Phase 2 study of cryptophycin 52 (LY355703) in patients previously treated with platinum based chemotherapy for advanced non-small cell lung cancer.
BACKGROUND
Cryptophycin 52 is a novel antitubulin drug with in vitro and in vivo activity in non-small cell lung cancer. Based upon promising Phase 1 data, a multicenter trial was performed to evaluate the drug in previously treated non-small cell lung cancer (NSCLC).


METHODS
Patients with Stage IIIb (pleural effusion) or Stage IV NSCLC and performance status 0-1 with adequate organ function who had received at least one and no more than two prior chemotherapy regimens (one of which must have contained a platinum agent) were eligible. Cryptophycin 52 was administered at a dose of 1.5 mg/m(2) day 1 and 8 every 3 weeks. Patients were reassessed every two cycles.


RESULTS
Twenty-six patients were enrolled of whom 25 are evaluable for toxicity and response. There were no responders, toxicity was predominantly neurologic in the form of peripheral neuropathy and constipation. After the first 12 patients were enrolled, the dose was lowered to 1.125 mg/m(2) day 1 and 8. Toxicity was substantially reduced with this maneuver. Median survival was 4.1 months. The median number of cycles was two, however ten patients received four or more courses of therapy.


CONCLUSIONS
Cryptophycin 52 failed to produce measurable responses utilizing this schedule. In 40% of patients there was evidence of disease stabilization. Toxicity at 1.5 mg/m(2) was unacceptable. Since activity and toxicity may be dose and schedule dependent, other schedules of cryptophycin 52 should be considered.
Edelman
Martin J
MJ
Division of Hematology/Oncology, University of Maryland Greenebaum Cancer Center, Baltimore, MD 21201-1595, USA.
Gandara
David R
DR
Hausner
Petr
P
Israel
Valerie
V
Thornton
Donald
D
DeSanto
Jennifer
J
Doyle
L Austin
LA
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D047630:Depsipeptides; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007769:Lactams / Q000627:therapeutic use*; D007783:Lactones / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D016879:Salvage Therapy; D015996:Survival Rate; D017211:Treatment Failure
D000970:Antineoplastic Agents; D047630:Depsipeptides; D007769:Lactams; D007783:Lactones; D009944:Organoplatinum Compounds; C114033:cryptophycin 52