High-dose chemotherapy (HD-CT) with haematopoietic stem cells transplantation (HSCT) for metastatic breast cancer (MBC): the French PEGASE 04 protocol.

JP Lotz, M.D., 123, H Curé, M.D. 23, M Janvier, M.D. 23, F Morvan, M.D. 23, M Legros, M.D.23, B Audhuy, M.D. 23, P Biron, M.D. 23, B Asselain, M.D. 23, M. Guillemot, Ph.D. 2, C Cailliot, M.D. 4, C Le Maignan, M.D.1, T Delozier, M.D. 2, S Glaisner, M.D. 2, D Maraninchi, M.D. 23, H Roché, M.D. 23, C Gisselbrecht, M.D

1 Tenon and Saint-Louis Hospitals, Assistance Publique - Hôpitaux de Paris ; 2 The PEGASE Group French Federation of Anti-Cancer Centers ; 3 The French Society of Bone Marrow Transplantation and Cellular Therapy, 4 Laboratoires Amgen, Paris, France.

Rationale : Based on the relationship between dose intensity and response of MBC, a number of phase II HD-CT studies have been published. It was concluded that HD-CT should only be proposed for chemosensitive diseases but has yet to be evaluated in randomised studies. Gisselbrecht et al have published in 1996 a phase II trial in which 61 patients (pts) were proposed for HD-CT using the CMA regimen [Mitoxantrone : 60 mg/m², Cyclophosphamide : 120 mg/kg, Melphalan : 140 mg/m²]. HD-CT resulted in a median OS time of 33 months and a median EFS time of 20 months from the start of therapy. These results laid the ground work for further evaluation in randomised trials. Purpose: The aim of the PEGASE 04 protocol was to evaluate the impact on PFS of HD-CT over conventional CT for MBC. To detect a difference of 25% in the 2-year progression-free rate (from 25% to 50%), 156 pts have been planned to be enrolled in 3 years. Due to a too low rate of enrollment, it was decided to prematurely stop the inclusions in 12/96. Population : Between 09/92 and 12/96, 61 pts (median age, 44 y ; premenopausal, 48, first metastatic relapse, 39 ; metastatic at diagnosis, 22) with chemosensitive MBC (13 in CR, 48 in PR) were randomised between : 1) the CMA regimen (29 pts), and 2) 4 additional courses of CT (32 pts). Population were well-balanced in term of staging and previous therapy. Results : Considering the data presented during the ASCO 1999-2001 meetings, it was decided to submit this study to an external review committee. The results of the PEGASE 04 protocol will be presented during the meeting.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Stem Cell Biology.