A phase I/II study of GTI-2040 plus docetaxel as second-line treatment in advanced non-small cell lung cancer: a study of the PMH phase II consortium.
BACKGROUND
GTI-2040, an antisense oligonucleotide, targets the ribonucleotide reductase R2 subunit, critical for DNA synthesis. This study determined the recommended phase II dose (RP2D) of docetaxel plus GTI-2040, toxicity, and response rate in advanced non-small cell lung cancer (NSCLC).


METHODS
Advanced solid tumor patients, preferably with platinum-treated NSCLC, performance status 0 to 2, no symptomatic central nervous system metastases, adequate organ and bone marrow function, and >or=1 prior chemotherapy regimen were treated with escalating doses of GTI-2040 given by 14-day continuous intravenous infusion (CVI) plus docetaxel every 21 days.


RESULTS
Twenty-nine patients were treated, (24 NSCLC, 3 hormone-refractory prostate cancer, 1 head and neck, and 1 small cell lung cancer). GTI-2040 5 mg/kg as CVI for 14 days plus docetaxel 75 mg/m(2) intravenously every 21days was determined as the RP2D. Dose-limiting toxicity was not seen. Two patients at RP2D developed grade 4/5 febrile neutropenia. One prostate specific antigen response was seen in phase I, but no objective tumor responses in the NSCLC patients. Median time to progression was 3.4 months, 3.2 months in the NSCLC patients treated at RP2D.


CONCLUSIONS
Activity of the combination at RP2D, GTI-2040 5 mg/kg/d x 14 days by CVI plus docetaxel 75 mg/m(2) does not seem superior to docetaxel alone in previously treated NSCLC.
Leighl
Natasha B
NB
Princess Margaret Hospital Phase 2 Consortium, Ontario, Canada. Natasha.Leighl@uhn.on.ca
Laurie
Scott A
SA
Chen
Xueyu E
XE
Ellis
Peter
P
Shepherd
Frances A
FA
Knox
Jennifer J
JJ
Goss
Glenwood
G
Burkes
Ronald L
RL
Pond
Gregory R
GR
Dick
Christopher
C
Yen
Yun
Y
Zwiebel
James A
JA
Moore
Malcolm J
MJ
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
D009838:Oligodeoxyribonucleotides; D043823:Taxoids; D000077143:Docetaxel; C464617:GTI2040
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