Systematic review of purine analog treatment for chronic lymphocytic leukemia: lessons for future trials
| Autor: | Bauduer, M., Gribben, J., Herrmann, R., Thiel, E., Rai, K., Larson, R., Ferrara, F., Barnard, J., Pearce, H., Taylor, C., Brillant, B., Steurer, M., Weingart, O., Flinn, W., Funkhouser, A., Nallman, M., Sun, Z., Jakšić, Branimir, Suciou, S., Chevret, S., Dighiero, G., Leporrier, M., Frankel, S.R., Sirard, C., Hillmen, P., Trehu, B., Felder, M., Busch, R., Eichorst, B., Mallek, M., Stilgenbauer, S., Pangalis, G., Bezares, R., van Oers, M.H.J., van Putten, W., Gobbi, M., Spriano, M., Mabed, M., Catovsky, D., Richards, S., Wade, R., Abdelhamid, T., Dearden, C., Knauf, W., Blonski, J., Jamroziak, K., Robak, T., Mauro, F., Hiddeman, W., Johnson, S.A., Longthorne, G., Rummel, M.J., Juliusson, G., Pulluqui, P., Zinzani, P.L., Pozzato, G., Reynolds, C, Furman, R.R., Durrant, J., Elphinstone, P., Evans, V., Gettins, .L, Hicks, C., James, S., Clarke, M., MacKinnon, L., McHugh, T.M., Morris, P., Read, S., Gregory, C. |
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| Přispěvatelé: | Pozzato, Gabriele, Bauduer M, Gribben J, Herrmann R, Thiel E, Rai K, Larson R, Ferrara F, Barnard J, Pearce H, Taylor C, Brillant C, Steurer M, Weingart O, Flinn IW, Funkhouser A, Tallman M, Sun Z, Jaksic B, Suciu S, Chevret S, Dighiero G, Leporrier M, Frankel SR, Sirard C, Hillmen P, Trehu B, Felder M, Busch R, Eichhorst B, Hallek M, Stilgenbauer S, Pangalis G, Bezares R, van Oers MH, van Putten W, Gobbi M, Spriano M, Mabed M, Catovsky D, Richards S, Wade R, Abdelhamid T, Dearden C, Knauf W, Blonski J, Jamroziak K, Robak T, Mauro F, Hiddeman W, Johnson SA, Longthorne G, Juliusson G, Pulluqi P, Zinzani PL, Pozzato G, Oncology US, Reynolds C, Furman RR, Durrant J, Elphinstone P, Evans V, Gettins L, Hicks C, James S, Clarke M, MacKinnon L, McHugh TM, Morris P, Read S, Gregory C. CLL Trialists’ Collaborative Group |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Oncology
medicine.medical_specialty review Purine analogue chronic lymphocytic leukemia fludarabine clinical trial Pharmacology Disease-Free Survival combination therapy purine analog Internal medicine Antineoplastic Combined Chemotherapy Protocols Medicine Humans Progression-free survival Cladribine Antineoplastic Agents Alkylating Chlorambucil business.industry Hematology Odds ratio Leukemia Lymphocytic Chronic B-Cell Fludarabine Clinical trial Treatment Outcome CLL cyclophosphamide Purines Original Articles and Brief Reports business Untreated Chronic Lymphocytic Leukemia medicine.drug |
| Popis: | Background. A systematic review of purine analogs revealed heterogeneity between trials in treatment effects on response and progression free survival, but not survival, perhaps partly due to variations in analysis methods. In addition, combination treatments required evaluation. Design and Methods. Individual patient data were sought for all randomized trials in untreated chronic lymphocytic leukemia which involved a purine analog, but not including antibody therapies. Results. Sixteen trials were found, addressing seven comparisons. Eight trials, with 2753 patients, showed that single agent purine analog improved progression free survival (Odds ratio = 0.71; 95% confidence interval =0.63-0.79). Heterogeneity remained substantial. Three trials, with 1403 patients, showed that progression free survival was further improved by the addition of cyclophosphamide (Odds ratio = 0.54; 0.47-0.62). Fewer data were available on the addition of other drugs to purine analog, and none showed clear benefit. Two trials, with 544 patients, suggested cladribine improved progression free survival compared to fludarabine (Odds ratio = 0.77; 0.63-0.95). No differences were seen in overall survival for any comparisons. Conclusions. Purine analogs, particularly combined with cyclophosphamide, significantly improve progression free survival but not survival. Some groups, such as the elderly, may not see the same benefits and maximising doses may be important for all treatments, including chlorambucil. Longer follow-up, consistent definitions and detailed reporting of trials should be encouraged. |
| Databáze: | OpenAIRE |
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