INDUCTION, MOBILIZATION OF PERIPHERAL-BLOOD STEM-CELLS (PBSC), HIGH-DOSE CHEMOTHERAPY AND PBSC INFUSION IN PATIENTS WITH UNTREATED STAGE-IVBREAST-CANCER - OUTCOMES BY INTENT TO TREAT ANALYSES

We investigated the outcomes of patients with breast cancer undergoing induction chemotherapy, mobilization of peripheral blood stem cells ( PBSC) and high-dose chemotherapy (HDC) with PBSC infusion. One hundred and fourteen patients with untreated stage IV breast cancer, with a m edian age of 46 years (range 24-62), mere entered on a phase II trial consisting of: (1) doxorubicin, 5-flurouracil, methotrexate (AFM) x4 c ourses at 2 week intervals; (2) cyclophosphamide (4 g/m(2)), etoposide (600 mg/m(2)), cisplatin (105 mg/m(2)) (CEP), filgrastim (6 mu g/kg/d ay) and PBSC collection; (3) cyclophosphamide (6 g/m(2)), thiotepa (50 0 mg/m(2)), carboplatin (800 mg/m(2)) (CTCb) followed by PBSC infusion . All patients received AFM 107 (94%) received CEP, 93 (82%) received CTCb and PBSC as per protocol and 99 (87%) ultimately received HDC and PBSC. There was one infectious death after AFM and all other deaths w ere associated with progressive disease. Fifty-two patients (36%) are alive, 21 (18%) without progression, at a median 31 months (range 22-4 7). The probabilities of survival and progression-free survival at 3.5 rears were 0.40 and 0.17, respectively. All 62 patients with visceral disease and/or a prior history of doxorubicin adjuvant therapy have r elapsed or progressed. We conclude that the sequential administration of BFM, CEP and CTCb followed by PBSC resulted in long-term PFS only i n patients who mere NED, had bone-only disease or had lymph node or so ft tissue disease with or without bone disease. Other strategies, aime d at improving responses to initial therapy, improving HDC regimens an d/or developing immunomodulatory therapies, will be necessary to impro ve PFS for patients who fail doxorubicin adjuvant or who have visceral disease.