Non-haematological toxicity limiting the application of sequential high dose chemotherapy in patients with advanced...

A programme of repeated high dose chemotherapy for advanced breast cancer was developed using (1) cyclophosphamide 4 g/m2 followed by autologous peripheral blood stem cell (PBSC) collection; (2) three cycles of conventional dose chemotherapy; (3) high dose cyclophosphamide, cisplatin, and carmustine with PBSC rescue; and (4) high dose etoposide and melphalan with PBSC rescue. Fifteen eligible patients had advanced poor prognosis breast cancer either at initial diagnosis (one patient) or at relapse (14 patients). During the course of the protocol, there were three treatment related deaths, two patient withdrawals due to debilitating toxicity, five patient withdrawals due to disease progression, and one patient withdrawal due to inadequate collection of PBSC. The remaining four patients did not complete the planned protocol as the programme was terminated because of the unacceptable morbidity and mortality. They were treated with an alternative high dose chemotherapy protocol which was well tolerated. This study highlights the significant problems associated with a complex sequential high dose chemotherapy regimen. Cyclophosphamide mobilized PBSC infused following high dose chemotherapy enables rapid haematological recovery. However the non-haematological toxicity following high dose chemotherapy regimens is often severe and may limit the application of certain sequential high dose chemotherapy combinations in patients with breast cancer.