PMID- 20031390
OWN - NLM
STAT- MEDLINE
DCOM- 20100409
LR  - 20171116
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 46
IP  - 4
DP  - 2010 Mar
TI  - Evaluation of the safety of C-1311 (SYMADEX) administered in a phase 1 dose 
      escalation trial as a weekly infusion for 3 consecutive weeks in patients with 
      advanced solid tumours.
PG  - 729-34
LID - 10.1016/j.ejca.2009.12.005 [doi]
AB  - PURPOSE: C-1311 is a member of the novel imidazoacridinone family of anticancer 
      agents. This phase 1 trial was designed to investigate the safety, tolerability 
      and preliminary anti-tumour activity of C-1311. PATIENTS AND METHODS: This was a 
      phase 1, inter-subject dose escalating and pharmacokinetic study of intravenous 
      (IV) C-1311, administered weekly during 3consecutive weeks followed by 1week rest 
      (constituting 1 cycle) in subjects with advanced solid tumours. RESULTS: 
      Twenty-two (22) patients were treated with C-1311, the highest dose given was 
      640mg/m(2). All subjects experienced one or more treatment-related adverse events 
      (AEs). The most frequently observed treatment-related AEs were neutropaenia and 
      nausea (50% each), followed by vomiting (27%), anaemia (23%), asthenia (23%) and 
      diarrhoea (18%). Most treatment-related AEs were of Common Terminology Criteria 
      for Adverse Events (CTCAE) grades 1-2, except for the blood and lymphatic system 
      disorders, which were primarily of grades 3-4. The recommended dose (RD) of 
      C-1311 administered as once weekly IV infusions for 3weeks every 4weeks is 
      480mg/m(2), with the dose limiting toxicity (DLT) being grade 4 neutropaenia 
      lasting more than 7days. Treatment at this dose offers a predictable safety 
      profile and excellent tolerability. CONCLUSION: The safety profile and 
      preliminary anti-tumour efficacy of C-1311, observed in this broad-phase 
      dose-finding study, warrants further evaluation of the compound.
CI  - Copyright 2009 Elsevier Ltd. All rights reserved.
FAU - Isambert, N
AU  - Isambert N
AD  - Department of Medical Oncology, Centre Georges-Francois Leclerc, 1 rue du Pr 
      Marion, 21079 Dijon, France. nisambert@dijon.fnclcc.fr
FAU - Campone, M
AU  - Campone M
FAU - Bourbouloux, E
AU  - Bourbouloux E
FAU - Drouin, M
AU  - Drouin M
FAU - Major, A
AU  - Major A
FAU - Yin, W
AU  - Yin W
FAU - Loadman, P
AU  - Loadman P
FAU - Capizzi, R
AU  - Capizzi R
FAU - Grieshaber, C
AU  - Grieshaber C
FAU - Fumoleau, P
AU  - Fumoleau P
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20091222
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (Aminoacridines)
RN  - 0 (Antineoplastic Agents)
RN  - MZ4Y5H4OAB (C 1311)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Aged
MH  - Aminoacridines/administration & dosage/*adverse effects/blood
MH  - Antineoplastic Agents/administration & dosage/*adverse effects/blood
MH  - Biological Availability
MH  - Combined Modality Therapy
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Infusions, Intravenous
MH  - Male
MH  - Middle Aged
MH  - Neoplasms/blood/*drug therapy
MH  - Neutropenia/chemically induced
MH  - Treatment Outcome
EDAT- 2009/12/25 06:00
MHDA- 2010/04/10 06:00
CRDT- 2009/12/25 06:00
PHST- 2009/10/29 00:00 [received]
PHST- 2009/12/01 00:00 [accepted]
PHST- 2009/12/25 06:00 [entrez]
PHST- 2009/12/25 06:00 [pubmed]
PHST- 2010/04/10 06:00 [medline]
AID - S0959-8049(09)00917-4 [pii]
AID - 10.1016/j.ejca.2009.12.005 [doi]
PST - ppublish
SO  - Eur J Cancer. 2010 Mar;46(4):729-34. doi: 10.1016/j.ejca.2009.12.005. Epub 2009 
      Dec 22.