European Journal of Cancer .Volume 56, March 2016, Pages 122–130 .
Nobuhito Arakia, , , Shunji Takahashib, Hideshi Sugiurac, d, Takafumi Uedae, Tsukasa Yonemotof, Mitsuru Takahashig, Hideo Moriokah, Hiroaki Hiragai, Toru Hirumaj, Toshiyuki Kunisadak, Akihiko Matsuminel, Akira Kawaim .
Highlights
• We report a retrospective comparison of a randomised study and crossover study.
• Median progression-free survival (PFS) of best supportive care arm was dramatically improved by crossing over to trabectedin.
• 86% of patients had growth modulation index ≥1.33, which means ≥33% time to progression improvement by trabectedin.
• The trend of prolongation of PFS by crossover seemed clear in patients with myxoid/round cell liposarcoma.
• The safety profile of trabectedin was similar to that in the randomised study.
Abstract
Aim
Our randomised phase II study showed the clinical benefit of trabectedin compared with best supportive care (BSC) in patients with advanced translocation-related sarcomas after the failure of standard chemotherapy. The aim of the present study was to evaluate efficacy and safety of trabectedin in the identical patients crossed over to trabectedin after disease progression in the BSC arm of the randomised study.
Patients and methods
This was a single-arm study of the BSC patients of the randomised study in whom disease progressed. Trabectedin (1.2 mg/m2) was administered over 24 h on day 1 of a 21-d treatment cycle. The efficacy and safety of trabectedin after BSC were evaluated and retrospectively compared with the results of the randomised study.
Results
Thirty patients crossed over to trabectedin. Median progression-free survival (PFS) was 7.3 months (95% confidence interval [CI]: 2.9–9.1) after crossover compared with 0.9 months (95% CI: 0.9–1.0) at BSC in the randomised study. PFS in the present study was comparable to that of the trabectedin arm in the randomised study. The number of patients with growth modulation index ≥1.33 was 25 (86%). Individual tumour volume was decreased in 11 patients after crossover. Adverse drug reactions (ADRs) were observed in 27 patients (96.4%). ADRs of grade III–IV were mainly bone marrow suppression and abnormal liver functions.
Conclusion
Trabectedin was revealed to be effective and well tolerated in the identical patients crossed over to trabectedin after disease progression in BSC.
The present study is registered with the Japan Pharmaceutical Information Center, number JapicCTI-121853.
