Intraperitoneal human recombinant interferon alpha-2b in minimal residual ovarian cancer.
Twenty evaluable patients with minimal residual ovarian cancer at second look laparotomy were treated with human recombinant interferon alpha-2b (IFN) intraperitoneally. The dose administered was 50 x 10(6) units once weekly for 8 weeks. Seventeen patients were evaluated by a relaparotomy: five had a pathological complete remission, four a partial response, six patients disease stabilization and two patients had progression. Three patients, two stable and one with clinical progression, had no laparotomy. Nine of the 11 patients with residual tumor smaller than 5 mm had a response, while no response was found in six patients with residuals over 5 mm. The median duration of CR is 11+ months (6-13+ months) after evaluation. For toxicity, 156 treatment cycles could be studied. Fever was seen in 80% of all cycles within 24 h following administration of IFN, in 58 cycles (37%) over 38 degrees C and in 65 cycles (43%) over 39 degrees C. Abdominal pain was slight in 32% and moderate in 3% of all cycles. The peripheral blood leukocyte counts dropped after 52% of all cycles, in 27% below 4.0, in 22% below 3.0, and in one patient below 2.0 x 10(9)/l. IFN dosage was not reduced for leukopenia, but in one patient reduction was necessary for thrombopenia, resulting from insufficient marrow reserve after a previous autologous bone marrow transfusion. Pharmacokinetic studies showed i.p. IFN levels 50-100 times the blood levels. Blood levels were still elevated 2 days after i.p. infusion, but normalized within 1 week on repeated administration. At the second instillation, lower peak serum levels were reached. In conclusion, high doses of i.p. IFN appear to be active in patients with minimal residual disease, with ongoing response in CR patients. Apart from general malaise on the day of treatment, toxicity was acceptable. IFN may be active in patients with minimal residual ovarian cancer through local as well as systemic effects.
Willemse
P H
PH
Department of Medical Oncology, University of Groningen, The Netherlands.
de Vries
E G
EG
Mulder
N H
NH
Aalders
J G
JG
Bouma
J
J
Sleijfer
D T
DT
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D007370:Interferon Type I / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D011994:Recombinant Proteins
D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins