A PHASE-I STUDY OF RECOMBINANT HUMAN INTERFERON-ALPHA-2B COMBINED WITH 5-FLUOROURACIL AND CISPLATIN IN PATIENTS WITH ADVANCED CANCER

To determine the maximum tolerated dose (MTD) of escalating doses of i nterferon-alpha-2b (IFN, Intron A) with 5-fluorouracil (5-FU) and cisp latin (DDP) in patients with advanced cancer, 15 patients were accrued between May 1990 and July 1991. Primary sites were unknown (3), color ectal (3), head and neck (2), lung (2), gynecologic (1), gallbladder ( 1), sarcoma (1), anal canal (1) and pancreas (1). IFN was given s.c, o n days 1-5 and then three times weekly with DDP (75 mg/m(2), day 1) an d 5-FU [750 mg/m(2), days 1-5, continuous infusion (CI) on a 28-day cy cle. The first two patients treated at level I(3 x 10(6) U/m(2) s.c.) experienced possible neurotoxic deaths [massive cerebrovascular accide nt (CVA) and metabolic encephalopathy], and patient 3 had a grade 4 to xicity of performance status decline. Analysis of these events led us to exclude the enrollment of patients on i.v. morphine and of those wi th prior exposure to DDP. This resulted in grade 3 toxicity in terms o f nausea, vomiting, fatigue and leukopenia but in no further CNS event . All patients were evaluable for toxicity but only ten were evaluable for response. Only two partial responses were seen, one in a patient with an unknown primary tumour and one in a patient with head and neck cancer. The combination of IFN is possible with 5-FU and DDP. The rec ommended dose of IFN is 2x10(6) U/m(2) s.c. in patients with no prior exposure to DDP or i.v. morphine, given together with 5-FU (750 mg/m(2 ), days 1-5, CI) and DDP (75 mg/m(2), day 1) on a 28-day cycle.