2002 CTOS Annual Meeting Oral Presentations — Medical Oncology

RANDOMISED PHASE 3 TRIAL OF TWO INVESTIGATIONAL SCHEDULES OF IFOSFAMIDE VERSUS STANDARD DOSE DOXORUBICIN IN PATIENTS WITH ADVANCED OR METASTATIC SOFT TISSUE SARCOMA (ASTS)
[Abstract ID: 20]

Category: Medical Oncology

Presentation: Oral

Authors: Paul Lorigan¹, Jaap Verweij¹, Z Papai¹, S Rodenhuis¹, A Le Cesne¹, M Leahy¹, John Radford¹, Pancras Hogendoorn¹, Anne Kirkpatrick¹, Ole S Nielson¹

Author Institutions: ¹EORTC Soft Tissue and Bone Sarcoma Group, Brussels, Belgium

Presenter: Paul Lorigan
paul.lorigan@christie-tr.nwest.nhs.uk

Correspondent: Paul Lorigan
paul.lorigan@christie-tr.nwest.nhs.uk
Manchester United Kingdom M20 4BX
Ph: 0161 446 3000
Fax: 0161 446 3299

Objectives: Doxorubicin and ifosfamide show significant activity in soft tissue sarcoma but have never been formally compared. We report a randomised Phase III comparison of single agent doxorubicin 75mg/m2 versus ifosfamide 3g/m2 over 4 hours daily for 3 days (Ifos 3*3) versus ifosfamide 9g/m2 over 72 hours by continuous infusion (Ifos 9) in patients with ASTS.

Methods: Patients were stratified by histological subtype, grade, metastatic site, performance status and institution. Response was evaluated after each 2 cycles and all responses independently reviewed. An interim analysis was carried out by an independent data monitoring committee after four years.

Results: Between 1997 and Sept 2001, 322/760 patients were recruited. Groups were evenly divided by stratification factors. Histological types were leiomyosarcoma 31.4%, liposarcoma 12.1%, synovial sarcoma 9.3%, others 46.2%. Toxicity was worse in both ifosfamide arms; grade 3 febrile neutropenia occurred in 8.3% doxorubicin patients, 20.7% Ifos 3*3 and 17% Ifos 9 patients. Response rates were: Doxorubicin 11% (CR 0.9%, PR 10.1%), Ifos 3*3 6.5% (CR 0.9%, PR 5.6%), Ifos 9 9.4% (CR 1.9%, PR 7.5%). With a median follow up of 14 months, there was no significant difference in progression free or overall survival in the three arms. The study hypothesis of a difference of 10% in PFS at 1 year was rejected and the trial stopped early on the advice of an independent data monitoring committee.

Conclusions: For the majority of patients with ASTS for whom single agent chemotherapy is appropriate, doxorubicin 75mg/m2 remains the treatment of choice.