Treatment of advanced malignant melanoma with recombinant interferon alfa-2a in combination with DTIC: long-term follow-up of two phase II studies.
The present studies were designed to examine whether treatment of disseminated melanoma with a combination of recombinant interferon alpha (rIFN alpha-2a) and DTIC may provide better results than either agent alone. Two dose levels of rIFN alpha-2a were examined with the same dose and schedule of DTIC administration. In the first study 76 patients were treated with rIFN alpha-2a (3 x 10(6) IU days 1-3, 9 x 10(6) IU days 4-70 then 9 x 10(6) IU TIW) plus DTIC (i.v. 200 mg/m2, escalating to 800 mg/m2 each 21 d) for 6 months or longer or until failure. Responses were seen in 26% of patients overall (7CR, 13PR) with the highest responses being seen in those assessed as having a good prognosis and in patients with skin and/or lung metastases. It was notable that males showed a better response than females and that patients with metastases in lymph nodes showed low responses. Response rates in 30 patients treated with high-dose rIFN alpha-2a (18 x 10(6) IU days 7-70) were not superior to that seen at the lower dose and was accompanied by significant increase in bone marrow toxicity. The duration of responses appeared longer than expected from responses to DTIC alone and four patients remain progression free at periods in excess of 3 years. Failure in nine of the responders was due to the development of brain metastases which emphasizes the need for additional treatment approaches to treat micrometastases at this site. The results of a randomized control study comparing DTIC alone with DTIC plus 'low' dose rIFN alpha-2a are awaited with interest.
Newcastle Melanoma Unit, Wallsend District Hospital, New South Wales, Australia.
P
P
Hersey
G R
GR
McLeod
D B
DB
Thomson
D000293:Adolescent; D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011994:Recombinant Proteins
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D003606:Dacarbazine