title: Phase I study of pegylated interferon-alpha-2b as an adjuvant therapy in Japanese patients with malignant melanoma.
abstract: In the adjuvant setting for malignant melanoma, interferon (IFN)-α-2b and pegylated (PEG) IFN-α-2b were approved in several countries including the USA before these were approved in Japan. To resolve the "drug-lag" issue, this phase I study was designed to evaluate the safety and tolerability in Japanese patients with stage II or III malignant melanoma who had undergone surgery, by treating with PEG IFN-α-2b. As with a previously reported phase III study, patients were to receive PEG IFN-α-2b 6 μg/kg per week s.c. during an 8-week induction phase, followed by a maintenance phase at a dose of 3 μg/kg per week up to 5 years. Dose-limiting toxicity and pharmacokinetics were assessed during the initial 8 weeks. Of the nine patients enrolled, two patients had dose-limiting toxicities that resolved after discontinuation of treatment. The most frequently reported drug-related adverse events (DRAE) included pyrexia, decreased neutrophil and white blood cell counts, and arthralgia. Grade 3 DRAE included decreased neutrophil count. No deaths, serious adverse events and grade 4 adverse events were reported. Distant metastasis occurred in one patient. No apparent differences in area under the concentration-time curve and maximum observed serum concentration were observed between Japanese and historical non-Japanese pharmacokinetic data, suggesting no marked racial differences. No neutralizing antibody was detected in these patient samples. PEG IFN-α-2b was tolerated in Japanese patients, and eventually approved in Japan in May 2015 for adjuvant therapy in patients with stage III malignant melanoma. Because the number of patients was limited, further investigation would be crucial.
authors.affiliation: Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan. nyamazak@ncc.go.jp.
authors.forename: Naoya
authors.initials: N
authors.lastname: Yamazaki
authors.affiliation: Department of Dermatology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Uhara
authors.affiliation: Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Wada
authors.affiliation: Japan Development, MSD K.K., Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: Japan Development, MSD K.K., Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Japan Development, MSD K.K., Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimamoto
authors.affiliation: Dermatology Division, Shizuoka Cancer Center, Sunto-Gun, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kiyohara
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000328:Adult; D019540:Area Under Curve; D018771:Arthralgia / Q000276:immunology; D017024:Chemotherapy, Adjuvant; D005260:Female; D005334:Fever / Q000276:immunology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007564:Japan; D007958:Leukocyte Count; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000601:surgery; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology; D011092:Polyethylene Glycols / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000601:surgery; D055815:Young Adult; D000096142:Cutaneous Malignant Melanoma
chemical_list: D000276:Adjuvants, Immunologic; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b
keywords: Japanese; adjuvant therapy; melanoma; peg-interferon α-2b; phase I