DOUBLE DOSE-INTENSIVE CHEMOTHERAPY WITH AUTOLOGOUS STEM-CELL SUPPORT FOR METASTATIC BREAST-CANCER - NO IMPROVEMENT IN PROGRESSION-FREE SURVIVAL BY THE SEQUENCE OF HIGH-DOSE MELPHALAN FOLLOWED BY CYCLOPHOSPHAMIDE, THIOTEPA, AND CARBOPLATIN

Purpose: Twenty-one percent of responding metastatic breast cancer pat ients remain progression-free a median 50 months following one intensi fication cycle of cyclophosphamide (6,000 mg/m(2)), thiotepa (500 mg/m (2)), and carboplatin (800 mg/m(2)) (CTCb) with autologous bone marrow transplantation (ABMT). This trial studied whether the sequence of hi gh-dose melphalan followed by CTCb resulted in improved disease respon se and duration. Methods: Women with at least partial responses (PRs) to induction received melphalan (140 or 180 mg/m(2)) with peripheral-b lood progenitor cell (PBPC) and granulocyte colony-stimulating factor (G-CSF) support. They were monitored as outpatients. After recovery, p atients were hospitalized for CTCb with marrow, PBPC, and G-CSF suppor t. Results: Data on 67 women, at a median of 25 months from CTCb, were examined. After melphalan, 49 (73%) required admission for fever (89% ), mucositis (35%), or infection (15%) (median stay, 8 days). All rece ived CTCb. For the first 33 patients, the median days from start of me lphalan to CTCb was 24. After liver toxicity (one death from venoocclu sive disease [VOD]) developed in 11 patients during CTCb, the interval between intensifications was increased to 35 days without incident. T wenty-three patients (34%) are progression-free a median of 16 months post-CTCb. The median progression-free survival (PFS) and survival rim es for the whole group are estimated at 11 and 20 months, respectively . Conclusion: Treatment with this sequence of high-dose melphalan foll owed by CTCb has not resulted in superior PFS to date, when compared w ith single-intensification CTCb. This report discusses factors related to patient selection, the role of induced drug resistance, and the sc hedule of administration of alkylating agents that may adversely influ ence outcome. (C) 1996 by American Society of Clinical Oncology.