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GeDDiS: A prospective randomised controlled phase III trial of gemcitabine and docetaxel compared with doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft tissue sarcomas (EudraCT 2009-014907-29).
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2015
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Surgical OncologyOncologyMalignant DiseaseCancer ManagementSurgical PathologyEudract 2009-014907-29Dox V GemdocPathologyDox 75Metronomic TherapyFirst-line TreatmentMolecular OncologyStandard First-line TreatmentCancer TreatmentMedicineRadiation OncologyGynecology OncologyCancer Research
10500 Background: Standard first-line treatment of locally advanced/metastatic soft tissue sarcoma (STS) is Dox. GemDoc has activity in STS and is used in relapsed STS after failure of at least one line of chemotherapy. Our aim was to compare GemDoc with Dox as first-line treatment of locally advanced/metastatic STS. Methods: Patients (pts) from 24 UK sites and 1 Swiss site were randomised to receive 6 cycles of Dox 75 mg/m2 intravenously (IV) day 1 every 3 weeks, or Gem 675 mg/m2 IV days 1 and 8 and Doc 75 mg/m2 IV day 8 every 3 weeks (wks). Pts had locally advanced/metastatic STS, Trojani grade 2 or 3, disease progression prior to enrolment, no prior chemotherapy for sarcoma, no prior Dox, WHO performance status 0-2, age ≥ 13 years. Pts were stratified by age ( ≤ 18 or > 18 years) and histological subtype (uterine leiomyosarcoma [uLMS], synovial, pleomorphic, and other). Primary endpoint was progression free survival (PFS) rate (PFR) at 24 wks. Results: From Dec 2010 - Jan 2014, 257 pts were randomised (n = 129 Dox; n = 128 GemDoc). Median follow up was 19 months. 61% of pts were female; median age was 55 years. Baseline characteristics were balanced. Histology was 27% uLMS, 4% synovial, 12% pleomorphic, 56% other. PFR at 24 wks was 46.1% v 46.0%, median PFS was 23 v 24wks, for Dox v GemDoc, but the hazard ratio (HR) was 1.28 (95% CI 0.98-1.67, P = 0.07) in favour of Dox. Median OS was 71 v 63 wks (HR = 1.07; 95% CI 0.77-1.49) for Dox v GemDoc. Although the PFS Kaplan-Meier curves did not violate the proportional hazards assumption (p = 0.53), they initially overlapped, and then separated after 24 wks in favour of Dox. Best response (CR/PR/SD) was 65.9% (Dox) v 58.6% (GemDoc). Mean dose intensity was 94.6% (Dox) v 83.3% (GemDoc). 46% (Dox) v 61% (GemDoc) of pts had at least one dose delay; 1 pt (2%) on Dox v 13 pts (16%) on GemDoc stopped treatment early due to toxicity. Conclusions: Although the PFR at 24 wks was the same for Dox and GemDoc, the HR indicated superiority of Dox. Dox was less toxic and easier to deliver than GemDoc, and should remain standard first-line treatment for locally advanced/metastatic STS. Clinical trial information: ISRCTN07742377.