Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial
Beatrice Seddon,Sandra J. Strauss,Jeremy Whelan,Michael F. Leahy,Penella J. Woll,Fiona Cowie,Christian Rothermundt,Zoe Wood,Charlotte Benson,Nasim Ali,Maria Marples,Gareth J. Veal,David Jamieson,Katja Küver,Roberto Tirabosco,Sharon Forsyth,Stephen Nash,Hakim-Moulay Dehbi,Sandy Beare +18 more
TLDR
This study compared gemcitabine and docetaxel versus doxorubicin as first-line treatment for advanced or metastatic soft-tissue sarcoma and found that the proportion of patients alive and progression free at 24 weeks in the intention-to-treat population did not differ.Abstract:
Summary Background For many years, first-line treatment for locally advanced or metastatic soft-tissue sarcoma has been doxorubicin. This study compared gemcitabine and docetaxel versus doxorubicin as first-line treatment for advanced or metastatic soft-tissue sarcoma. Methods The GeDDiS trial was a randomised controlled phase 3 trial done in 24 UK hospitals and one Swiss Group for Clinical Cancer Research (SAKK) hospital. Eligible patients had histologically confirmed locally advanced or metastatic soft-tissue sarcoma of Trojani grade 2 or 3, disease progression before enrolment, and no previous chemotherapy for sarcoma or previous doxorubicin for any cancer. Patients were randomly assigned 1:1 to receive six cycles of intravenous doxorubicin 75 mg/m 2 on day 1 every 3 weeks, or intravenous gemcitabine 675 mg/m 2 on days 1 and 8 and intravenous docetaxel 75 mg/m 2 on day 8 every 3 weeks. Treatment was assigned using a minimisation algorithm incorporating a random element. Randomisation was stratified by age (≤18 years vs >18 years) and histological subtype. The primary endpoint was the proportion of patients alive and progression free at 24 weeks in the intention-to-treat population. Adherence to treatment and toxicity were analysed in the safety population, consisting of all patients who received at least one dose of their randomised treatment. The trial was registered with the European Clinical Trials (EudraCT) database (no 2009–014907–29) and with the International Standard Randomised Controlled Trial registry (ISRCTN07742377), and is now closed to patient entry. Findings Between Dec 3, 2010, and Jan 20, 2014, 257 patients were enrolled and randomly assigned to the two treatment groups (129 to doxorubicin and 128 to gemcitabine and docetaxel). Median follow-up was 22 months (IQR 15·7–29·3). The proportion of patients alive and progression free at 24 weeks did not differ between those who received doxorubicin versus those who received gemcitabine and docetaxel (46·3% [95% CI 37·5–54·6] vs 46·4% [37·5–54·8]); median progression-free survival (23·3 weeks [95% CI 19·6–30·4] vs 23·7 weeks [18·1–20·0]; hazard ratio [HR] for progression-free survival 1·28, 95% CI 0·99–1·65, p=0·06). The most common grade 3 and 4 adverse events were neutropenia (32 [25%] of 128 patients who received doxorubicin and 25 [20%] of 126 patients who received gemcitabine and docetaxel), febrile neutropenia (26 [20%] and 15 [12%]), fatigue (eight [6%] and 17 [14%]), oral mucositis (18 [14%] and two [2%]), and pain (ten [8%] and 13 [10%]). The three most common serious adverse events, representing 111 (39%) of all 285 serious adverse events recorded, were febrile neutropenia (27 [17%] of 155 serious adverse events in patients who received doxorubicin and 15 [12%] of 130 serious adverse events in patients who received gemcitabine and docetaxel, fever (18 [12%] and 19 [15%]), and neutropenia (22 [14%] and ten [8%]). 154 (60%) of 257 patients died in the intention-to-treat population: 74 (57%) of 129 patients in the doxorubicin group and 80 (63%) of 128 in the gemcitabine and docetaxel group. No deaths were related to the treatment, but two deaths were due to a combination of disease progression and treatment. Interpretation Doxorubicin should remain the standard first-line treatment for most patients with advanced soft-tissue sarcoma. These results provide evidence for clinicians to consider with their patients when selecting first-line treatment for locally advanced or metastatic soft-tissue sarcoma. Funding Cancer Research UK, Sarcoma UK, and Clinical Trial Unit Kantonsspital St Gallen.read more
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Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial
Ian Judson,Jaap Verweij,Hans Gelderblom,Jörg T. Hartmann,Jörg T. Hartmann,Patrick Schöffski,Jean-Yves Blay,J. Martijn Kerst,Josef Sufliarsky,Jeremy Whelan,Peter Hohenberger,Anders Krarup-Hansen,Thierry Alcindor,Thierry Alcindor,Sandrine Marreaud,Saskia Litière,Catherine Hermans,Cyril Fisher,Pancras C.W. Hogendoorn,A Paolo dei Tos,Winette T. A. van der Graaf +20 more
TL;DR: This phase 3 randomised controlled trial assessed whether dose intensification of doxorubicin with ifosfamide improves survival of patients with advanced soft-tissue sarcoma compared with doxorbicin alone.
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Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas
Robert G. Maki,J. Kyle Wathen,Shreyaskumar Patel,Dennis A. Priebat,Scott H. Okuno,Brian L. Samuels,Michael P. Fanucchi,David C. Harmon,Scott M. Schuetze,Denise Reinke,Peter F. Thall,Robert S. Benjamin,Laurence H. Baker,Martee L. Hensley +13 more
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