Abstract
Thirty-four patients with previously treated, advanced, low grade NHL were treated with Fludarabine, a deamination-resistant analogue of adenosine arabinoside, at a dose of 25 mg m-2 intravenously, daily for 5 days (median number of cycles = 3, range 1-10). Complete remission (CR) was achieved in six and partial remission (PR) in a further seven. Overall, responses were seen in 11/23 patients (48%) with follicular lymphoma and in 2/11 (18%) with low grade, diffuse NHL. Fifteen patients with previously treated CLL and one patient with prolymphocytic leukaemia (PLL) were also treated as above (median no. of cycles = 3, range 1-6). A partial response was seen in three of the 11 evaluable patients with CLL and CR was achieved in the patient with PLL. There were four deaths due to infection and 19 further episodes requiring admission to hospital. No other significant toxicity was reported in a total of 164 cycles of Fludarabine. This agent is active in advanced low grade lymphoid malignancy. Further studies are required to assess its role in newly diagnosed patients.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Al-Katib A., Koziner B., Kurland E., Little C., Labriola D., Thaler H., Straus D., Lee B., Clarkson B. Treatment of diffuse poorly differentiated lymphocytic lymphoma. An analysis of prognostic variables. Cancer. 1984 Jun 1;53(11):2404–2412. doi: 10.1002/1097-0142(19840601)53:11<2404::aid-cncr2820531107>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
- Anderson T., DeVita V. T., Jr, Simon R. M., Berard C. W., Canellos G. P., Garvin A. J., Young R. C. Malignant lymphoma. II Prognostic factors and response to treatment of 473 patients at the National Cancer Institute. Cancer. 1982 Dec 15;50(12):2708–2721. doi: 10.1002/1097-0142(19821215)50:12<2708::aid-cncr2820501203>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
- Brittinger G., Bartels H., Common H., Dühmke E., Fülle H. H., Gunzer U., Gyenes T., Heinz R., König E., Meusers P. Clinical and prognostic relevance of the Kiel classification of non-Hodgkin lymphomas results of a prospective multicenter study by the Kiel Lymphoma Study Group. Hematol Oncol. 1984 Jul-Sep;2(3):269–306. doi: 10.1002/hon.2900020306. [DOI] [PubMed] [Google Scholar]
- Carbone P. P., Kaplan H. S., Musshoff K., Smithers D. W., Tubiana M. Report of the Committee on Hodgkin's Disease Staging Classification. Cancer Res. 1971 Nov;31(11):1860–1861. [PubMed] [Google Scholar]
- Dow L. W., Bell D. E., Poulakos L., Fridland A. Differences in metabolism and cytotoxicity between 9-beta-D arabinofuranosyladenine and 9-beta-D-arabinofuranosyl-2-fluoroadenine in human leukemic lymphoblasts. Cancer Res. 1980 May;40(5):1405–1410. [PubMed] [Google Scholar]
- Gallagher C. J., Gregory W. M., Jones A. E., Stansfeld A. G., Richards M. A., Dhaliwal H. S., Malpas J. S., Lister T. A. Follicular lymphoma: prognostic factors for response and survival. J Clin Oncol. 1986 Oct;4(10):1470–1480. doi: 10.1200/JCO.1986.4.10.1470. [DOI] [PubMed] [Google Scholar]
- Heinz R., Stacher A., Pralle H., Theml H., Brunswicker F., Burkert M., Common H., Fülle H. H., Grisar T., Grüneisen A. Lymphoplasmacytic/lymphoplasmacytoid lymphoma: a clinical entity distinct from chronic lymphocytic leukaemia? Blut. 1981 Sep;43(3):183–192. doi: 10.1007/BF00363888. [DOI] [PubMed] [Google Scholar]
- Hochster H., Cassileth P. Fludarabine phosphate therapy of non-Hodgkin's lymphoma. Semin Oncol. 1990 Oct;17(5 Suppl 8):63–65. [PubMed] [Google Scholar]
- Huguley C. M., Jr Treatment of chronic lymphocytic leukemia. Cancer Treat Rev. 1977 Dec;4(4):261–273. doi: 10.1016/s0305-7372(77)80002-9. [DOI] [PubMed] [Google Scholar]
- Hutton J. J., Von Hoff D. D., Kuhn J., Phillips J., Hersh M., Clark G. Phase I clinical investigation of 9-beta-D-arabinofuranosyl-2-fluoroadenine 5'-monophosphate (NSC 312887), a new purine antimetabolite. Cancer Res. 1984 Sep;44(9):4183–4186. [PubMed] [Google Scholar]
- ISRAELS L. G., GALTON D. A., TILL M., WILTSHAW E. Clinical evaluation of CB 1348 in malignant lymphoma and related diseases. Ann N Y Acad Sci. 1958 Apr 24;68(3):915–925. doi: 10.1111/j.1749-6632.1958.tb42649.x. [DOI] [PubMed] [Google Scholar]
- Jones S. E., Fuks Z., Bull M., Kadin M. E., Dorfman R. F., Kaplan H. S., Rosenberg S. A., Kim H. Non-Hodgkin's lymphomas. IV. Clinicopathologic correlation in 405 cases. Cancer. 1973 Apr;31(4):806–823. doi: 10.1002/1097-0142(197304)31:4<806::aid-cncr2820310408>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
- Kempin S., Lee B. J., 3rd, Thaler H. T., Koziner B., Hecht S., Gee T., Arlin Z., Little C., Straus D., Reich L. Combination chemotherapy of advanced chronic lymphocytic leukemia: the M-2 protocol (vincristine, BCNU, cyclophosphamide, melphalan, and prednisone). Blood. 1982 Nov;60(5):1110–1121. [PubMed] [Google Scholar]
- Knospe W. H., Loeb V., Jr, Huguley C. M., Jr Proceedings: Bi-weekly chlorambucil treatment of chronic lymphocytic leukemia. Cancer. 1974 Feb;33(2):555–562. doi: 10.1002/1097-0142(197402)33:2<555::aid-cncr2820330234>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
- Leiby J. M., Snider K. M., Kraut E. H., Metz E. N., Malspeis L., Grever M. R. Phase II trial of 9-beta-D-arabinofuranosyl-2-fluoroadenine 5'-monophosphate in non-Hodgkin's lymphoma: prospective comparison of response with deoxycytidine kinase activity. Cancer Res. 1987 May 15;47(10):2719–2722. [PubMed] [Google Scholar]
- Meusers P., Engelhard M., Bartels H., Binder T., Fülle H. H., Görg K., Gunzer U., Havemann K., Kayser W., König E. Multicentre randomized therapeutic trial for advanced centrocytic lymphoma: anthracycline does not improve the prognosis. Hematol Oncol. 1989 Sep-Oct;7(5):365–380. doi: 10.1002/hon.2900070505. [DOI] [PubMed] [Google Scholar]
- Montserrat E., Alcalá A., Parody R., Domingo A., García-Conde J., Bueno J., Ferrán C., Sanz M. A., Giralt M., Rubio D. Treatment of chronic lymphocytic leukemia in advanced stages. A randomized trial comparing chlorambucil plus prednisone versus cyclophosphamide, vincristine, and prednisone. Cancer. 1985 Nov 15;56(10):2369–2375. doi: 10.1002/1097-0142(19851115)56:10<2369::aid-cncr2820561004>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
- Oken M. M., Kaplan M. E. Combination chemotherapy with cyclophosphamide, vincristine, and prednisone in the treatment of refractory chronic lymphocytic leukemia. Cancer Treat Rep. 1979 Mar;63(3):441–447. [PubMed] [Google Scholar]
- Plunkett W., Chubb S., Alexander L., Montgomery J. A. Comparison of the toxicity and metabolism of 9-beta-D-arabinofuranosyl-2-fluoroadenine and 9-beta-D-arabinofuranosyladenine in human lymphoblastoid cells. Cancer Res. 1980 Jul;40(7):2349–2355. [PubMed] [Google Scholar]
- Rai K. R., Sawitsky A., Cronkite E. P., Chanana A. D., Levy R. N., Pasternack B. S. Clinical staging of chronic lymphocytic leukemia. Blood. 1975 Aug;46(2):219–234. [PubMed] [Google Scholar]
- Rohatiner A. Z., Price C. G., Arnott S., Norton A., Evans M. L., Cotter F., Dorey E., Davis C. L., Clark P., Sterlini J. Myeloablative therapy with autologous bone marrow transplantation as consolidation of remission in patients with follicular lymphoma. Ann Oncol. 1991 Feb;2 (Suppl 2):147–150. doi: 10.1007/978-1-4899-7305-4_23. [DOI] [PubMed] [Google Scholar]
- Sawitsky A., Rai K. R., Glidewell O., Silver R. T. Comparison of daily versus intermittent chlorambucil and prednisone therapy in the treatment of patients with chronic lymphocytic leukemia. Blood. 1977 Dec;50(6):1049–1059. [PubMed] [Google Scholar]
- Smith O. P., Mehta A. B. Fludarabine monophosphate for prolymphocytic leukaemia. Lancet. 1990 Sep 29;336(8718):820–820. doi: 10.1016/0140-6736(90)93293-x. [DOI] [PubMed] [Google Scholar]
- Spriggs D. R., Stopa E., Mayer R. J., Schoene W., Kufe D. W. Fludarabine phosphate (NSC 312878) infusions for the treatment of acute leukemia: phase I and neuropathological study. Cancer Res. 1986 Nov;46(11):5953–5958. [PubMed] [Google Scholar]
- Swerdlow S. H., Habeshaw J. A., Murray L. J., Dhaliwal H. S., Lister T. A., Stansfeld A. G. Centrocytic lymphoma: a distinct clinicopathologic and immunologic entity. A multiparameter study of 18 cases at diagnosis and relapse. Am J Pathol. 1983 Nov;113(2):181–197. [PMC free article] [PubMed] [Google Scholar]