Patients who experience severe reactions to Roferon-A will usually recover within days after discontinuation of therapy, given appropriate supportive care. Coma has been observed in 0.4% of cancer patients in clinical trials.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group:
Antineoplastic and immunomodulating agents, Interferons
ATC Code L03AB04
Roferon-A has been shown to possess many of the activities of the so-called natural human alpha-interferon preparations. Roferon-A exerts its antiviral effects by inducing a state of resistance to viral infections in cells and by modulating the effector arm of the immune system to neutralise viruses or eliminate virus infected cells. The essential mechanism for the antitumour action of Roferon-A is not yet known. However, several changes are described in human tumoural cells treated with Roferon-A: HT 29 cells show a significant reduction of DNA, RNA and protein synthesis. Roferon-A has been shown to exert antiproliferative activity against a variety of human tumours in vitro and to inhibit the growth of some human tumour xenografts in nude mice. A limited number of human tumour cell lines grown in vivo in immunocompromised nude mice has been tested for the susceptibility to Roferon-A. In vivo antiproliferative activity of Roferon-A has been studied on tumours including breast mucoid carcinoma, adenocarcinoma of the caecum, colon carcinoma and prostatic carcinoma. The degree of antiproliferative activity is variable.
Unlike other human proteins, many of the effects of interferon alfa-2a are partially or completely suppressed when it is tested in other animal species. However, significant antivaccinia virus activity was induced in rhesus monkeys pre-treated with interferon alfa-2a.
Clinical Trials
Hairy Cell Leukaemia
The therapeutic efficacy of Roferon-A in the treatment of hairy cell leukaemia has been demonstrated in a large trial of 218 patients, of whom 174 were eva luable for efficacy after 16-24 weeks of therapy. Response was observed in 88% of patients (complete response 33%, partial response 55%).
AIDS-related Kaposi's Sarcoma
The efficacy of Roferon-A in the treatment of Kaposi's sarcoma was assessed in 364 patients receiving of 3 to 54 MIU per day. Objective response rates were dose-related, ranging from 14% to 50%, with a daily dose of 36 MIU producing the best overall therapeutic benefit (13.3% complete response, 12.2% partial response). High baseline CD4 lymphocyte count was a favourable prognostic factor for response, with 46% of patients with a CD4 count >400/mm³ responding to Roferon-A. Response to Roferon-A therapy was the strongest prognostic factor for survival.
Chronic Myelogenous Leukaemia (CML)
The efficacy of Roferon-A was assessed in 226 patients with chronic phase CML, and compared with 109 patients receiving chemotherapy (hydroxyurea or busulfan). Both groups had favorable features at diagnosis (less than 10% blasts in the blood) and treatment was initiated with interferon within 6 months of diagnosis. Treatment of patients with CML in the chronic phase leads to the same proportion of patients (85-90%) achieving a haematologic response as treatment with the standard chemotherapy regimens. In addition patients treated with Roferon-A resulted in 8% complete cytogenetic response and 38% partial cytogenetic response versus 9% partial cytogenetic response during chemotherapy. Time to p |
