Fludarabine (Fludara) and cyclophosphamide(Drug information on cyclophosphamide) (Cytoxan, Neosar) are two highly active agents in the treatment of indolent lymphomas. In vitro, these agents are synergistic. Preliminary reports of clinical trials indicate increased complete response rates over the single agents. However, concern remains about the toxic effects of the agents when used in combination, especially the incidence of opportunistic infections, and also about the best dose and schedule.
We have completed accrual to a phase II trial of fludarabine and cyclophosphamide in patients with previously untreated indolent lymphoproliferative disorders. Eligibility includes age ³ 18 years, low-grade and select intermediate-grade lymphoproliferative disorders, symptomatic disease, and good organ function.
Patients received cyclophosphamide (600 mg/m² IVon day 1) and fludarabine (20 mg/m² IV on days 1-5). Chemotherapy was repeated every 28 days. Bone marrow transplant (BMT) candidates received only four cycles. Other patients received a maximum of six cycles. Patients received Pneumocystis carinii (PCP) prophylaxis and support withgranulocyte colony-stimulating factor (filgrastim [Neupogen]).
A total of 39 patients were entered into the study (28 male/11 female; median age, 53 years [range 30-73 years]). Thirty-eight patients are evaluable for response
.One patient died of unknown cause shortly after receiving the second cycle of chemotherapy. One patient was diagnosed with cryptococcal pneumonia during the second cycle of chemotherapy. One patient developed focal seizures 30 days after the fourth cycle of chemotherapy that have not recurred and are of uncertain etiology. One patient developed grade 4 pulmonary toxicity. Hematopoietic toxicity was mild. Nausea, vomiting, and alopecia were minimal.
CONCLUSIONS: We conclude that this is a highly active and well-tolerated regimen. Careful attention must be given to prophylaxis against opportunistic infections.