YOU ARE NOW CONNECTED TO THE TOXLINE (1981 FORWARD, NON-ROYALTY) FILE. ==INTERFERON, ALPHA FOR MELANOMA== 1 AUTHOR Ernstoff MS TITLE DMS 9217-A Phase II Protocol of Interferon and Hydralazine in Patients with Metastatic Renal Cell Carcinoma or Metastatic Melanoma SOURCE FEDRIP DATABASE, NATIONAL TECHNICAL INFORMATION SERVICE (NTIS) ABSTRACT RPROJ/FEDRIP MELANOMA; KIDNEY; INTERFERONS; HYDRALAZINE; CLINICAL TRIALS, PHASE II; CARCINOMA, RENAL CELL OBJECTIVES: The goals of this study are to determine the anti-cancer activity of the combination of interferon-alpha and hydralazine and to determine the safety and side-effects of this combined treatment. One way that hydralazine acts on the blood supply to the tumor is by producing a substance called nitric oxide. Another goal of the study is to test the levels of nitric oxide in the blood at different time points. PLAN/METHODOLOGY: Patients will be treated with interferon alpha by subcutaneous injection 3 times, weekly for 8 weeks. Hydralazine will be started one day prior to the interferon alpha at a dose of 25 mg by mouth four times a day. This dose will be escalated after 4 days to 50 mg qid and then to 100 mg qid 4 days later. Disease evaluation will occur after 8 weeks. Patients with progressive disease will go off study. All other patients will continue treatment. Patients will have peripheral blood (50cc) drawn prior to treatment, weekly during the first 4 weeks and at the end of the first 8 week cycle (a total of 300cc over the first 8 weeks). During subsequent cycles, blood will be drawn every other week (200cc/8 weeks). Initially 18 people are expected to participate in this study at Dartmouth-Hitchcock Medical Center, although it is possible that up to 34 people will participate depending on the initial rate of response to the treatment. RESULTS/PROGRESS TO DATE: Number of participants in past year enrolled at Dartmouth: 3 female; 0 male. Total number of participants since starting study at Dartmouth: 12 female; 15 male. From this study, it has recently been discussed that patients should take medications after meals. Patients tolerating dosages well nonetheless. Nothing else new has arisen as a new discovery. Patients have complained of nausea (grade 2) if they take medications late at night. 5 AUTHOR Ludwig CU TITLE [Possibilities and limits of the use of interferons in the clinic] SOURCE Schweiz Med Wochenschr; VOL 119, ISS 44, 1989, P1539-43 (REF: 41) ABSTRACT Only the recent production of large amounts of highly purified recombinant interferons has made it possible to elucidate precisely the in vitro and in vivo effect of alpha- and gamma-interferon. Interferon-alpha has significantly widened the treatment modalities for some rare tumors such as hairy cell leukemia and chronic myelogenous leukemia. Although treatment results in solid tumors are disappointing, tumor regression greater than 50% is achieved in 15-25% of patients with hypernephroma or melanoma, cancers highly resistant to cytotoxic drugs. The solid tumors must be treated with high doses of interferon-alpha which causes severe side effects. Interferon-induced toxicity can be reduced by continuous subcutaneous infusion. Interferon-alpha is also used for the treatment of viral diseases such as chronic hepatitis-B, as well as for patients with AIDS and Kaposi sarcoma. Other virus infections such as herpes simplex and condylomata acuminata represent the few established indications for treatment with interferon-beta. Interferon-gamma has distinct immunomodulatory effects in vitro and in vivo, although the clinical significance of this potential has not yet been established. Thus far the treatment results in tumor patients have been poor. The future will show if the combination of interferons with other biological response modifiers, such as tumor necrosis factor or interleukin-2, or with cytotoxic drugs, brings further progress in cancer treatment. 7 AUTHOR Budd GT AUTHOR Boycott JM AUTHOR Medendorp SV AUTHOR Novak C AUTHOR Tubbs R AUTHOR et al TITLE Phase I clinical trial of interleukin 2 and alpha-interferon: toxicity and immunologic effects SOURCE Cancer Res.; VOL 49 ISS Nov 15 1989, P6432-6436, (REF 27) ABSTRACT IPA COPYRIGHT: ASHP Fifty-five patients with advanced malignancies were treated with a combination of interleukin 2 0.1-2.0x106 units/sq m by intravenous bolus and alpha-interferon (I) 0.1-10x106 units/sq m intramuscularly on Mondays, Wednesdays and Fridays. Myelosuppression was dose limiting and related primarily to I dosage. Neutropenia was observed in 3 of 6 patients at the highest combined dosage level. Mild hypotension, fever, chills and malaise were also observed. Three partial responses and one minor response were observed in patients with malignant melanoma, renal cell carcinoma and breast cancer. 9 AUTHOR Kirkwood JM AUTHOR Ernstoff MS AUTHOR Davis CA AUTHOR Reiss M AUTHOR Rudnick SA AUTHOR et al TITLE Comparison of intramuscular and intravenous recombinant alpha-2 interferon in melanoma and other cancers SOURCE Ann. Intern. Med.; VOL 103 ISS Jul 1985, P32-36, (REF 12) ABSTRACT IPA COPYRIGHT: ASHP Intramuscular and intravenous routes of administration of recombinant alpha2-interferon (SCH-C81-082-01; SCH-C82-050-01; I) at dosages of 3, 10, 30, 50, or 100 MU/d for up to 4 wk, were compared in 33 patients with melanoma and other cancers. Dose limiting toxicities, including neutropenia, elevated hepatocellular enzyme levels, fatigue, and disturbed mentation, correlated with differing serum pharmacokinetics of I. Dose limiting toxicity occurred at all dosages \GT/ 10 MU/d, 6-9 days treatment, in the IM study but only at 100 MU/d, at a median of day 8, in the IV injected group. Twenty-three patients had metastatic melanoma and 4 had objective partial or complete responses at dosages of 10-50 MU/d in the first month. Two patients with complete responses are free of tumor after 2.5 yr follow up. A fifth patient had delayed complete regression and remained free of disease at 26 months. Interferon had antitumor activity against melanoma by both routes tested, at dosages of 10-50 MU/d.