Phase II trial of T138067, a novel microtubule inhibitor, in patients with metastatic, refractory colorectal carcinoma.
BACKGROUND
This study was conducted before the approval of oxaliplatin, cetuximab, and bevacizumab and was designed to evaluate a novel microtubule targeting agent, T138067, in patients with metastatic colorectal cancer (CRC) previously treated with irinotecan and 5-fluorouracil.


METHODS
Patients from 3 institutions were enrolled over 4 months and treated with T138067 on days 1, 8, and 15 of a 21-day cycle. Disease evaluation was performed after 9 weeks.


RESULTS
Treatment was tolerable with moderate hematologic and gastrointestinal toxicity. Neurotoxicity, an expected side effect, was minimal. Among 23 evaluable patients, there were no responses. Median time to tumor progression was 1.4 months and median survival was 9.3 months.


CONCLUSIONS
T138067 at this dose and schedule was well tolerated by patients with CRC. However, there was no evidence of clinical activity for T138067 in 5-fluorouracil/irinotecan-refractory CRC. The long median survival likely reflects availability of other agents and/or patient selection.
Berlin
Jordan D
JD
Vanderbilt University Medical Center, Nashville, TN 37232-6307, USA. jordan.berlin@vanderbilt.edu.
Venook
Alan
A
Bergsland
Emily
E
Rothenberg
Mace
M
Lockhart
A Craig
AC
Rosen
Lee
L
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D016879:Salvage Therapy / Q000379:methods; D013449:Sulfonamides / Q000627:therapeutic use*; D005464:Fluorobenzenes; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
D000970:Antineoplastic Agents; D002166:Camptothecin; D005472:Fluorouracil; D000077146:Irinotecan; D013449:Sulfonamides; C119368:batabulin; D005464:Fluorobenzenes; D005466:Fluorocarbons; D000096926:Benzenesulfonamides