A phase II study of ABT-751 in patients with advanced non-small cell lung cancer.
OBJECTIVE
To determine the tolerability and efficacy of ABT-751, an oral antimitotic agent that inhibits polymerization of microtubules, in patients with advanced taxane-refractory non-small cell lung carcinoma (NSCLC).


METHODS
Eligibility was limited to patients with recurrent or metastatic NSCLC who had received one to two cytotoxic chemotherapy regimens, had a performance status of zero to one, and adequate organ function. Treatment included ABT-751 200 mg daily for 21 consecutive days, followed by 7 days off drug. Objectives were to determine response rate, time to tumor progression, survival, and tolerability of ABT-751.


RESULTS
All 35 enrolled patients were assessable for survival, response, and tolerability. Median time to tumor progression and overall survival were 2.1 and 8.4 months, respectively. The objective response rate was 2.9%. One patient achieved a partial response that was ongoing 567 days after initial documentation. Treatment was well tolerated; fatigue, constipation, and dehydration were the only treatment related, grade three adverse events occurring in more than one patient. Incidence of grade 3/4 hematologic and blood chemistry toxicities was acceptable, and ABT-751 was not associated with myelosuppression.


CONCLUSIONS
ABT-751 associated toxicity was acceptable. The median time to progression and overall survival as demonstrated for ABT-751 were comparable to other agents considered active in this patient population and to current treatments approved for second-line NSCLC. The novel antimitotic targeting of ABT-751 in combination with the compound's acceptable nonmyelosuppressive toxicity profile and efficacy similar to agents currently in use in this setting, warrant further evaluation of this compound in combination with other cytotoxic agents in advanced NSCLC.
Mauer
Ann M
AM
University of Chicago Medical Center, Chicago, Illinois 60637, USA. ann.mauer-md@advocatehealth.com
Cohen
Ezra E W
EE
Ma
Patrick C
PC
Kozloff
Mark F
MF
Schwartzberg
Lee
L
Coates
Andrew I
AI
Qian
Jiang
J
Hagey
Anne E
AE
Gordon
Gary B
GB
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*; D011795:Surveys and Questionnaires; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
C490492:ABT751; D013449:Sulfonamides