PMID- 20697775
OWN - NLM
STAT- MEDLINE
DCOM- 20120508
LR  - 20221207
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Print)
IS  - 0167-6997 (Linking)
VI  - 30
IP  - 1
DP  - 2012 Feb
TI  - Phase I study of gemcitabine, docetaxel and imatinib in refractory and relapsed 
      solid tumors.
PG  - 258-65
LID - 10.1007/s10637-010-9504-5 [doi]
AB  - PURPOSE: 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. EXPERIMENTAL DESIGN: 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. DISCUSSION: 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.
FAU - Saraiya, Biren
AU  - Saraiya B
AD  - The Cancer Institute of New Jersey, UMDNJ-Robert Wood Johnson Medical School, 195 
      Little Albany St., New Brunswick, NJ 08901, USA. saraiybi@umdnj.edu
FAU - Chugh, Rashmi
AU  - Chugh R
FAU - Karantza, Vassiliki
AU  - Karantza V
FAU - Mehnert, Janice
AU  - Mehnert J
FAU - Moss, Rebecca A
AU  - Moss RA
FAU - Savkina, Nelli
AU  - Savkina N
FAU - Stein, Mark N
AU  - Stein MN
FAU - Baker, Laurence H
AU  - Baker LH
FAU - Chenevert, Thomas
AU  - Chenevert T
FAU - Poplin, Elizabeth A
AU  - Poplin EA
LA  - eng
GR  - P01 CA085878/CA/NCI NIH HHS/United States
GR  - P30 CA046592/CA/NCI NIH HHS/United States
GR  - P30 CA072720/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
DEP - 20100810
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Benzamides)
RN  - 0 (Piperazines)
RN  - 0 (Pyrimidines)
RN  - 0 (Taxoids)
RN  - 0W860991D6 (Deoxycytidine)
RN  - 15H5577CQD (Docetaxel)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - 0 (Gemcitabine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Benzamides
MH  - Deoxycytidine/administration & dosage/analogs & derivatives
MH  - Diffusion Magnetic Resonance Imaging
MH  - Docetaxel
MH  - Drug Administration Schedule
MH  - Drug Interactions
MH  - *Drug Resistance, Neoplasm
MH  - Female
MH  - Humans
MH  - Imatinib Mesylate
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Michigan
MH  - Middle Aged
MH  - *Neoplasm Recurrence, Local
MH  - Neoplasms/*drug therapy/pathology
MH  - New Jersey
MH  - Perfusion Imaging
MH  - Piperazines/administration & dosage
MH  - Pyrimidines/administration & dosage
MH  - Taxoids/administration & dosage
MH  - Time Factors
MH  - Treatment Outcome
MH  - Gemcitabine
PMC - PMC5300057
MID - NIHMS836328
EDAT- 2010/08/11 06:00
MHDA- 2012/05/09 06:00
PMCR- 2017/02/09
CRDT- 2010/08/11 06:00
PHST- 2010/05/17 00:00 [received]
PHST- 2010/07/22 00:00 [accepted]
PHST- 2010/08/11 06:00 [entrez]
PHST- 2010/08/11 06:00 [pubmed]
PHST- 2012/05/09 06:00 [medline]
PHST- 2017/02/09 00:00 [pmc-release]
AID - 10.1007/s10637-010-9504-5 [doi]
PST - ppublish
SO  - Invest New Drugs. 2012 Feb;30(1):258-65. doi: 10.1007/s10637-010-9504-5. Epub 
      2010 Aug 10.