PMID- 15367419
OWN - NLM
STAT- MEDLINE
DCOM- 20050114
LR  - 20200203
IS  - 0923-7534 (Print)
IS  - 0923-7534 (Linking)
VI  - 15
IP  - 10
DP  - 2004 Oct
TI  - Weekly paclitaxel combined with pegylated liposomal doxorubicin (CaelyxTM) given 
      every 4 weeks: dose-finding and pharmacokinetic study in patients with advanced 
      solid tumors.
PG  - 1566-73
AB  - BACKGROUND: We aimed to define the maximum tolerated dose (MTD) and characterize 
      the toxicity of the combination of pegylated liposomal doxorubicin (PLD; Caelyx 
      trade mark ) and weekly paclitaxel (wPTX), and to investigate pharmacokinetics of 
      PLD in this combination. METHODS: A phase I study was performed with an initial 
      dose of 50 mg/m(2) wPTX and 30 mg/m(2) PLD. The paclitaxel dose was escalated in 
      increments of 10 mg/m(2) and PLD in increments of 5 mg/m(2) until the MTD was 
      reached. The pharmacokinetics of PLD were studied at the highest achieved dose 
      levels. RESULTS: Forty-four cancer patients were enrolled. The MTD was 30/90 and 
      35/80 mg/m(2) for PLD/wPTX. Dose-limiting toxicities included treatment delay for 
      neutropenia grade 3, febrile neutropenia, palmar-plantar erythrodysesthesia and 
      deep venous thrombosis. Toxicity below the MTD was mild: skin toxicity grade 1-2 
      developed at high cumulative doses and vascular thrombotic events occurred in two 
      patients with predisposing factors. No cardiotoxicity or clinically relevant 
      peripheral neuropathy was seen. Nausea/vomiting and alopecia were negligible. 
      Three complete responses and nine partial responses were documented among 34 
      evaluable cases. PLD plasma concentrations were evaluated in seven patients 
      treated at subMTD. Paclitaxel produced a median 53.5% increase of PLD area under 
      the concentration curve (range 4.4%-219%). CONCLUSIONS: The combination of 
      PLD/wPTX constitutes an active chemotherapy regimen with mild toxicity that 
      merits investigation in phase II at 30/80 or 35/70 mg/m(2). Patients should be 
      monitored for a potentially increased risk of thromboembolic events.
FAU - Briasoulis, E
AU  - Briasoulis E
AD  - Department of Medical Oncology, University of Ioannina, Ioannina, Greece. 
      briasou@otenet.gr
FAU - Pentheroudakis, G
AU  - Pentheroudakis G
FAU - Karavasilis, V
AU  - Karavasilis V
FAU - Tzamakou, E
AU  - Tzamakou E
FAU - Rammou, D
AU  - Rammou D
FAU - Pavlidis, N
AU  - Pavlidis N
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase I
PT  - Journal Article
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Liposomes)
RN  - 80168379AG (Doxorubicin)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/*adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Doxorubicin/administration & dosage/adverse effects/pharmacokinetics
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Liposomes
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasms/*drug therapy
MH  - Neutropenia/chemically induced
MH  - Paclitaxel/administration & dosage/adverse effects/pharmacokinetics
EDAT- 2004/09/16 05:00
MHDA- 2005/01/15 09:00
CRDT- 2004/09/16 05:00
PHST- 2004/09/16 05:00 [pubmed]
PHST- 2005/01/15 09:00 [medline]
PHST- 2004/09/16 05:00 [entrez]
AID - S0923-7534(19)51058-4 [pii]
AID - 10.1093/annonc/mdh404 [doi]
PST - ppublish
SO  - Ann Oncol. 2004 Oct;15(10):1566-73. doi: 10.1093/annonc/mdh404.