PMID- 19294387
OWN - NLM
STAT- MEDLINE
DCOM- 20090917
LR  - 20220330
IS  - 1432-0843 (Electronic)
IS  - 0344-5704 (Linking)
VI  - 64
IP  - 6
DP  - 2009 Nov
TI  - A randomized, phase II, dose-finding study of the pan-ErbB receptor 
      tyrosine-kinase inhibitor CI-1033 in patients with pretreated metastatic breast 
      cancer.
PG  - 1139-48
LID - 10.1007/s00280-009-0975-z [doi]
AB  - PURPOSE: To evaluate the efficacy and safety of the pan-ErbB receptor 
      tyrosine-kinase inhibitor CI-1033 in metastatic breast cancer (MBC). EXPERIMENTAL 
      DESIGN: Patients with measurable, progressive, or recurrent MBC whose primary 
      tumor expressed > or =1 ErbB receptor were randomized to the following CI-1033 
      regimens: 50 mg (arm A) or 150 mg (arm B) daily without rest period, or 450 
      mg/day x 14 days every 21 days (arm C). The primary endpoint was 1-year 
      progression-free survival (PFS). RESULTS: Overall, 194 patients were treated. 
      One-year PFS estimates were 3.8, 2.0, and 4.6%; median PFS was 61, 56, and 58 
      days; and investigator-assessed overall response rates were 1.5, 1.5, and 7.3%, 
      in arms A, B, and C, respectively. Response duration was 110-419 days. In arm C, 
      response (18.8 vs. 2.6%) and 1-year overall survival rates (86.7 vs. 47.5%) were 
      greater in patients with HER2-positive versus HER2-negative tumors. The incidence 
      of grade 3/4 adverse events (AEs) was dose-dependent, affecting 10.3, 48.6, and 
      80.4% of patients in arms A, B and C, respectively. The most common grade 3/4, 
      treatment-related AEs were diarrhea, asthenia, and stomatitis. Arm C enrollment 
      was prematurely discontinued due to a high frequency of grade 3/4 AEs. 
      CONCLUSION: Single-agent CI-1033 did not show clinically meaningful activity in 
      heavily pretreated patients with MBC expressing > or =1 ErbB receptor. Antitumor 
      activity was observed in arm C patients with HER2-positive tumors. However, only 
      the 50 mg dose was well tolerated, and the highest dose reached unacceptable 
      levels of toxicity.
FAU - Rixe, Olivier
AU  - Rixe O
AD  - Hopital de la Pitie Salpetriere, APHP, Paris, France. rixeo@mail.nih.gov
FAU - Franco, Sandra X
AU  - Franco SX
FAU - Yardley, Denise A
AU  - Yardley DA
FAU - Johnston, Stephen R
AU  - Johnston SR
FAU - Martin, Miguel
AU  - Martin M
FAU - Arun, Banu K
AU  - Arun BK
FAU - Letrent, Stephen P
AU  - Letrent SP
FAU - Rugo, Hope S
AU  - Rugo HS
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20090318
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Morpholines)
RN  - 0 (Receptors, Estrogen)
RN  - C78W1K5ASF (Canertinib)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (ERBB4 protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 2.7.10.1 (Receptor, ErbB-3)
RN  - EC 2.7.10.1 (Receptor, ErbB-4)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Breast Neoplasms/*drug therapy/metabolism/*pathology
MH  - Disease-Free Survival
MH  - ErbB Receptors/antagonists & inhibitors/metabolism
MH  - Female
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Middle Aged
MH  - Morpholines/*administration & dosage/adverse effects/*therapeutic use
MH  - *Neoplasm Metastasis/drug therapy
MH  - Receptor, ErbB-2/antagonists & inhibitors/metabolism
MH  - Receptor, ErbB-3/metabolism
MH  - Receptor, ErbB-4
MH  - Receptors, Estrogen/metabolism
MH  - Treatment Outcome
EDAT- 2009/03/19 09:00
MHDA- 2009/09/18 06:00
CRDT- 2009/03/19 09:00
PHST- 2008/10/22 00:00 [received]
PHST- 2009/03/02 00:00 [accepted]
PHST- 2009/03/19 09:00 [entrez]
PHST- 2009/03/19 09:00 [pubmed]
PHST- 2009/09/18 06:00 [medline]
AID - 10.1007/s00280-009-0975-z [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2009 Nov;64(6):1139-48. doi: 
      10.1007/s00280-009-0975-z. Epub 2009 Mar 18.