Tumor-Suppressor Genes and Oncogenes

The combination of Dacarbazine (DTIC) with alphainterferon has consistently shown a 30% remission rate in patients with disseminated malignant melanoma (Thomson et al., 1987; Guillou et al., 1989; Mulder et al., 1990). Although some of these remissions, in particular the complete remissions are prolonged, overall results are not satisfactory. Recently, a synergistic effect has been described between 5-fluorouracil (5-FU) and alpha-interferon in vitro (Elias & Cussman, 1988), particularly in colon carcinoma in vivo (Wadler et al., 1989), but also in a patient with melanoma metastatic to the cerebrum (Jacobs et al., 1989). We have tested the combination of alpha-interferon (Roferon), 5-FU and DTIC in 26 patients with disseminated malignant melanoma. Eligible for treatment were patients with histologically proven disseminated malignant melanoma, who had not received previous sytemic therapy before, had progressive disease, and gave informed consent. Excluded were patients with evidence of central nervous system metastasis on presentation, or uncontrolled other diseases. Work-up consisted of chest X-ray, liver echography or CT scanning, blood chemistry and physical examination before every course and monthly in case of remission. Chemotherapy consisted of intravenous DTIC, 750 mg m2 day 1 and every 4 weeks, intravenous 5-FU 1,000 mg m-2 on day 14 and every 4 weeks. Roferon was given daily in a dose of 9 million units subcutaneously, the first 3 days 3 million units were given. One course was 4 weeks of treatment, tumour response was evaluated after every two courses, treatment was stopped in case of progression, otherwise six