PMID- 18607882
OWN - NLM
STAT- MEDLINE
DCOM- 20090121
LR  - 20131121
IS  - 1651-226X (Electronic)
IS  - 0284-186X (Linking)
VI  - 48
IP  - 1
DP  - 2009
TI  - Intravenous administration of CP-4055 (ELACYT) in patients with solid tumours. A 
      Phase I study.
PG  - 137-45
LID - 10.1080/02841860802183620 [doi]
AB  - PURPOSE: Cytarabine (ara-C) has limited activity in solid tumours. CP-4055 
      (ELACYT) is a novel ara-C-5'-elaidic acid ester that may circumvent this 
      limitation. CP-4055 maximum tolerated dose (MTD), pharmacokinetics and antitumor 
      activity have been investigated in patients with solid tumours. MATERIAL AND 
      METHODS: Thirty-four patients (19 malignant melanoma, 8 ovarian cancers and 7 
      NSCLC) received CP-4055 as a 30 min, or 2 hr intravenous (IV) infusion daily for 
      5 consecutive days every 3 or 4 weeks (D1-5 q3w or D1-5 q4w) in a dose escalation 
      designed study with doses ranging from 30 to 240 mg/m(2)/day. RESULTS: The most 
      frequent CTC grade 1-2 adverse events (AEs) were nausea, fatigue, vomiting, 
      anorexia and pyrexia. Most of the grade 3-4 AEs were neutropenia. The MTD was 200 
      mg/m(2)/day and 240 mg/m(2)/day for D1-5 q3w and D1-5 q4w, respectively. The MTD 
      was independent of infusion time in the 4 week schedule. CP-4055 was maintained 
      in plasma for up to 5-10 hr at dose levels >150 mg/m(2)/day. One objective 
      partial response (PR) with time to progression (TTP) of 22 months was reported in 
      an advanced malignant melanoma patient. CONCLUSION: CP-4055 was well tolerated; 
      the majority of the AEs were of CTC grade 1. The 3 week schedule was not 
      recommended due to neutropenic nadir between days 18-26. The recommended dose was 
      200 mg/m(2)/day in a D1-5 q4w schedule. Efficacy data suggest that CP-4055 might 
      be active in treatment of solid tumours.
FAU - Dueland, Svein
AU  - Dueland S
AD  - Department of Clinical Cancer Research, The Norwegian Radium Hospital, Oslo, 
      Norway.
FAU - Aamdal, Steinar
AU  - Aamdal S
FAU - Lind, Michael J
AU  - Lind MJ
FAU - Thomas, Hilary
AU  - Thomas H
FAU - Sandvold, Marit Liland
AU  - Sandvold ML
FAU - Gaullier, Jean-Michel
AU  - Gaullier JM
FAU - Rasch, Wenche
AU  - Rasch W
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PL  - Sweden
TA  - Acta Oncol
JT  - Acta oncologica (Stockholm, Sweden)
JID - 8709065
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 04079A1RDZ (Cytarabine)
RN  - 101235-34-1 (5'-oleoyl cytarabine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antimetabolites, Antineoplastic/*administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Carcinoma, Non-Small-Cell Lung/drug therapy/metabolism
MH  - Cytarabine/administration & dosage/adverse effects/*analogs & 
      derivatives/pharmacokinetics
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Infusions, Intravenous
MH  - Lung Neoplasms/drug therapy/metabolism
MH  - Melanoma/drug therapy/metabolism
MH  - Middle Aged
MH  - Neoplasms/*drug therapy/metabolism
MH  - Ovarian Neoplasms/drug therapy/metabolism
EDAT- 2008/07/09 09:00
MHDA- 2009/01/22 09:00
CRDT- 2008/07/09 09:00
PHST- 2008/07/09 09:00 [pubmed]
PHST- 2009/01/22 09:00 [medline]
PHST- 2008/07/09 09:00 [entrez]
AID - 794209009 [pii]
AID - 10.1080/02841860802183620 [doi]
PST - ppublish
SO  - Acta Oncol. 2009;48(1):137-45. doi: 10.1080/02841860802183620.