TOKYO, JapanAmrubicin (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
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
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 regimenetoposide/carboplatin
(Par-aplatin) in some casesif 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.