Combined treatment with pegylated interferon-alpha-2a and dacarbazine in patients with advanced metastatic melanoma: a phase 2 study.
BACKGROUND
Dacarbazine (DTIC) and pegylated interferon (IFN)-alpha-2a have both demonstrated some efficacy as single agents in metastatic melanoma. To the authors' knowledge, the current study is the first to test a combination of these 2 agents in a phase 2 trial.


METHODS
Twenty-eight patients with stage IV melanoma without brain metastases were treated with DTIC (at a dose of 850 mg/m(2) every 3 weeks) combined with weekly pegylated IFN-alpha-2a at a dose of 180 microg. The study was initiated to evaluate the efficacy and tolerability of the combination. The primary study endpoint was objective response.


RESULTS
Twenty-five patients were evaluable for response. Two patients (8.0%) achieved a complete response that continued for >480 days and 746 days, respectively. Four patients (16.0%) demonstrated a partial response, and another patient experienced stable disease. Six of 7 nonprogressive patients had either not received treatment or had not developed disease progression during adjuvant IFN treatment for stage II/III disease. The median duration of response was 236 days, the median progression-free survival was 56 days, and the overall survival time was 403 days. Few grade 3 toxicities and only 1 grade 4 toxicity were observed (according to National Cancer Institute Common Toxicity Criteria).


CONCLUSIONS
The combination of DTIC and pegylated IFN-alpha-2a was found to be well tolerated in patients with metastatic melanoma. The response rate of 24%, including 2 long-lasting complete responses, is encouraging, but must be confirmed in larger trials.
Hauschild
Axel
A
Department of Dermatology, University of Schleswig-Holstein, Campus Kiel, Kiel, Germany. ahauschild@dermatology.uni-kiel.de
Dummer
Reinhard
R
Ugurel
Selma
S
Kaehler
Katharina C
KC
Egberts
Friederike
F
Fink
Wolfram
W
Both-Skalsky
Jeannine
J
Laetsch
Barbara
B
Schadendorf
Dirk
D
D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D003606:Dacarbazine / Q000627:therapeutic use*; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011379:Prognosis; D011446:Prospective Studies; D011994:Recombinant Proteins; D015996:Survival Rate
D018906:Antineoplastic Agents, Alkylating; D000998:Antiviral Agents; D004337:Drug Carriers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D003606:Dacarbazine; C100416:peginterferon alfa-2a