Related Experiment Video
Updated: May 22, 2026
Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
Phase I study of saracatinib (AZD0530) in combination with paclitaxel and/or carboplatin in patients with solid
1Drug Development Unit, Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, UK. stan.kaye@rmh.nhs.uk
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.
