Small cell lung cancer (SCLC) is generally sensitive to first-line
chemotherapy, but limited disease often recurs and extensive disease is rarely curable. The most common first-line
therapy regimen is
cisplatin (
Platinol; Bristol-Myers Squibb; Princeton, NJ) plus
etoposide (
Etopophos; Bristol-Myers Squibb)--PE, which is associated with overall response rates >80% in patients with limited SCLC. Although it is associated with median survival times of approximately 18-20 months for limited disease, PE yields median survival times of only approximately 8-12 months in patients with extensive disease, and symptom palliation becomes the primary therapeutic goal. The toxicities of PE may undermine quality of life and leave patients more susceptible to adverse events during subsequent
therapies.
Topotecan (
HYCAMTIN; GlaxoSmithKline; Philadelphia, PA), an established treatment for recurrent SCLC, is being investigated in the first-line setting because of its novel mechanism of action; predictable, noncumulative, and manageable toxicities; and potential synergy with other active agents. Several recent phase II trials have generated promising results for
topotecan-based combination regimens, including
topotecan/
paclitaxel (
TAXOL; Bristol-Myers Squibb) (overall response rates 45%-100%),
topotecan/
etoposide (overall response, 95%), and
topotecan,
paclitaxel, and
platinum agent triplets (overall response rates 51%-93%). The most frequent serious toxicity associated with these regimens was reversible and noncumulative
neutropenia, which was generally manageable with supportive care. Additional clinical trials to investigate
topotecan-based combination regimens and confirm their role in the first-line treatment of SCLC are under way.