Fludarabine (Fludara) and 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.