PMID- 16126736
OWN - NLM
STAT- MEDLINE
DCOM- 20060404
LR  - 20200203
IS  - 0923-7534 (Print)
IS  - 0923-7534 (Linking)
VI  - 16
IP  - 12
DP  - 2005 Dec
TI  - A phase I trial of liposomal doxorubicin, paclitaxel and valspodar (PSC-833), an 
      inhibitor of multidrug resistance.
PG  - 1968-73
AB  - PURPOSE: The aim of this study was to determine (i) the maximum tolerated dose 
      (MTD) of liposomal doxorubicin (L-DOX) and paclitaxel (DP), (ii) the MTD of DP 
      plus valspodar (DPV) and (iii) pharmacokinetic (PK) interactions of valspodar 
      with L-DOX and paclitaxel. METHODS: Twenty-three patients with metastatic cancers 
      received DP, followed 4 weeks later by DPV. Dose levels of DP were (mg/m2 for 
      L-DOX/paclitaxel): 30/135 (n = 7), 30/150 (n = 4), 35/150 (n = 8) and 40/150 (n = 
      4). Dose levels of DPV were 15/70 (n = 10) and 15/60 (n = 10). Serial, paired PK 
      studies were performed. RESULTS: The MTD of DP was 40/150. For DPV at 15/70, five 
      of 10 patients experienced grade 4 neutropenia. In the next cohort, a reduced 
      dose of 15/60 was well tolerated. Valspodar produced reversible grade 3 ataxia in 
      seven patients, requiring dose reduction from 5 to 4 mg/kg. Paired PK studies 
      indicated no interaction between L-DOX and valspodar, and a 49% increase in the 
      median half-life of paclitaxel. Two partial and one minor remissions were noted. 
      CONCLUSIONS: The use of valspodar necessitated dose reductions of DP, with 
      neutropenia being dose limiting. Valspodar PK interactions were observed with 
      paclitaxel but not L-DOX.
FAU - Advani, R
AU  - Advani R
AD  - Oncology Division, Stanford University Medical Center, Stanford, CA 94305-5151, 
      USA.
FAU - Lum, B L
AU  - Lum BL
FAU - Fisher, G A
AU  - Fisher GA
FAU - Halsey, J
AU  - Halsey J
FAU - Chin, D L
AU  - Chin DL
FAU - Jacobs, C D
AU  - Jacobs CD
FAU - Sikic, B I
AU  - Sikic BI
LA  - eng
GR  - M01 RR 00070/RR/NCRR NIH HHS/United States
GR  - R01 CA 52168/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20050826
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Cyclosporins)
RN  - 0 (Liposomes)
RN  - 80168379AG (Doxorubicin)
RN  - P88XT4IS4D (Paclitaxel)
RN  - Q7ZP55KF3X (valspodar)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage
MH  - Cohort Studies
MH  - Cyclosporins/administration & dosage
MH  - Dose-Response Relationship, Drug
MH  - Doxorubicin/administration & dosage
MH  - Drug Interactions
MH  - *Drug Resistance, Multiple
MH  - *Drug Resistance, Neoplasm
MH  - Female
MH  - Humans
MH  - Liposomes
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Neoplasms/*drug therapy/metabolism
MH  - Paclitaxel/administration & dosage
EDAT- 2005/08/30 09:00
MHDA- 2006/04/06 09:00
CRDT- 2005/08/30 09:00
PHST- 2005/08/30 09:00 [pubmed]
PHST- 2006/04/06 09:00 [medline]
PHST- 2005/08/30 09:00 [entrez]
AID - S0923-7534(19)47799-5 [pii]
AID - 10.1093/annonc/mdi396 [doi]
PST - ppublish
SO  - Ann Oncol. 2005 Dec;16(12):1968-73. doi: 10.1093/annonc/mdi396. Epub 2005 Aug 26.