Fludarabine, cyclophosphamide, and dexamethasone (FluCyD) combination is effective in pretreated low-grade non-Hodgkin's lymphoma

Purpose: Fludarabine phosphate is effective as a single agent in low-grade non-Hodgkin's lymphoma (NHL). Combined with other antineoplastic agents it enhances the antitumor effect. Our aim was to define the therapeutic effica cy and toxicity of a combination of fludarabine, cyclophosphamide and dexam ethasone (FluCyD) in patients with advanced low-grade lymphoma. Patients and methods: Twenty-five adults with pretreated advanced-stage low -grade NHL were treated with three-day courses of fludarabine 25 mg/m(2)/da y, cyclophosphamide 350 mg/m(2)/day, and dexamethasone 20 mg/day, every fou r weeks for a maximum of six courses. Results. Of the 25 patients, 18 (72%) responded, 8 (32%) achieving CR and 1 0 (40%) PR. Seven were failures. The median follow-up was 21 months (5-26). Eight CR patients remain in CR after 5-21 months. Of 10 PR patients, 3 are in continuous PR without further treatment after 12, 17 and 18 months. Mye losuppression was the most prevalent toxic effect. Although severe granuloc ytopenia (granulocyte count nadir <500/mu l) and thrombocytopenia (platelet count nadir < 50.000/mu l) occurred in only 10% and 16% of courses, respec tively, slow granulocyte or platelet count recovery caused delay of 40% of the courses. Nine patients (36%) required discontinuation of therapy becaus e of persistent granulocytopenia and/or thrombocytopenia: three after one c ourse, three after 2-4 courses, and three after five courses. Thirteen infe ctious episodes in 11 patients complicated 11% of courses. Two of 10 patien ts monitored for the circulating EBV load showed increased viral load. One of these developed aggressive lymphoma. CD4+ lymphocytes declined from a pr e-therapy median value of 425/mu l to 141/mu l post-treatment (P = 0.001). Non-hematologic toxicities were rare and mild. Conclusions. The combination of fludarabine with cyclophosphamide and dexam ethasone is effective in pretreated advanced-stage low-grade NHL. It may br oaden the range of therapeutic options in the salvage treatment of these pa tients. The main toxicity of this combination is prolonged myelosuppression that may cause treatment delay or withdrawal. The benefit of adding granul ocyte colony-stimulating factor, particularly in patients with poor marrow reserve, needs to be investigated.