Phase I study of recombinant methionyl human consensus interferon (r-metHuIFN-Con1).
Consensus interferon (r-metHuIFN-Con1) is the product of a gene constructed to code for the most frequent amino acid residues known to occur in subspecies of alpha interferons. Twenty-one patients with advanced malignancy entered this phase I trial with dosing levels of 3, 7.5, 15, 30, and 45 mcg/m2/day given intramuscularly on days 1-5 and 8-10 of each 28-day cycle. The initial dose was randomly given by intravenous, intramuscular, or subcutaneous injection to facilitate pharmacokinetic studies. Vomiting and diarrhea were dose-limiting at 45 mcg/m2/day, preventing completion of therapy. Malaise, flu-like symptoms, nausea, and headache were frequent but tolerable at a dose of 30 mcg/m2/day. Patients were able to escalate to 45 mg/m2/day, suggesting tachyphlaxis to these toxicities. The initial distribution phase (T1/2 alpha) was 4.9-9.0 minutes with a T1/2 beta of 34-415 minutes in three patients for whom sequential values could be determined. r-MetHuIFN-Con1 was absorbed after both subcutaneous and intramuscular administration. 2'5'-Synthetase levels increased following treatment, although no consistent pattern was noted. One partial response was seen in a patient with gastrointestinal carcinoma. The recommended phase II starting dose of r-metHuIFN-Con1 is 30 mg/m2/day using this schedule by any of these routes of administration.
Neidhart
J A
JA
Division of Medicine, University of Texas, M.D. Anderson Hospital and Tumor Institute, Houston.
Schmidt
S
S
Rosenblum
M
M
Raber
M N
MN
Quesada
J R
JR
Alton
N K
NK
Downing
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use*; D016898:Interferon-alpha; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D010976:Platelet Count; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use
D007370:Interferon Type I; D016898:Interferon-alpha; D011994:Recombinant Proteins; C056556:methionyl human consensus alpha interferon