PMID- 22531637
OWN - NLM
STAT- MEDLINE
DCOM- 20120723
LR  - 20211021
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 106
IP  - 11
DP  - 2012 May 22
TI  - Phase I study of saracatinib (AZD0530) in combination with paclitaxel and/or 
      carboplatin in patients with solid tumours.
PG  - 1728-34
LID - 10.1038/bjc.2012.158 [doi]
AB  - BACKGROUND: As a prelude to combination studies aimed at resistance reversal, 
      this dose-escalation/dose-expansion study investigated the selective Src kinase 
      inhibitor saracatinib (AZD0530) in combination with carboplatin and/or 
      paclitaxel. METHODS: Patients with advanced solid tumours received saracatinib 
      once-daily oral tablets in combination with either carboplatin AUC 5 every 3 
      weeks (q3w), paclitaxel 175 mg m(-2) q3w, paclitaxel 80 mg m(-2) every 1 week 
      (q1w), or carboplatin AUC 5 plus paclitaxel 175 mg m(-2) q3w. The primary 
      endpoint was safety/tolerability. RESULTS: A total of 116 patients received 
      saracatinib 125 (N=20), 175 (N=44), 225 (N=40), 250 (N=9), or 300 mg (N=3). There 
      were no clear dose-related trends within each chemotherapy regimen group in 
      number or severity of adverse events (AEs). However, combining all groups, the 
      occurrence of grade >/=3 asthenic AEs (all causality) was dose-related (125 mg, 
      10%; 175 mg, 20%; >/=225 mg, 33%), and grade >/=3 neutropenia occurred more commonly 
      at doses >/=225 mg. There was no evidence that saracatinib affected exposure to 
      carboplatin or paclitaxel, or vice versa. Objective responses were seen in 5 out 
      of 44 patients (11%) receiving carboplatin plus paclitaxel q3w, and 5 out of 24 
      (21%) receiving paclitaxel q1w. CONCLUSION: Saracatinib doses up to 175 mg with 
      paclitaxel with/without carboplatin showed acceptable toxicity in most patients, 
      and are suitable for further trials.
CI  - (c) 2012 Cancer Research UK
FAU - Kaye, S
AU  - Kaye S
AD  - Drug Development Unit, Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 
      5PT, UK. stan.kaye@rmh.nhs.uk
FAU - Aamdal, S
AU  - Aamdal S
FAU - Jones, R
AU  - Jones R
FAU - Freyer, G
AU  - Freyer G
FAU - Pujade-Lauraine, E
AU  - Pujade-Lauraine E
FAU - de Vries, E G E
AU  - de Vries EG
FAU - Barriuso, J
AU  - Barriuso J
FAU - Sandhu, S
AU  - Sandhu S
FAU - Tan, D S-W
AU  - Tan DS
FAU - Hartog, V
AU  - Hartog V
FAU - Kuenen, B
AU  - Kuenen B
FAU - Ruijter, R
AU  - Ruijter R
FAU - Kristensen, G B
AU  - Kristensen GB
FAU - Nyakas, M
AU  - Nyakas M
FAU - Barrett, S
AU  - Barrett S
FAU - Burke, W
AU  - Burke W
FAU - Pietersma, D
AU  - Pietersma D
FAU - Stuart, M
AU  - Stuart M
FAU - Emeribe, U
AU  - Emeribe U
FAU - Boven, E
AU  - Boven E
LA  - eng
GR  - Cancer Research UK/United Kingdom
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20120424
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Benzodioxoles)
RN  - 0 (Quinazolines)
RN  - 9KD24QGH76 (saracatinib)
RN  - BG3F62OND5 (Carboplatin)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Benzodioxoles/*administration & dosage/adverse effects
MH  - Carboplatin/administration & dosage/adverse effects
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neoplasms/*drug therapy
MH  - Paclitaxel/administration & dosage/adverse effects
MH  - Quinazolines/*administration & dosage/adverse effects
PMC - PMC3364128
COIS- MS, DP, WB, and UE are employees of AstraZeneca, and MS holds stock in 
      AstraZeneca. SK, GK, RJ, and EP-L have received remuneration for consulting 
      and/or advisory board attendance from AstraZeneca. RJ has received research 
      support from AstraZeneca. MN has received an honorarium for lecturing from 
      Bristol Myers Squibb, and EB has received research funding from Roche. SA, GF, 
      EdV, JB, SS, DT, VH, BK, RR, and SB have no potential conflicts of interest to 
      declare.
EDAT- 2012/04/26 06:00
MHDA- 2012/07/24 06:00
PMCR- 2013/05/22
CRDT- 2012/04/26 06:00
PHST- 2012/04/26 06:00 [entrez]
PHST- 2012/04/26 06:00 [pubmed]
PHST- 2012/07/24 06:00 [medline]
PHST- 2013/05/22 00:00 [pmc-release]
AID - bjc2012158 [pii]
AID - 10.1038/bjc.2012.158 [doi]
PST - ppublish
SO  - Br J Cancer. 2012 May 22;106(11):1728-34. doi: 10.1038/bjc.2012.158. Epub 2012 
      Apr 24.