Fludarabine Phosphate

PURPOSE: Fludarabine phosphate (F-AMP), a purine analog, requires daily intravenous administration. A pharmacokinetic study of an oral formulation (10 mg immediate-release tablet) was undertaken in patients with “low-grade” non-Hodgkin's lymphoma and B-cell chronic lymphocytic leukemia. PATIENTS AND METHODS: Oral F-AMP was incorporated into the “conventional” treatment schedule. Single oral trial doses of 50, 70, and 90 mg of F-AMP were given on the first day of three cycles of treatment; a comparative 50-mg intravenous trial dose was given on the first day of the fourth cycle. Intravenous F-AMP (25 mg/m2) was given on days 2 to 5 at 4-week intervals. Pharmacokinetic samples taken after each trial dose were analyzed for plasma 2-fluoro-arabinofuranosyl-adenine (2F-ara-A) concentration (its main metabolite); area under the curve 0 to 24 hours (AUC(0-24h)) and maximum concentration (Cmax) were calculated. Eighteen patients received all three oral trial doses, and bioavailability was determined in 15 patients who completed four courses of therapy. RESULTS: Oral administration of F-AMP resulted in a dose-dependent increase in Cmax and AUC(0-24h) of 2F-ara-A and achieved an AUC(0-24h) similar to intravenous administration, although at a lower Cmax. The linear increase in mean AUC(0-24h) by factors of 1.36 ± 0.22 (mean ± SD) and 1.72 ± 0.31 corresponded well with the increase in oral dose from 50 to 70 mg (factor of 1.4) and 90 mg (factor of 1.8), respectively. Bioavailability (approximately 55%, with low intraindividual variation) and time to Cmax were dose independent. CONCLUSION: Oral doses of F-AMP can achieve an AUC(0-24h) of 2F-ara-A similar to intravenous administration, with dose-independent bioavailability. The tablet will greatly enhance the use of F-AMP in a palliative setting.

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Fludarabine Phosphate as an Active and Well Tolerated Salvage Therapy in an Elderly Heavily Pretreated Hodgkin's Disease Patient: A Case Report

Tumori Journal ◽

10.1177/030089169908500415 ◽

1999 ◽

Vol 85 (4) ◽

pp. 288-289 ◽

Cited By ~ 2

Author(s):

Roberto Bordonaro ◽

Francesco Ferraù ◽

Dario Giuffrida ◽

Stefania Cali ◽

Domenico Priolo ◽

...

Keyword(s):

Case Report ◽

Salvage Therapy ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Disease Patient ◽

Fludarabine Phosphate ◽

Heavily Pretreated

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Phase II trial of fludarabine phosphate in lymphoma: an effective new agent in low-grade lymphoma.

Journal of Clinical Oncology ◽

10.1200/jco.1992.10.5.790 ◽

1992 ◽

Vol 10 (5) ◽

pp. 790-794 ◽

Cited By ~ 155

Author(s):

J R Redman ◽

F Cabanillas ◽

W S Velasquez ◽

P McLaughlin ◽

F B Hagemeister ◽

...

Keyword(s):

Phase Ii ◽

Phase Ii Trial ◽

Cell Lymphoma ◽

Large Cell ◽

Complete Response ◽

Low Grade ◽

High Grade ◽

Major Activity ◽

Fludarabine Phosphate ◽

Large Cell Lymphoma

PURPOSE In a phase II trial we investigated fludarabine phosphate (FAMP) as therapy for patients with relapsed lymphoma to determine its effectiveness and toxicity in this disease. PATIENTS AND METHODS The 67 assessable patients had a median age of 56 years and had received a median of three chemotherapy regimens before treatment with FAMP. The starting dose was 25 mg/m2 administered intravenously over 30 minutes daily for 5 days every 3 to 4 weeks. RESULTS High response rates were observed for follicular small cleaved-cell lymphoma (FSCCL) (62%), follicular mixed small- and large-cell lymphoma (80%), and follicular large-cell lymphoma (FLCL) (100%). Responses also occurred in small lymphocytic lymphoma (SLL) (33%), transformed lymphoma (33%), mycosis fungoides (40%), and Hodgkin's disease (25%). No responses were observed in other intermediate- or high-grade lymphomas (N = 20). Overall, there were five patients with a complete response, 23 patients with a partial response, and an overall response rate of 37%. Toxicity was primarily hematologic and infectious. No significant gastrointestinal, hepatic, renal, or neurologic toxicity occurred. CONCLUSIONS We conclude that FAMP has major activity in follicular lymphoma. Fundamental research is needed to understand this differential efficacy in low-grade lymphoma yet lack of efficacy in intermediate- and high-grade lymphoma. Clinical investigations should be done using FAMP in varying dose schedules and in combination regimens.

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Evaluation of fludarabine phosphate in small cell carcinoma

Investigational New Drugs ◽

10.1007/bf00170779 ◽

1988 ◽

Vol 6 (1) ◽

Cited By ~ 4

Author(s):

JohnM. Rainey ◽

JulianB. Hill ◽

John Crowley

Keyword(s):

Cell Carcinoma ◽

Small Cell Carcinoma ◽

Small Cell ◽

Fludarabine Phosphate

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Analisi di minimizzazione dei costi del trattamento della leucemia cronica con fludarabina fosfato (Fludara®) e.v. e p.o.: metodologia e risultati di un’indagine empirica

Farmeconomia Health economics and therapeutic pathways ◽

10.7175/fe.v5i4.810 ◽

2004 ◽

Vol 5 (4) ◽

pp. 265-272

Author(s):

Carlo Lazzaro

Keyword(s):

Hospital Stay ◽

Drug Administration ◽

Drug Acquisition ◽

Oral Formulation ◽

Drug Preparation ◽

Day Hospital ◽

Hospital Perspective ◽

Fludarabine Phosphate ◽

Before And After ◽

Outpatient Drug

The aim of the paper is to compare healthcare-related costs of a 5-day course with fludarabine phosphate i.v. vs a 5-day course with oral fludarabine phosphate in Italian patients with chronic leukemia. A cost-minimization analysis was performed from both Italian National Healthcare Service (INHS) and hospital perspectives. Healthcare-related costs were collected from 2 out of a sample of 28 Ematology wards and included those of drug acquisition, drug preparation, drug administration, reception and discharge of patient before and after drug administration; hospital overheads were calculated as a percentage of the total healthcare-related costs. The reimbursement schemes for acquisition and administration of fludarabine phosphate i.v. were gathered from the whole sample of 28 Ematology wards taken into account. Costs were expressed in euros 2004. When compared to fludarabine phosphate i.v., oral fludarabine phosphate allowed savings ranging from 223,47 euros (hospital perspective) to 477,05 euros (INHS perspective) per patient. As far as hospital perspective was concerned, savings associated with oral fludarabine phosphate were due to hospital overheads (115.1%), drug preparation (19.6%), drug administration (17.3%), reception and discharge of patient before and after drug administration (2.9%), whereas costs for drug acquisition was higher for oral formulation (-54.8%). When INHS perspective was taken into account, 3 out of 28 Ematology wards (11%) were reimbursed on a drug-plus-outpatient-drug-administration-basis, whereas 25 out of 28 Ematology wards (89%) were reimbursed on a day-hospital-stay-basis. Savings associated with oral fludarabine phosphate were due to day-hospital stay (253.4%), outpatient drug administration (1.1%), whereas cost for drug acquisition were higher for oral formulation (-154.5%). Sensitivity analysis confirmed the robustness of basecase results. Savings associated with oral fludarabine phosphate may be of relevant interest for INHS policies aimed at reducing public expenditure for drugs in Italy.

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Follow-Up Results of a Prospective, Multicenter, Open-Label Study of Oral Fludarabine Phosphate in Patients with Previously Untreated B-CLL.

Blood ◽

10.1182/blood.v106.11.2128.2128 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2128-2128

Author(s):

Jean-Francois Rossi ◽

A. Van Hoof ◽

K. De Boeck ◽

S. A. Johnson ◽

D. Bron ◽

...

Keyword(s):

Disease Progression ◽

Median Time ◽

Response Rate ◽

Time To Progression ◽

Open Label ◽

Overall Response ◽

Fludarabine Phosphate ◽

Duration Of Response ◽

Grade 3

Abstract The IV formulation of fludarabine phosphate is an effective treatment in patients with B-cell chronic lymphocytic leukemia (B-CLL), yielding overall response rates of 60% to 80%. An oral formulation of fludarabine phosphate has been developed. In a previously published multicenter, open-label, phase II clinical trial, 81 previously untreated B-CLL patients received 10-mg tablets of fludarabine phosphate (Fludara® oral) 40 mg/m2/day for 5 days, repeated every 4 weeks. The primary endpoint of the trial was response rate, and secondary endpoints included safety and quality of life assessments. Of 81 patients (mean age, 61.2 years; range, 30–75 years) with previously untreated B-CLL, 81.5% were classified as Binet stage B or C. The overall response rate (complete response [CR] + partial response [PR]) using National Cancer Institute (NCI) criteria was 80.2% (12.3% CR and 67.9% PR) and the median time to progression was 841 days (range, 28–1,146 days) (Rossi JF, et al. J Clin Oncol2004;22:1260–1267). The most frequently reported grade 3/4 adverse event was myelosuppression: WHO grade 3/4 hematologic toxicities included granulocytopenia (32.1%), anemia (9.9%), and thrombocytopenia (4.9%). This analysis reports on the long-term follow-up of this cohort during the period from November 2001 to November 2004. Of the 74 patients eligible for the survival analysis, 61 were also assessed for duration of response using NCI criteria: 9 CR (14.8%) and 52 PR (82.2%). During the 3-year follow-up period, 22 (29.7%) patients did not progress. For those who progressed, median time to progression was 29.7 months, and median duration of response was 22.9 months. In 41 (80.4%) of these patients, an increase in circulating lymphocytes was reported as evidence of disease progression. In 23 patients (45.1%), an increase in the sum of the products of at least 2 lymph nodes and/or appearance of new palpable nodes was reported as evidence of disease progression. During the indicated follow-up period, 37 patients (50%) received subsequent treatment. Twelve patients (16.2%) died during the follow-up period: 7 patients (58.3%) due to disease progression, 3 patients (25.0%) due to adverse events, and 2 patients (16.7%) due to other causes. Results from this study suggest that oral fludarabine phosphate is clinically effective and well tolerated by patients with previously untreated B-CLL. Moreover, these data demonstrate that oral fludarabine phosphate achieves response rates and duration of response comparable to those achieved with first-line fludarabine phosphate IV therapy.

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