Isotretinoin and recombinant interferon alfa-2a therapy of metastatic malignant melanoma.
Twenty-five patients with metastatic malignant melanoma were treated with isotretinoin (13-cis-retinoic acid) orally at 1 mg/kg daily and recombinant interferon alfa-2a (INF-alpha) subcutaneously at 3 million units daily for 16-48 weeks. Therapy was well tolerated; fatigue and hyperlipidemia were the most frequent dose-limiting toxicity and necessitated dose reductions in 14 patients. Two patients achieved a complete response, and 3 responded partially for a total response rate of 20% (95% confidence interval: 4-36%). Responses occurred primarily in patients with limited tumor burden and disease confined to the skin and lymph nodes. Significant elevations in peripheral blood 2'-5'-oligoadenylate synthetase activity and natural killer activity were observed with therapy. The magnitude of these changes, however, was not predictive of response. Biopsy specimens of two responding lesions showed extensive necrosis of tumor. One specimen showed large aggregates of melanophages in association with tumor. The combination of isotretinoin and IFN-alpha is an active, easily administered regimen with acceptable toxicity for metastatic malignant melanoma.
Triozzi
P L
PL
Arthur G. James Cancer Hospital and Research Institute, The Ohio State Comprehensive Cancer Center, Columbus, Ohio, USA.
Walker
M J
MJ
Pellegrini
A E
AE
Dayton
M A
MA
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D015474:Isotretinoin / Q000009:adverse effects / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009336:Necrosis; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000473:pathology / Q000628:therapy*
D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D015088:2',5'-Oligoadenylate Synthetase; D015474:Isotretinoin