PMID- 21931969
OWN - NLM
STAT- MEDLINE
DCOM- 20130403
LR  - 20211020
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Linking)
VI  - 30
IP  - 5
DP  - 2012 Oct
TI  - Phase I combination study of trabectedin and capecitabine in patients with 
      advanced malignancies.
PG  - 1942-9
LID - 10.1007/s10637-011-9747-9 [doi]
AB  - BACKGROUND: To determine the maximum tolerated dose (MTD), safety and 
      pharmacokinetics of trabectedin with capecitabine in patients with advanced 
      malignancies. DESIGN: In this Phase I, open-label, dose-finding study, patients 
      refractory to standard therapy received trabectedin (3-h intravenous infusion, 
      0.4-1.3 mg/m(2), day 1) and capecitabine (2,000 or 1,600 mg/m(2)/day orally, days 
      2-15) every 3 weeks. Standard "3 + 3" dose escalation was used to define the MTD. 
      Antitumor response was assessed every two cycles; adverse events (AEs) were 
      recorded throughout. RESULTS: Forty patients received 149 cycles of treatment 
      (median 2; range 1-11) at nine dose levels. Gastrointestinal dose-limiting 
      toxicities in two patients at two dose levels with capecitabine at 2,000 
      mg/m(2)/day prompted dose reduction to 1,600 mg/m(2)/day and initiation of new 
      trabectedin dose escalation at 0.6 mg/m(2). The MTD was capecitabine 1,600 
      mg/m(2)/day + trabectedin 1.1 mg/m(2). Common grade 3-4 drug-related AEs were 
      neutropenia (20%), nausea (18%), diarrhea (15%) and palmar-plantar 
      erythrodysesthesia (15%). One patient with cholangiocarcinoma achieved a 
      sustained partial response, and 18 patients maintained stable disease (six for >/=6 
      months). CONCLUSIONS: The combination of trabectedin and capecitabine is 
      generally well tolerated, without pharmacokinetic interactions, and shows some 
      activity in patients with advanced cancers.
FAU - Gore, Lia
AU  - Gore L
AD  - University of Colorado Cancer Center, Aurora, CO 80045, USA. 
      lia.gore@ucdenver.edu
FAU - Rivera, E
AU  - Rivera E
FAU - Basche, M
AU  - Basche M
FAU - Moulder-Thompson, S L
AU  - Moulder-Thompson SL
FAU - Li, J
AU  - Li J
FAU - Eppers, S
AU  - Eppers S
FAU - Grolnic, S
AU  - Grolnic S
FAU - O'Bryant, C
AU  - O'Bryant C
FAU - Cleere, D
AU  - Cleere D
FAU - Elsayed, Y A
AU  - Elsayed YA
FAU - Eckhardt, S G
AU  - Eckhardt SG
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20110920
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Dioxoles)
RN  - 0 (Tetrahydroisoquinolines)
RN  - 0W860991D6 (Deoxycytidine)
RN  - 6804DJ8Z9U (Capecitabine)
RN  - ID0YZQ2TCP (Trabectedin)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/*adverse 
      effects/pharmacokinetics
MH  - Capecitabine
MH  - Deoxycytidine/administration & dosage/adverse effects/analogs & 
      derivatives/pharmacokinetics
MH  - Dioxoles/administration & dosage/adverse effects/pharmacokinetics
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Female
MH  - Fluorouracil/administration & dosage/adverse effects/analogs & 
      derivatives/pharmacokinetics
MH  - Humans
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasms/*drug therapy/metabolism
MH  - Tetrahydroisoquinolines/administration & dosage/adverse effects/pharmacokinetics
MH  - Trabectedin
MH  - Young Adult
EDAT- 2011/09/21 06:00
MHDA- 2013/04/04 06:00
CRDT- 2011/09/21 06:00
PHST- 2011/06/23 00:00 [received]
PHST- 2011/08/30 00:00 [accepted]
PHST- 2011/09/21 06:00 [entrez]
PHST- 2011/09/21 06:00 [pubmed]
PHST- 2013/04/04 06:00 [medline]
AID - 10.1007/s10637-011-9747-9 [doi]
PST - ppublish
SO  - Invest New Drugs. 2012 Oct;30(5):1942-9. doi: 10.1007/s10637-011-9747-9. Epub 
      2011 Sep 20.