Natural interferon alpha(BioPharm Solutions, Inc.)

We experienced a case of advanced renal carcinoma that showed complete remission to interferon-alpha therapy. A 76-year-old male underwent radical nephrectomy for left renal cell carcinoma (pT3b pN0 M0, stage III). Two and a half months later, chest X-ray, computed tomographic (CT) scan and ultrasonography revealed multiple lung metastases and a hepatic metastasis simultaneously. We started the intramuscular administration of natural interferon-alpha (OIF, 5 MIU) combined with cimetidine everyday. It caused leukopenia, a possible side-effect of interferon-alpha. We reduced the dose to three times a week. The lung metastases and hepatic metastases disappeared after 5 and 12 months, respectively. After we reduced the dose to once a week, there was no evidence of disease for 21 months.

In a preliminary non-randomized study, combination therapy with natural (i.e. non-recombinant) interferon-alpha plus cimetidine obtained a high response rate in patients with advanced renal cell carcinoma. We conducted a prospective randomized phase III trial to determine whether combination therapy with natural interferon-alpha plus cimetidine is superior to natural interferon-alpha alone in patients with advanced renal cell carcinoma with pulmonary metastasis.

Patients received 5 million units (MU) natural interferon-alpha per day, five times a week, or the 5 MU natural interferon-alpha regimen plus a daily oral cimetidine. The primary and secondary end points were the response rate, and the time to progression (TTP), respectively.

Between April 1998 and March 2002, 71 patients from 32 institutions were randomly assigned to the 2 treatment groups. One patient in each group did not receive any natural interferon-alpha whatsoever. Two patients in the natural interferon-alpha alone group stopped treatment: on day 9 and on day 10, respectively. In the intent-to-treat analysis, 1 complete response (CR), 4 partial responses (PRs), 16 no changes (NCs), and 12 progressive diseases (PDs) were observed among the 36 patients in the interferon-alpha alone group with a response rate of 13.9%. Of the 35 patients in the natural interferon-alpha plus cimetidine group, there were two CRs, 8 PRs, 13 NCs, and 11 PDs, yielding a response rate of 28.6% (P=0.13). TTP ranged from 9 to 845 days (median 112 days) in the natural interferon-alpha-alone group, and from 31 to 1,568 days (median 125 days) in the natural interferon-alpha plus cimetidine group (P=0.87).

Combined treatment with natural interferon-alpha plus cimetidine for advanced renal cell carcinoma did not result in a significant improvement in response rates or TTP compared to natural interferon-alpha therapy alone.