Phase II study of temozolomide plus pegylated interferon-alpha-2b for metastatic melanoma.
BACKGROUND
Temozolomide and interferon-alpha-2b (IFN-alpha-2b) are both active in melanoma. Therefore, the efficacy and safety of temozolomide in combination with pegylated IFN-alpha-2b in patients with metastatic melanoma without brain metastases was investigated.


METHODS
Patients with histologically confirmed, unresectable, American Joint Committee on Cancer Stage IV melanoma were enrolled in an open-label, Phase II study. The primary endpoints were tumor response and safety. Patients received temozolomide (75 mg/m2/dayx6 weeks with a 2-week break between cycles) plus concomitant subcutaneous pegylated IFN-alpha-2b (0.5 microg/kg/wk, continuously). Treatment was continued until unacceptable toxicity or disease progression occurred.


RESULTS
Thirty-five patients (median age, 55 years) with Stage IV melanoma and a median of 3 metastatic sites were enrolled and received a median of 1 cycle (i.e., 8 weeks) of therapy (range, 0-6 cycles). Eleven patients (31%) (95% confidence interval, 16% to 47%) had an objective tumor response, including 3 with clinical complete response durations of 6 months, 20 months, and 32+ months and 8 with partial responses. Three patients with a partial or mixed response were subsequently rendered free of clinically detectable disease with surgery. The median survival was 12 months with a median follow-up among survivors of 16 months. No patient developed brain metastases while receiving study treatment. Treatment was generally well tolerated. Hematologic toxicity consisted mainly of lymphopenia and leukopenia (National Cancer Institute Common Toxicity Criteria Grades 1-3); no Grade 4 hematologic toxicity was observed.


CONCLUSIONS
The combination of temozolomide plus pegylated IFN-alpha-2b had antitumor activity and was well tolerated in patients with metastatic melanoma. Therefore, further study is warranted.
Hwu
Wen-Jen
WJ
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. wenjhwu@mdanderson.org
Panageas
Katherine S
KS
Menell
Jennifer H
JH
Lamb
Lynne A
LA
Aird
Suzan
S
Krown
Susan E
SE
Williams
Linda J
LJ
Chapman
Paul B
PB
Livingston
Philip O
PO
Wolchok
Jedd D
JD
Houghton
Alan N
AN
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005134:Eye Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012074:Remission Induction; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D000077204:Temozolomide
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D003606:Dacarbazine; C417083:peginterferon alfa-2b; D000077204:Temozolomide