Phase I study of gemcitabine, docetaxel and imatinib in refractory and relapsed solid tumors.
OBJECTIVE
In a phase I study, the combination of gemcitabine and imatinib was well tolerated with broad anticancer activity. This phase I trial evaluated the triplet of docetaxel, gemcitabine and imatinib.


METHODS
Imatinib was administered at 400 mg daily on days 1-5, 8-12 and 15-19. Gemcitabine was started at 600 mg/m(2) at a rate of 10 mg/min on days 3 and 10 and docetaxel at 30 mg/m(2) on day 10, on a 21-day cycle. Diffusion and dynamic contrast-enhanced perfusion MRI was performed in selected patients.


RESULTS
Twenty patients with relapsed/refractory solid tumors were enrolled in this IRB-approved study. The mean age was 64, and mean ECOG PS was 1. Two patients were evaluated by diffusion/perfusion MRI. After two grade 3 hematological toxicities at dose level 1, the protocol was amended to reduce the dose of imatinib. MTDs were 600 mg/ m(2) on days 3 and 10 for gemcitabine, 30 mg/ m(2) on day 10 for docetaxel, and 400 mg daily on days 1-5 and 8-12 for imatinib. Dose limiting toxicities after one cycle were neutropenic fever, and pleural and pericardial effusions. The best response achieved was stable disease, for six cycles, in one patient each with mesothelioma and non small cell lung cancer (NSCLC) at the MTD. Two patients with NSCLC had stable disease for four cycles.


CONCLUSIONS
An unexpectedly low MTD for this triplet was identified. Our results suggest drug-drug interactions that amplify toxicities with little evidence of improved tumor control.
Saraiya
Biren
B
The Cancer Institute of New Jersey, UMDNJ-Robert Wood Johnson Medical School, 195 Little Albany St., New Brunswick, NJ 08901, USA. saraiybi@umdnj.edu
Chugh
Rashmi
R
Karantza
Vassiliki
V
Mehnert
Janice
J
Moss
Rebecca A
RA
Savkina
Nelli
N
Stein
Mark N
MN
Baker
Laurence H
LH
Chenevert
Thomas
T
Poplin
Elizabeth A
EA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D038524:Diffusion Magnetic Resonance Imaging; D000077143:Docetaxel; D004334:Drug Administration Schedule; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D020714:Maximum Tolerated Dose; D008824:Michigan; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009515:New Jersey; D055420:Perfusion Imaging; D010879:Piperazines / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage; D043823:Taxoids / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D000093542:Gemcitabine
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000068877:Imatinib Mesylate; D000093542:Gemcitabine