|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
© 2003 American Society for Clinical Oncology
Fludarabine Versus Cyclophosphamide, Vincristine, and Prednisone in Recurrent Low-Grade LymphomasHematology/Oncology Division, General Hospital of Annemasse, Annemasse, France To the Editor: I read with interest the article by Klasa et al1 in the December 15, 2002 issue. In a phase III study, the authors compared fludarabine to cyclophosphamide, vincristine, and prednisone (CVP) in recurrent low-grade lymphomas. An improvement in progression-free survival and treatment-free survival with fludarabine was demonstrated. Peripheral neuropathy was more common with CVP. Are these results surprising? Approximately 39% of the patients in the CVP group had received two to four prior regimens. In other words, a vast majority of patients had received a high cumulative dose of alkylating agents. Moreover, 40% had received cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP). Thus, there was an increased probability of resistance to CVP. Several small phase II studies of new combination regimens published in the 1980s had shown promising results, particularly those comprising mitoxantrone,2 epirubicine,3 or the combination of ifosfamide and etoposide,4 displaying response rates ranging from 63% to 81%. Perhaps these combinations would have been more interesting than CVP, the choice of which, based on the investigators’ habits, might be questionable. Nevertheless, the similar overall survival in both arms might reflect the heavy pretreatment of the studied population. The decline in social functioning score in the CVP group might be owing to a poorer control of the disease, but also to peripheral neuropathy by accumulation of vincristine. Psychological issues must also be taken into account since patients of the fludarabine group should have been aware of receiving a promising new drug. Since the first report of 26 cases of relapsed non-Hodgkin’s lymphoma by Leiby et al,5 several phase II studies published before initiation of the present study in 1993 had demonstrated the activity of fludarabine in pretreated patients, with response rates between 31% and 55%, and complete responses of approximately 15%.6–10 Moreover, these promising results led to trials of combinations with even better results that were published in 1994 and 1995.11,12 Their impact undoubtedly played a role in the recruitment difficulties, which led to the study’s premature halt in 1996. In conclusion, this study illustrates, and this is one of its merits, that randomization should not be employed systematically. REFERENCES
1. Klasa RJ, Meyer RM, Shustik C, et al: Randomized phase III study of fludarabine phosphate versus cyclophosphamide, vincristine, and prednisone in patients with recurrent low-grade non-Hodgkin’s lymphoma previously treated with an alkylating agent or alkylator-containing regimen. J Clin Oncol 20:4649–4654, 2002 2. Jones L, Cotter FE, Lord D, et al: Phase 2 study of mitoxantrone in combination with chlorambucil and prednisolone for relapsed and refractory non-Hodgkin’s lymphoma. Hematol Oncol 8:41–45, 1990[Medline] 3. Al-Ismail SAD, Whittaker JA, Gough J: Combination chemotherapy including epirubicin for the management of non-Hodgkin’s lymphoma. Eur J Cancer Clin Oncol 23:1379–1384, 1987[CrossRef][Medline]
4. Cabanillas F, Hagemeister FB, Bodey GP, et al: IMVP-16: An effective regimen for patients who have relapsed after initial combination chemotherapy. Blood 60:693–697, 1982
5. Leiby JM, Snider KM, Kraut EH, et al: Phase II trial of 9-b-D-arabinofuranosyl-2-fluoroadenine-5'-monophosphate in non-Hodgkin’s lymphoma: Prospective comparison of response with deoxycytidine kinase activity. Cancer Res 47:2719–2722, 1987 6. Whelan JS, Davis CL, Rule S, et al: Fludarabine phosphate for the treatment of low grade lymphoid malignancy. Br J Cancer 64:120–123, 1991[Medline] 7. Hochster HS, Kim KM, Green MD, et al: Activity of fludarabine in previously treated non-Hodgkin’s low-grade lymphoma: Results of an Eastern Cooperative Oncology Study Group. J Clin Oncol 10:28–32, 1992[Abstract]
8. Redman JR, Cabanillas F, Velazquez WS, et al: Phase II trial of fludarabine phosphate in lymphoma: An effective new agent in low-grade lymphoma. J Clin Oncol 10:790–794, 1992
9. Zinzani PL, Lauria F, Rondelli D, et al: Fludarabine: An active agent in the treatment of previously-treated and untreated low-grade non-Hodgkin’s lymphoma. Ann Oncol 4:575–578, 1993 10. Hiddemann W, Unterhalt M, Pott C, et al: Fludarabine single-agent therapy for relapsed low-grade non-Hodgkin’s lymphomas: A phase II study of the German Low-grade Non-Hodgkin’s Lymphoma Study Group. Semin Hematol 7:28–31, 1993 (suppl 20)[Medline] 11. McLaughlin P, Hagemeister FB, Swan F, et al: Phase I study of the combination of fludarabine, mitoxantrone, and dexamethasone in low-grade lymphoma. J Clin Oncol 12:575–579, 1994[Abstract] 12. Zinzani PL, Bendandi M, Tura S: FMP regimen (fludarabine, mitoxantrone, prednisone) as therapy in recurrent low-grade non-Hodgkin’s lymphoma. Eur J Haematol 55:262–266, 1995[Medline]
Related Article
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2003 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
