Fludarabine: a new agent with marked cytoreductive activity in untreated chronic lymphocytic leukemia.

Abstract

Thirty-three patients with chronic lymphocytic leukemia (CLL) with advanced Rai stage (III-IV) or progressive Rai stage (0-II) disease were treated with fludarabine as a single agent. Eleven patients (33%) obtained a complete remission (CR), 13 (39%) a clinical CR with residual nodules as the only evidence of disease (nodular partial remission [PR]), and two patients (6%) achieved a PR for a total response rate of 79%. Response was rapid, usually occurring after three to six courses of treatment. The major morbidity was infection. Febrile episodes occurred in 13% of the courses (pneumonia 6%, minor infection 4%, and transient fever of undocumented cause 3%). Fludarabine appears to be the most cytoreductive single agent so far studied in CLL.

Fludarabine phosphate for the treatment of low grade lymphoid malignancy

“…Despite this unfavourable setting, undoubted activity has been demonstrated in both CLL and follicular NHL, in accordance with other results (Grever et al, 1986;Leiby et al, 1987;Redman et al, 1988;Keating et al, 1989a;Hochster & Cassileth, 1990;Puccio et al, 1990).…”

“…An active triphosphate metabolite is formed intracellularly which intereferes with DNA synthesis by inhibition of DNA polymerase and ribonucleotide reductase (Huang & Plunkett, 1986 murine models has been borne out in Phase I and II testing (Hutton et al, 1984;Spriggs et al, 1986;Champagne et al, 1987). At a dose of < 125 mg/m2/course, significant activity, with response rates of 60% and more, has been reported in CLL and follicular NHL, with some modest benefit in diffuse low grade lymphoma (Grever et al, 1986;Leiby et al, 1987;Redman et al, 1988' Hochster & Cassileth, 1990Keating et al, 1989a;Puccio et al, 1990). Fludarabine is reported to be well tolerated at such doses, the toxicity in these studies being predominantly infective episodes arising from myelosuppresion.…”

Consolidation therapy with high-dose cyclophosphamide improves the quality of response in patients with chronic lymphocytic leukemia treated with fludarabine as induction therapy

“…Nodular responses are not separately reported and therefore the incidence of CR in these reports may include patients with nodular responses. Our result of CR plus nodular responses in 16% of patients may be consistent with the 21% incidence of CR in the European trial 24 and 27% CRs reported by Rai et al 19 These results contrast with the report by Keating et al, 9 in which 33% of patients achieved a CR to single agent fludarabine. The reported differences in the frequency of CR may be due to several reasons, including patient selection, criteria for response, and fludarabine dose delivered.…”

“…1,2 In general, these responses are not durable and patients ultimately succumb to progressive resistant disease. The introduction of three new agents; fludarabine, 3,4 cladribine 5,6 and pentostatin 7,8 has renewed interest in aggressive therapy of selected patients with CLL. Of these drugs, fludarabine has been the most widely studied.…”

“…The ability of fludarabine to induce complete responses in a minority of previously untreated patients 9,10 led to investigation of combination chemotherapy with corticosteroids 11,12 or chlorambucil. 13,14 In general, results of concomitant therapy with fludarabine combined with a second agent were disappointing with increased toxicity limiting dose intensity and without clear-cut improvement in frequency of response.…”