16 THERAPY

Interferon-a -a tmIy broad spectrum drug?

The use of interferon-a (INFa) in treating both cancer and viral disease is increasing. It may be anticipated that new indications will be discovered for this agent, making it one of the truly broad-spectrum drugs currently available.

Recombinant IFNa-2b is currently approved or officially indicated as an antiproliferative agent in hairy cell leukaemia and AIDS-related Kaposi's sarcoma. It is also approved for use as an antiviral agent for Condyloma acuminata (venereal warts) and most recently for hepatitis C (non-A, non-B hepatitis). IFNa is not curative in these diseases, but does produce prolonged disease remissions without causing life-threatening toxicities.

Fortunately, patients gradually become tolerant to the 'flu-like' syndrome seen with IFNa.

Therapy is best given via long-term outpatient self-injection. A long biological half-life of 3 to 4 days in terms of antiviral effects facilitates a convenient dosing schedule of 3 injections per week.

The number of official indications for IFNa is set to increase to include more haematol02ical malignancies as well as other viral diseases. However, the compound has already gained a unique niche in 2 different therapeutic categories, and is the ftrst recombinant protein to demonstrate such broad-based signiftcant therapeutic efficacy.

Activity in solid tumours and baematoIogiad C8DlB'S

The level of interferon activity remains low in solid tumours such as renal cell carcinoma and malignant melanoma. Nonetheless, objective responses are possible without inducing significant bone marrow damage. A greater degree of activity is consistently observed in haematological cancers. In chronic myelogenous leukaemia, IFNa induces a high response rate, with some patients losing all genetic signs of malignancy. Other responsive haematological malignancies include cutaneous T cell lymphomas and low grade non-Hodgkin's lymphomas. The drug is particularly active in multiple myeloma when used to prolong remissions obtained by cytotoxic drug combinations.

Exciting pilot studies have been done with locoregional IFNa therapy. Good responses have been seen with intraperitoneal therapy of ovarian cancer, topical cervix treatments and intravesicular therapy of superficial bladder carcinoma. Studies show that local IFNa is both well tolerated and effective when directly exposed to tissues in high concentrations. Clearly, other locoregional uses of IFNa will be explored in the future.

The combination of IFNa with other agents has been disappointing. This may be due to the need to

3 Apr 1l1li3 INPHARMAe

lower the dose of cytotoxic drugs when combined with IFNa. A notable exception is the combination of fluorouracil with IFNa in advanced colorectal carcinoma. In this setting, high response rates were described in pilot studies even though fluorouracil toxicity is enhanced.

Dorr K1'. Intaferon-a1pba in malignant and viral diJeues. A review. Drugs 45: 177-211. Feb 1993 .."moo

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