Abstract
The combination of trabectedin (T) and doxorubicin (D) was brought into clinical development
in soft tissue sarcoma (STS) and advanced breast cancer (ABC) because of its in vitro and in vivo additive anti-tumour effect, the fact that there are no overlapping toxicities and
the anti-tumour activity of T in those tumours. Feasibility and anti-tumour activity
of T+D administered every 3 weeks were evaluated in 38 patients (STS=29, ABC=9) untreated
for advanced disease. D was given at 60 mg/m2 and T at escalating doses from 600 to 800 μg/m2, which was the maximum tolerated dose due to dose-limiting febrile neutropenia and
asthenia. The recommended dose - given to 18 patients in total - was 700 μg/m2 T with 60 mg/m2 D. The pharmacokinetic profile of T and D at cycle 1 was analysed in 20 patients.
The most common toxicities included a severe but reversible ASAT/ALAT increase (94%),
nausea/vomiting, neutropenia, asthenia/fatigue, stomatitis. Partial response and stable
disease were assessed in 18% and 56% of STS patients and in 55% and 33% of ABC patients.
No pharmacokinetic interaction between T and D was observed. The lack of cumulative
toxicity and related complications and the promising activity in STS support further
development of T+D.
Keywords
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Article info
Publication history
Published online: December 29, 2008
Accepted:
November 13,
2008
Received in revised form:
September 15,
2008
Received:
July 7,
2008
Identification
Copyright
© 2008 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
