PHASE I-II TRIAL OF HIGH-DOSE CYCLOPHOSPHAMIDE, CARBOPLATIN AND AUTOLOGOUS BONE-MARROW OR PERIPHERAL-BLOOD STEM-CELL RESCUE

In an effort to evaluate the toxicities and anti-tumor efficacy of the combination of high-dose cyclophosphamide (CY) and carboplatin, we un dertook a phase I-II trial with autologous bone marrow (BM) or periphe ral blood stem cell (PBSC) rescue for patients with solid tumors, Fort y three patients, 39 of whom had either high risk stage II or III or m etastatic breast cancer were treated with escalating doses of carbopla tin 1200-1800 mg/m(2) and cyclophosphamide 4800-6000 mg/m(2) over 3 da ys followed by autologous BM or PBSC infusion, No life-threatening or fatal toxicities were observed, Reversible congestive heart failure wa s seen in two patients, Transient hepatotoxicity, characterized primar ily by elevation of transaminase levels, and nausea and vomiting, adeq uately managed with anti-emetic therapy, were seen in 39 and 40 of 43 patients, respectively, The 14 month post-transplant probability of re lapse-free survival for 26 patients with high risk II-III breast cance r was 79%; for 13 patients with metastatic disease, the 22 month relap se-free survival probability was 23%. High-dose carboplatin and CY at maximally administered doses of 1800mg/m2 and 6000 mg/m(2) is a well t olerated preparative transplant regimen for autologous BM or PBSC tran splantation. It appears to have similar anti-tumor activity and an imp roved safety profile when compared with other commonly employed transp lant preparative regimens.