Both in vitro and in vivo studies have demonstrated antiproliferative effects of
interferon alfa-2b (Intron A; Schering-Plough) when tested with human
tumor cells. A clonogenic assay has been widely used to determine its direct antiproliferative effects on human
tumor cells in vitro using colony reduction as a reproducible endpoint. As a single agent,
interferon alfa-2b shows maximum
tumor cell colony reduction when used in high concentrations with continuous cell exposure. Short-term exposure to
interferon alfa-2b does not produce significant
tumor cell colony reduction. Clonogenic assays have also been used to test combinations of
interferon alfa-2b with cytotoxic drugs. Variations in
drug scheduling, sequencing and concentrations have indicated the best combinations which maximize
tumor cell colony reduction. Combinations of
interferon alfa-2b with
doxorubicin,
cisplatin,
vinblastine,
melphalan and
cyclophosphamide have been shown to have at least additive and occasionally synergistic antiproliferative effects. In clinical trials, optimal pairs of agents have been identified frequently combining either
doxorubicin,
cisplatin or
vinblastine with
interferon alfa-2b. Pretreatment with
interferon alfa-2b has been adopted from in vitro studies and applied to most clinical trials. One study has enrolled 135 patients having a variety of advanced or recurrent solid
tumor types, using a schema which combines
interferon alfa-2b and
doxorubicin administration, both given on a weekly basis for three weeks, followed by treatments every two weeks in responding patients. Clinical responses have been seen using this regimen in patients with ovarian, cervical, colorectal and
pancreatic carcinomas and in one
lymphoma patient. Another study has been designed combining
melphalan,
prednisone and
interferon alfa-2b for the treatment of patients with relapsing
multiple myeloma. This is also based upon preclinical data. New methods of administration are being studied giving
interferon alfa-2b as a single agent or in combination with
cisplatin by the intraperitoneal route to patients with relapsing ovarian
carcinomas limited to the peritoneal cavity. This method can maximize both the levels of
interferon alfa-2b as well as the
tumor cell exposure time.