PURPOSE:Gemcitabine as a single agent and the combination of gemcitabine and docetaxel have activity in patients with metastatic soft tissue sarcoma. To determine if the addition of docetaxel to gemcitabine improved clinical outcome of patients with metastatic soft tissue sarcomas, we compared a fixed dose rate infusion of gemcitabine versus a lower dose of gemcitabine with docetaxel. PATIENTS AND METHODS: In this open-label phase II clinical trial, the primary end point was tumor response, defined as complete or partial response or stable disease lasting at least 24 weeks. A Bayesian adaptive randomization procedure was used to produce an imbalance in the randomization in favor of the superior treatment, accounting for treatment-subgroup interactions. RESULTS:One hundred nineteen of 122 randomly assigned patients had assessable outcomes. The adaptive randomization assigned 73 patients (60%) to gemcitabine-docetaxel and 49 patients (40%) to gemcitabine alone, indicating gemcitabine-docetaxel was superior. The objective Response Evaluation Criteria in Solid Tumors response rates were 16% (gemcitabine-docetaxel) and 8% (gemcitabine). Given the data, the posterior probabilities that gemcitabine-docetaxel was superior for progression-free and overall survival were 0.98 and 0.97, respectively. Median progression-free survival was 6.2 months for gemcitabine-docetaxel and 3.0 months for gemcitabine alone; median overall survival was 17.9 months for gemcitabine-docetaxel and 11.5 months for gemcitabine. The posterior probability that patients receiving gemcitabine-docetaxel had a shorter time to discontinuation for toxicity compared with gemcitabine alone was .999. CONCLUSION:Gemcitabine-docetaxel yielded superior progression-free and overall survival to gemcitabine alone, but with increased toxicity. Adaptive randomization is an effective method to reduce the number of patients receiving inferior therapy.
RCT Entities:
PURPOSE:Gemcitabine as a single agent and the combination of gemcitabine and docetaxel have activity in patients with metastatic soft tissue sarcoma. To determine if the addition of docetaxel to gemcitabine improved clinical outcome of patients with metastatic soft tissue sarcomas, we compared a fixed dose rate infusion of gemcitabine versus a lower dose of gemcitabine with docetaxel. PATIENTS AND METHODS: In this open-label phase II clinical trial, the primary end point was tumor response, defined as complete or partial response or stable disease lasting at least 24 weeks. A Bayesian adaptive randomization procedure was used to produce an imbalance in the randomization in favor of the superior treatment, accounting for treatment-subgroup interactions. RESULTS: One hundred nineteen of 122 randomly assigned patients had assessable outcomes. The adaptive randomization assigned 73 patients (60%) to gemcitabine-docetaxel and 49 patients (40%) to gemcitabine alone, indicating gemcitabine-docetaxel was superior. The objective Response Evaluation Criteria in Solid Tumors response rates were 16% (gemcitabine-docetaxel) and 8% (gemcitabine). Given the data, the posterior probabilities that gemcitabine-docetaxel was superior for progression-free and overall survival were 0.98 and 0.97, respectively. Median progression-free survival was 6.2 months for gemcitabine-docetaxel and 3.0 months for gemcitabine alone; median overall survival was 17.9 months for gemcitabine-docetaxel and 11.5 months for gemcitabine. The posterior probability that patients receiving gemcitabine-docetaxel had a shorter time to discontinuation for toxicity compared with gemcitabine alone was .999. CONCLUSION:Gemcitabine-docetaxel yielded superior progression-free and overall survival to gemcitabine alone, but with increased toxicity. Adaptive randomization is an effective method to reduce the number of patients receiving inferior therapy.
Authors: Christopher W Ryan; Chacon Matias; Mark Agulnik; Antonio Lopez-Pousa; Charles Williams; Dinesh P de Alwis; Christopher Kaiser; Mary Alice Miller; Sabine Ermisch; Robert Ilaria; M L Keohan Journal: Invest New Drugs Date: 2012-04-27 Impact factor: 3.850
Authors: Oliver Zivanovic; Lindsay M Jacks; Alexia Iasonos; Mario M Leitao; Robert A Soslow; Emanuela Veras; Dennis S Chi; Nadeem R Abu-Rustum; Richard R Barakat; Murray F Brennan; Martee L Hensley Journal: Cancer Date: 2011-07-12 Impact factor: 6.860
Authors: Ya Zhang; Jingqing Yang; Na Zhao; Cao Wang; Santosh Kamar; Yonghong Zhou; Zewei He; Jifei Yang; Bin Sun; Xiaoqian Shi; Lei Han; Zuozhang Yang Journal: Oncol Lett Date: 2018-09-12 Impact factor: 2.967
Authors: Jérôme Fayette; Nicolas Penel; Christine Chevreau; Jean-Yves Blay; Didier Cupissol; Antoine Thyss; Cécile Guillemet; Maria Rios; Frédéric Rolland; Pierre Fargeot; Jacques Olivier Bay; Simone Mathoulin-Pelissier; Jean Michel Coindre; Binh Bui-Nguyen Journal: Invest New Drugs Date: 2009-01-16 Impact factor: 3.850
Authors: Martina Zemanova; Katarina Machalekova; Monika Sandorova; Elena Boljesikova; Marta Skultetyova; Juraj Svec; Andrej Zeman Journal: Rep Pract Oncol Radiother Date: 2013-08-23