12 Multiple courses of high-dose alkylating therapy with autologous stem cell support

Abstract

Since the introduction of autologous blood progenitor cell transplantation, (APCT) bone marrow suppression is no longer dose-limiting after high-dose therapy. We have developed a high-dose chemotherapy regimen ‘CTC', that includes cyclophosphamide (6g/m²), thiotepa (480mg/m²) and carboplatin (1600mg/m²) administered over four days. This regimen has been shown to be well-tolerated in over 80 (first) courses and multiple courses could be feasible. 28 patients received 2 courses of CTC, CTC-2 beginning on day 28 after the first APCT. One patient died of sepsis, one developed reversible veno-occlusive disease (VOD). Eleven patients received 3 subsequent courses of CTC. There were three toxic deaths: 1 × sepsis, 1 × VOD, 1 × hemolytic uremic syndrome (HUS). Two other patients developed reversible VOD, one had reversible HUS. While two closely spaced CTC courses are feasible, three subsequent courses are associated with frequent unacceptable organ toxicity. Preliminary data of a phase I/II study in advanced breast cancer suggest that three tightly spaced ‘tiny CTC' courses—containing 2/3 of the doses of each of the agents in a standard CTC course—may be well tolerated and are not associated with excess organ toxicity.