Increased effectiveness of interferon alfa-2b following active specific immunotherapy for melanoma.

Abstract

PURPOSE:

To determine whether interferon alfa-2b (IFN-alfa; intron-A, Schering Corp, Kenilworth, NJ) can induce a remission in patients previously treated with active specific immunotherapy (therapeutic melanoma vaccine) without response.

PATIENTS AND METHODS:

Eighteen patients with disseminated melanoma who had failed to respond to at least five injections of Melacine therapeutic melanoma vaccine (Ribi ImmunoChem Research, Inc, Hamilton, MT) were then treated IFN-alfa after a 4-week interval. IFN-alfa 5 or 6 x 10(6) U/m2 was self-administered three times a week subcutaneously by melanoma patients for at least 2 months. Computed tomographic (CT) scans of the chest, abdomen, and pelvis and magnetic resonance imaging of the brain were performed within 4 weeks before treatment as a baseline, and then at 2-month intervals during treatment to evaluate response. All 18 patients were HLA-typed before treatment. The frequency of cytolytic T-cell precursors (pCTL) in the blood had been measured weekly in 13 of the patients during treatment with Melacine.

RESULTS:

Eight of 18 patients (44.4%) had a major objective clinical response induced by IFN-alfa, including site-specific complete remissions in five. Responses lasted a median of 11 months. The median survival duration of the responders has not been reached, and exceeds 32 months. The group as a whole had a median survival duration of 10.1 months, and nonresponders lived 7.3 months. Cytolytic T-cell precursors had been increased by immunization in all five responding patients tested, but also in five of eight nonresponders. There was no association of response to IFN-alfa with specific HLA phenotypes, in contrast to our previous results with melanoma theraccine alone.

CONCLUSION:

These data suggest an additive effect of active specific immunotherapy and IFN-alfa on the objective response rate, perhaps through upregulation of HLA molecules and tumor-associated antigens on the tumor cell by IFN-alfa, after immunization of the patient by Melacine. This treatment may have improved survival over that expected in metastatic melanoma.

• Authors: M S Mitchell, J Jakowatz, W Harel, G Dean, L Stevenson, W D Boswell, S Groshen
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 12 Issue 2 Pg. 402-11 (Feb 1994) ISSN: 0732-183X [Print] United States
• PMID: 8113848 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cancer Vaccines
• Interferon alpha-2
• Interferon-alpha
• Melacine
• Recombinant Proteins

Topics

• Adult
• Aged
• Cancer Vaccines (therapeutic use)
• Female
• Humans
• Immunotherapy, Active (methods)
• Interferon alpha-2
• Interferon-alpha (therapeutic use)
• Male
• Melanoma (diagnostic imaging, secondary, therapy)
• Middle Aged
• Recombinant Proteins
• Remission Induction
• Tomography, X-Ray Computed
• Treatment Outcome