PMID- 17986625
OWN - NLM
STAT- MEDLINE
DCOM- 20080318
LR  - 20201209
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Linking)
VI  - 19
IP  - 2
DP  - 2008 Feb
TI  - A phase Ib dose-escalation study of erlotinib, capecitabine and oxaliplatin in 
      metastatic colorectal cancer patients.
PG  - 332-9
AB  - BACKGROUND: Dysregulation of the epidermal growth factor receptor (HER1/EGFR) has 
      been reported in colorectal cancer (CRC). Erlotinib is a potent inhibitor of 
      HER1/EGFR-mediated signaling. This trial of patients with metastatic CRC (MCRC) 
      examined the safety, maximum tolerated dose (MTD) and pharmacokinetics (PK) of 
      erlotinib in combination with capecitabine and oxaliplatin (XELOX), a regimen 
      with established efficacy. PATIENTS AND METHODS: Patients previously untreated or 
      treated with one line of 5-fluorouracil and/or irinotecan received escalating 
      oral doses of erlotinib (daily), capecitabine (days 1-14) and i.v. oxaliplatin 
      (day 1 of a 21-day cycle). RESULTS: The first six patients in cohort 1 (erlotinib 
      100 mg/day, capecitabine 825 mg/m(2) twice daily, oxaliplatin 130 mg/m(2)) had no 
      dose-limiting toxicities (DLTs). In cohort 2 (capecitabine increased to 1000 
      mg/m(2) twice daily), two of six patients had DLTs. When cohort 2 was expanded to 
      11 patients two further DLTs occurred, exceeding the definition of MTD. Cohort 1 
      was expanded to 12 patients, and no DLTs occurred. The most common adverse events 
      (AEs) were diarrhea and rash. There was a trend for reduced capecitabine 
      concentrations in the presence of erlotinib. While this was not statistically 
      significant, the possibility of an interaction affecting capecitabine PK cannot 
      be excluded. Antitumor activity was observed in both cohorts (one complete and 
      four partial responses, and stable disease in 11 patients). CONCLUSION: The MTD 
      for this combination in MCRC is capecitabine 825 mg/m(2) twice daily days 1-14, 
      oxaliplatin 130 mg/m(2) day 1 and erlotinib 100 mg/day of a 21-day cycle. The 
      combination was well tolerated at the MTD, with no unexpected AEs. The use of 
      this combination in MCRC warrants further investigation.
FAU - Van Cutsem, E
AU  - Van Cutsem E
AD  - University Hospital Gasthuisberg, Leuven, Belgium. 
      eric.vancutsem@uz.kuleuven.ac.be
FAU - Verslype, C
AU  - Verslype C
FAU - Beale, P
AU  - Beale P
FAU - Clarke, S
AU  - Clarke S
FAU - Bugat, R
AU  - Bugat R
FAU - Rakhit, A
AU  - Rakhit A
FAU - Fettner, S H
AU  - Fettner SH
FAU - Brennscheidt, U
AU  - Brennscheidt U
FAU - Feyereislova, A
AU  - Feyereislova A
FAU - Delord, J-P
AU  - Delord JP
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20071106
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Drug Combinations)
RN  - 0 (Organoplatinum Compounds)
RN  - 0 (Oxaloacetates)
RN  - 0 (Quinazolines)
RN  - 04ZR38536J (Oxaliplatin)
RN  - 0W860991D6 (Deoxycytidine)
RN  - 6804DJ8Z9U (Capecitabine)
RN  - DA87705X9K (Erlotinib Hydrochloride)
RN  - U3P01618RT (Fluorouracil)
RN  - XELOX
SB  - IM
MH  - Adenocarcinoma/*drug therapy/mortality/*secondary
MH  - Administration, Oral
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols
MH  - Capecitabine
MH  - Colorectal Neoplasms/*drug therapy/mortality/*pathology
MH  - Deoxycytidine/administration & dosage/adverse effects/*analogs & derivatives
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Drug Combinations
MH  - Erlotinib Hydrochloride
MH  - Female
MH  - Fluorouracil/administration & dosage/adverse effects/*analogs & derivatives
MH  - Follow-Up Studies
MH  - Humans
MH  - Infusions, Intravenous
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Neoplasm Staging
MH  - Organoplatinum Compounds/*administration & dosage/*adverse effects
MH  - Oxaliplatin
MH  - Oxaloacetates
MH  - Quinazolines/administration & dosage/adverse effects
MH  - Risk Assessment
MH  - Survival Analysis
MH  - Treatment Outcome
EDAT- 2007/11/08 09:00
MHDA- 2008/03/19 09:00
CRDT- 2007/11/08 09:00
PHST- 2007/11/08 09:00 [pubmed]
PHST- 2008/03/19 09:00 [medline]
PHST- 2007/11/08 09:00 [entrez]
AID - S0923-7534(19)41329-X [pii]
AID - 10.1093/annonc/mdm452 [doi]
PST - ppublish
SO  - Ann Oncol. 2008 Feb;19(2):332-9. doi: 10.1093/annonc/mdm452. Epub 2007 Nov 6.