High-dose cyclophosphamide in the treatment of refractory lymphomas and solid tumor malignancies

Twenty-two patients with refractory solid tumors or lymphoma were treated with a single course of high-dose cyclophosphamide (120 mg/kg intravenously [IV] over 2 days) whereas three patients received two courses each. Marrow infusion was not used. In the 22 courses evaluable for tumor response there were 14 responses (64%) of which 11 were partial responses (PR) (50%) and three complete responses (CR) (14%). In the 12 evaluable courses given in patients with lymphoid malignancies a partial response was obtained in seven (58%) and complete response in two (17%) for an overall response rate of 75%. The median duration of response was short: 2 months (range, 1-12 months). Twenty-seven courses were evaluable for toxicity. All patients had nadir polymorphonuclear leukocytes counts less than 500/mm3 with median time to recovery to a level greater than 500/mm3 of 9 days (range, 6-21 days). The median nadir platelet count was 30,000/mm3. One patient had prolonged thrombocytopenia of 225 days. There were two toxic deaths related to leukopenia, one secondary to Pneumocystis carinii pneumonia, and the second from probable sepsis and cholecystitis. Nineteen patients had previously received cyclophosphamide in standard doses. In the patients with lymphoid malignancies who had previously received cyclophosphamide, 22% achieved a CR with an overall response rate of 78%. High-dose cyclophosphamide may be given with acceptable toxicity in heavily pretreated patients. Given the short response duration in patients with progressive disease, the optimal results of such high-dose cyclophosphamide may be achieved when it is employed earlier in the natural history of the disease in conjunction with other alkylators, or as consolidation therapy.