Phase I/II study of gemcitabine and exisulind as second-line therapy in patients with advanced non-small cell lung cancer.
BACKGROUND
The study was designed to evaluate the safety and efficacy of exisulind, a selective apoptotic antineoplastic drug, in combination with gemcitabine as second-line therapy in patients with progressing advanced non-small cell lung cancer.


METHODS
Patients whose disease progressed more than 3 months from completion of first-line chemotherapy were eligible for this phase I/II trial. Primary end points were maximally tolerated dose and time to progression. Patients in the phase I portion of the study were treated with gemcitabine (1250 mg/m) in combination with three escalated dose levels of exisulind. Treatment involved six cycles of gemcitabine and exisulind followed by exisulind maintenance. The study was subsequently expanded to phase II.


RESULTS
Thirty-nine patients (15 in phase I and 24 in phase II) were treated. The regimen was well tolerated with grade 3 fatigue and grade 3 constipation being dose-limiting toxicities. The maximally tolerated dose was not reached. Dose level 3 of exisulind (250 mg twice daily) in combination with gemcitabine was used for phase II. The overall response rates were 7% (phase I), 17% (phase II), and 13% (all). Median time to progression and median and 1-year survival, respectively, were 3.7 and 9.7 months and 33% (phase I); 4.3 and 9.4 months and 41% (phase II); and 4.1 and 9.4 months and 39% (all).


CONCLUSIONS
Although the study met its primary end point of improving time to progression (more than 4.1 months in phase II), we did not observe a clear survival advantage and thus do not plan to further investigate this schedule of gemcitabine and exisulind.
Hoang
Tien
T
Ohio State University College of Medicine and Comprehensive Cancer Center, Columbus, Ohio, USA.
Kim
KyungMann
K
Merchant
Joseph
J
Traynor
Anne M
AM
McGovern
James
J
Oettel
Kurt R
KR
Sanchez
Fredrico A
FA
Ahuja
Harish G
HG
Hensing
Thomas A
TA
Larson
Martha
M
Schiller
Joan H
JH
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D013467:Sulindac / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016019:Survival Analysis; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced; D000093542:Gemcitabine
D003841:Deoxycytidine; D013467:Sulindac; C025463:sulindac sulfone; D000093542:Gemcitabine