positive), it is worth considering complete lymph node dissection. 24,45,46 Treatment options for young patients with high-risk primary cutaneous melanoma (e.g., those with regional lymph node involvement) have always been limited. Treatment with adjuvant interferon (IFN) alpha-2b has been revealed to have only a limited impact on oncological outcomes in this subset of patients.…”

“…Treatment with adjuvant interferon (IFN) alpha-2b has been revealed to have only a limited impact on oncological outcomes in this subset of patients. 39,45,46 A valid alternative is still needed for patients at high risk of disease relapse. Results from clinical trials in adult patients have shown that drugs currently in use for the treatment of metastatic disease can significantly improve survival rates when used in the adjuvant setting.…”