Adjuvant therapy with recombinant interferon alfa-2a in metastasized malignant melanoma

Recombinant alpha-2a interferon (IFN alpha-2a; Roferon-A) was administered as adjuvant therapy in 21 patients with malignant melanoma stage IIa or IIb after surgical removal of all detectable metastases. Patients received 9 x 10(6) units of IFN alpha-2a s.c. 3 times weekly over 6 months. One patient was treated over 12 months. Relapses occurred in 5 of the 21 patients during therapy, and 10 patients developed new metastases a few weeks or months after the end of therapy. Of the 15 patients with recurrent disease, 9 have since died. One patient without any relapse died of a myocardial infarction 5 months after the start of therapy. Comparison of the 21 treated patients with an untreated historical matched control group did not show any prolongation of the recurrence-free period in the interferon-treated group.     

Recombinant interferon alfa-2b in plaque-phase mycosis fungoides. Intralesional and low-dose intramuscular therapy

A two-part clinical trial was conducted to determine the therapeutic efficacy of recombinant interferon alfa-2b in plaque-phase mycosis fungoides. In an initial randomized double-blind study, each of six patients had two representative plaques injected intralesionally with 1 X 10(6) U of recombinant interferon alfa-2b per site and two control plaques injected with placebo three times weekly for four consecutive weeks. Complete clinical regression of disease was observed at ten of 12 recombinant interferon alfa-2b sites compared with one of 12 placebo-treated sites four weeks after treatment with injections was stopped. Subsequently, in an open-labeled study, five of these patients were treated intramuscularly with 5 X 10(6) U of recombinant interferon alfa-2b three times weekly for four weeks and two patients were treated with a second, more extended course of therapy lasting 12 to 16 weeks. Three of the five patients treated systemically showed some improvement overall, but the responses were judged not to be clinically significant. The differential response observed from intralesional and intramuscular injections may be related to differences in concentration of recombinant interferon alfa-2b achieved in lesional skin by the two methods of administration.     

Treatment of cutaneous squamous cell carcinomas by intralesional interferon alfa-2b therapy.

BACKGROUND AND DESIGN--Intralesional recombinant interferon alfa-2b has been shown to be effective in the treatment of actinic keratoses and basal cell carcinomas. This open-label study was designed to evaluate the effectiveness and cosmetic result of this therapy on actinically induced, primary cutaneous squamous cell carcinomas. Thirty-six squamous cell carcinomas (28 invasive lesions and 8 in situ lesions) ranging in size from 0.5 to 2.0 cm in the longest dimension were treated with interferon alfa-2b 1.5 million units injected intralesionally three times per week for 3 weeks. Eighteen weeks following therapy, the treatment sites were excised and examined for histologic evidence of remaining tumor. RESULTS--Thirty-three (97.1%) of 34 evaluable lesions revealed an absence of squamous cell carcinoma histologically after therapy, although three biopsy specimens (8.8%) obtained after treatment showed actinic keratoses, for an overall complete response rate of 88.2%. The lesion not eliminated after treatment was an invasive squamous cell carcinoma. The investigators and patients independently judged 93.9% of cases to have a very good or excellent cosmetic result. Adverse reactions were limited to those influenzalike symptoms well recognized to occur with interferon therapy and these were well tolerated. Only one patient discontinued therapy due to side effects. CONCLUSIONS--This trial demonstrates that intralesional interferon is effective in the treatment of small sun-induced squamous cell carcinomas with well-tolerated side effects and a highly acceptable cosmetic result.     

Adjuvant therapy of melanoma patients with gamma interferon

In a pilot study, 25 patients with high-risk malignant melanomas (a tumor thickness of more than 3 mm and/or a prognostic index of more than 13) and 15 patients with regional lymph-node metastases from malignant melanoma underwent standard surgical procedures. Afterwards, they were treated with gamma interferon in an adjuvant setting. Gamma interferon (200 micrograms) was given subcutaneously three times a week for 6 months. For three times a week for 6 months. For 25 patients, the follow-up has been 12 months or more; for 15 patients, it has been between 7 and 12 months. Tumor relapse occurred in 9 of 25 patients (36%) with high-risk primary tumors and in 5 of 15 patients (33%) with lymph-node metastases. Since these tumor-progression rates are in the same range as those in comparable patients, who did not undergo adjuvant therapy, one can conclude that the adjuvant gamma interferon regimen used is not effective in patients with high-risk malignant melanomas.     

Developing indications for the use of sentinel lymph node biopsy and adjuvant high-dose interferon alfa-2b in melanoma

OBJECTIVES: To convene a multidisciplinary panel of dermatologists, surgical oncologists, and medical oncologists to formally review available data on the sentinel lymph node (SLN) biopsy procedure and high-dose adjuvant interferon alfa-2b therapy for patients with melanoma and to rate the "appropriateness," "inappropriateness," or "uncertainty" of the procedure and therapy to guide clinical decision making in practice. PARTICIPANTS: The panel comprised 13 specialists (4 dermatologists, 4 oncologists, and 5 surgeons) from geographically diverse areas who practiced in community-based settings (n = 8) and academic institutions (n = 5). Participants were chosen based on recommendations from the relevant specialty organizations. EVIDENCE: A formal literature review was conducted by investigators at Protocare Sciences Inc, Santa Monica, Calif, on the risks and benefits of performing an SLN biopsy in patients with stage I or II melanoma and adjuvant interferon alfa-2b therapy in patients with stage II or III disease. The MEDLINE database was searched from 1966 through July 2000, and supplemental information was obtained from various cancer societies and cancer research groups. Panel participants were queried on additional sources of relevant information. Unpublished, presented data were included in abstract form on 1 recently closed clinical trial. CONSENSUS PROCESS: The RAND/UCLA Appropriateness Method was used to review and rate multiple clinical scenarios for the use of SLN biopsy and interferon alfa-2b therapy. The consensus method did not force agreement. CONCLUSIONS: The panel rated 104 clinical scenarios and concluded that the SLN biopsy procedure was appropriate for primary melanomas deeper than 1.0 mm and for tumors 1 mm or less when histologic ulceration was present and/or classified as Clark level 4 or higher. The SLN biopsy was deemed inappropriate for nonulcerated Clark level 2 or 3 melanomas 0.75 mm or less in depth and uncertain in tumors 0.76 to 1.0 mm deep unless they were ulcerated or Clark level 4 or higher. Interferon alfa-2b therapy was deemed appropriate for patients with regional nodal and/or in-transit metastasis and for node-negative patients with primary melanomas deeper than 4 mm. The panel considered the use of interferon alfa-2b therapy uncertain in patients with ulcerated intermediate primary tumors (2.01-4.0 mm in depth) and inappropriate for node-negative patients with nonulcerated tumors less than 4.0 mm deep. Specialty-specific ratings were conducted as well.     

Postoperative adjuvant therapy with interferon alfa-2B following laser surgery of condylomata acuminata

Sexually transmitted diseases caused by human papilloma viruses, such as condylomata acuminata, are increasing in incidence and are often difficult to treat because of their tendency to recur. Many reports in the literature document the usefulness of interferons topically or systemically in these diseases. A randomized study was conducted to evaluate interferon Alfa-2b (Intron A) as adjuvant therapy following CO2 laser surgery of condylomata acuminata. A low-dose regimen was administered (two courses with 1 million I.U. s.c. daily for 6 days with a 2-week interval between the courses) and had hardly any side-effects. The recurrence rate in the therapy group was significantly reduced (42% vs 81%), so routine prophylaxis of recurrence with interferons in condylomata acuminata should be discussed.