High-dose tri-alkylator chemotherapy with autologous stem cell rescue in patients with refractory malignancies.

Forty patients with refractory solid tumors or non-Hodgkin's lymphoma were treated with high-dose cyclophosphamide, thiotepa, and carmustine (BCNU), followed by autologous stem cell rescue, in a phase I dose escalation study. The dose-limiting toxic effect was delayed drug-induced pulmonary disease, seen in three patients who received 660-750 mg of BCNU/m2 in combination with cyclophosphamide and thiotepa. The early death rate due to toxic effects was 20%; all deaths were attributed to sepsis or respiratory failure. The overall response rate was 63%. The median time to disease progression was 14 weeks. Although this regimen provided effective cytoreduction, its use in heavily pretreated patients with bulky disease is of limited value.