Synthetic Anthracycline Produces High Response Rates in SCLC

TOKYO, Japan—Amrubicin (SM-5887), a completely synthetic anthra-cycline, is "highly active" and well tolerated in small-cell lung cancer (SCLC), Shunichi Negoro, MD, of the Department of Pulmonary Medicine, Osaka City General Hospital, Japan, said at the 9th World Conference on Lung Cancer.

Presenting data on behalf of the West Japan Thoracic Oncology Group, Dr. Negoro said that amrubicin produced a response rate of 79% as a single agent in previously untreated, extensive-disease SCLC.

"This extraordinarily high response rate is remarkable and far exceeds the response rate of recent promising new agents, including topoisomerase-I inhibitors and taxanes," Dr. Negoro said. Amrubicin was previously shown to have a more potent antitumor effect and fewer toxicities than doxorubicin.

Median survival time was 11.7 months, which Dr. Negoro said "favorably compares" to the 10- to 11-month survival time commonly reported for standard chemotherapy regimens, including cisplatin (Platinol)/etoposide (VePesid).

The major toxicity of the trial was myelosuppression, including grade 4 leukopenia in 12% of patients and neutropenia in 42%. Grade 3–4 thrombocytopenia and anemia both occurred in 21% of patients. The only nonhematologic toxicities greater than grade 3 were anorexia and alopecia. This toxicity profile is "well acceptable" for the treatment, he said.

Furthermore, while acute toxicities of doxorubicin and amrubicin are comparable qualitatively, with amrubicin, cardiotoxicity or other delayed-type toxicities such as those observed with doxorubicin are rare.

According to Dr. Negoro, amrubicin is converted to an active form that is up to 200 times more cytotoxic; both forms inhibit topoisomer-ase II. In experimental studies, multiple intravenous injections of amrubicin were found to be more effective than a single injection. This is likely because multiple injection allows more of amrubicin’s active form to accumulate in the tissue of the tumor.

Phase II Trial

The phase II trial described by Dr. Negoro included 35 patients under 80 years of age with histologically or cytologically confirmed, previously untreated, extensive-disease SCLC. All had performance status of 0–2, a life expectancy of 2 months or more, and adequate organ function.

The treatment schedule consisted of intravenously injected amrubicin 45 mg/m²/d for 3 days with cycles repeated every 21 days.

According to study protocol, treatment was switched to salvage chemotherapy with the standard etoposide/cisplatin regimen—etoposide/carboplatin (Par-aplatin) in some cases—if tumor regression of less than 25% was seen following the first course. Likewise, patients with tumor regression of less than 50% after the second course were switched to salvage chemotherapy.

For 33 evaluable patients, the median age was 66 and the median number of courses of therapy was 4.

The 79% response rate included 5 complete responses (15%) and 21 partial responses (64%). Only five patients were switched to salvage etoposide therapy. For one of those patients, a survival of more than 836 days post-amrubicin therapy has been recorded. "Further trials in combination with other agents are warranted," Dr. Negoro said.