Induction, mobilization of peripheral blood stem cells (PBSC), high-dose chemotherapy and PBSC infusion in patients with untreated stage IV breast cancer: outcomes by intent to treat analyses

Autor: Raefsky E, Kalman L, R Leff, WH West, FA Greco, B McAneny, Buckner Cd, C H Weaver, M Magee, J Hainsworth, T. Alberico, Lee S. Schwartzberg, R Birch
Rok vydání: 1997
Předmět:
Zdroj: Bone Marrow Transplantation. 19:661-670
ISSN: 1476-5365
0268-3369
DOI: 10.1038/sj.bmt.1700728
Popis: Summary: complete remission (CR) rates (40‐50%) with median overall survivals of 18‐24 months and progression-free survivals (PFS) of 12‐25% in patients with breast cancer We investigated the outcomes of patients with breast cancer undergoing induction chemotherapy, mobiliz- responsive to conventional induction chemotherapy. 1‐6 A recent randomized phase III trial demonstrated the superioration of peripheral blood stem cells (PBSC) and highdose chemotherapy (HDC) with PBSC infusion. One ity of two cycles of HDC with peripheral blood stem cell (PBSC) support compared to conventional-dose treatment hundred and fourteen patients with untreated stage IV breast cancer, with a median age of 46 years (range 24‐ in patients with newly diagnosed metastatic breast cancer. 7 Although HDC with PBSC support may be superior to 62), were entered on a phase II trial consisting of: (1) doxorubicin, 5-flurouracil, methotrexate (AFM) × 4 conventional-dose chemotherapy, the majority of patients will relapse and die of progressive disease or of attempts courses at 2 week intervals; (2) cyclophosphamide (4 g/m 2 ), etoposide (600 mg/m 2 ), cisplatin (105 mg/m 2 ) at salvage treatment. 5 In order to design future clinical trials it is important to determine the characteristics of patients (CEP), filgrastim (6mg/kg/day) and PBSC collection; (3) cyclophosphamide (6 g/m 2 ), thiotepa (500 mg/m 2 ), car- who are not likely to benefit from current HDC regimens and to determine the applicability of HDC to the general boplatin (800 mg/m 2 ) (CTCb) followed by PBSC infusion. All patients received AFM, 107 (94%) received population of patients presenting with newly diagnosed metastatic breast cancer. CEP, 93 (82%) received CTCb and PBSC as per protocol and 99 (87%) ultimately received HDC and PBSC. A phase II study was designed to enroll patients with stage IV breast cancer at diagnosis and to evaluate outThere was one infectious death after AFM and all other deaths were associated with progressive disease. Fifty- comes following the sequential administration of induction chemotherapy, chemotherapy and growth factor mobiliztwo patients (46%) are alive, 21 (18%) without progression, at a median 31 months (range 22‐47). The ation of PBSC and HDC followed by PBSC infusion. Outcomes were analyzed and reported on an intent to treat basis probabilities of survival and progression-free survival at 3.5 years were 0.40 and 0.17, respectively. All 62 with a minimum follow-up of 24 months from enrollment. patients with visceral disease and/or a prior history of doxorubicin adjuvant therapy have relapsed or pro- Patients and methods gressed. We conclude that the sequential administration of AFM, CEP and CTCb followed by PBSC resulted in Between March 1992 and January 1994, 120 patients with untreated stage IV breast cancer were enrolled in a phase long-term PFS only in patients who were NED, had bone-only disease or had lymph node or soft tissue dis- II trial of chemotherapy induction, chemotherapy and filgrastim mobilization of PBSC, HDC and infusion of PBSC. ease with or without bone disease. Other strategies, aimed at improving responses to initial therapy, Patients were eligible if they had newly diagnosed and untreated breast cancer (except for adjuvant therapy), were improving HDC regimens and/or developing immunomodulatory therapies, will be necessary to improve PFS 65 years of age or less, had an ECOG performance of 0‐ 1 and evidence of adequate hepatic, renal and cardiac funcfor patients who fail doxorubicin adjuvant or who have visceral disease. tion. Pre-menopausal women could be entered on the study without a previous trial of hormonal therapy. All patients
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