Comparison of Outcomes in Studies of Advanced Hodgkin's Lymphoma
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《临床肿瘤学》
Cancer Research UK Clinical Centre, Southampton General Hospital, Southampton, United Kingdom
Cancer Research UK Department of Medical Oncology, Christie Hospital, Manchester, United Kingdom
Department of Medical Oncology, Queen Elizabeth Hospital, Birmingham, United Kingdom
Medical Research Council Clinical Trials Unit, London, United Kingdom
Yorkshire Cancer Research Academic Unit of Clinical Oncology, Weston Park Hospital, Sheffield, United Kingdom
We were interested to read the editorial by Dr Carde1, which referred to our article2 that reported the results of the United Kingdom Lymphoma Group LY09 study in advanced Hodgkin's lymphoma. The editorial may have given the impression that our study was a randomized comparison of three regimens, which is not the case. A standard arm of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) was used, and investigators elected in advance whether to randomize against the alternating or hybrid regimen. Thus, it is not legitimate to make direct comparison of the two multidrug arms. It is also difficult to compare the overall results in this study to the Italian trial reported in the same issue by Gobbi et al3, which included a more favorable group of patients among whom only 11% of patients were in International Prognostic Score group 4 to 7, compared with 19% in the UK study. The measure of 65% progression-free survival at 5 years cited by Dr Carde refers only to patients in stages III/IV, whereas for the UK study as a whole the figure is 73%.
The interpretation of information regarding the use of radiotherapy in the two parallel randomizations is problematic. Dr Carde suggests that a comparison can be made between the two standard ABVD groups, with the more frequent use of eight cycles in the centers randomizing against alternating treatment apparently giving marginally better freedom from progression results than those seen in the hybrid randomization, where it was more common to use six cycles followed by radiotherapy. Such data must be interpreted with caution, especially because the patients in the hybrid randomization were more likely to have bulky mediastinal disease and systemic symptoms, suggesting a worse prognostic group. We contend that such an effect may be due to patient selection rather than the use of radiotherapy or fewer cycles of ABVD.
Finally, Dr Carde has made a provocative analysis of the data, correlating freedom from progression with intended, rather than actual doses delivered. This may be helpful in terms of generating hypotheses to be tested in future studies but does not necessarily explain observed outcomes in the LY09 trial.
REFERENCES
Carde P: The chemotherapy/radiation balance in advanced Hodgkin's lymphoma: Overweight which side J Clin Oncol 23:9058-9062, 2005
Johnson PWM, Radford JA, Cullen MH, et al: Comparison of ABVD and alternating or hybrid multidrug regimens for the treatment of advanced Hodgkin's lymphoma: Results of the United Kingdom Lymphoma Group LY09 trial. J Clin Oncol 23:9208-9218, 2005
Gobbi PG, Levis A, Chisesi T, et al: ABVD versus modified Stanford V versus MOPPEBVCAD with optional and limited radiotherapy in intermediate- and advanced-stage Hodgkin's lymphoma: Final results of a multicenter randomized trial by the Intergruppo Italiano Linfomi. J Clin Oncol 23:9198-9207, 2005(Peter W.M. Johnson , John)
Cancer Research UK Department of Medical Oncology, Christie Hospital, Manchester, United Kingdom
Department of Medical Oncology, Queen Elizabeth Hospital, Birmingham, United Kingdom
Medical Research Council Clinical Trials Unit, London, United Kingdom
Yorkshire Cancer Research Academic Unit of Clinical Oncology, Weston Park Hospital, Sheffield, United Kingdom
We were interested to read the editorial by Dr Carde1, which referred to our article2 that reported the results of the United Kingdom Lymphoma Group LY09 study in advanced Hodgkin's lymphoma. The editorial may have given the impression that our study was a randomized comparison of three regimens, which is not the case. A standard arm of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) was used, and investigators elected in advance whether to randomize against the alternating or hybrid regimen. Thus, it is not legitimate to make direct comparison of the two multidrug arms. It is also difficult to compare the overall results in this study to the Italian trial reported in the same issue by Gobbi et al3, which included a more favorable group of patients among whom only 11% of patients were in International Prognostic Score group 4 to 7, compared with 19% in the UK study. The measure of 65% progression-free survival at 5 years cited by Dr Carde refers only to patients in stages III/IV, whereas for the UK study as a whole the figure is 73%.
The interpretation of information regarding the use of radiotherapy in the two parallel randomizations is problematic. Dr Carde suggests that a comparison can be made between the two standard ABVD groups, with the more frequent use of eight cycles in the centers randomizing against alternating treatment apparently giving marginally better freedom from progression results than those seen in the hybrid randomization, where it was more common to use six cycles followed by radiotherapy. Such data must be interpreted with caution, especially because the patients in the hybrid randomization were more likely to have bulky mediastinal disease and systemic symptoms, suggesting a worse prognostic group. We contend that such an effect may be due to patient selection rather than the use of radiotherapy or fewer cycles of ABVD.
Finally, Dr Carde has made a provocative analysis of the data, correlating freedom from progression with intended, rather than actual doses delivered. This may be helpful in terms of generating hypotheses to be tested in future studies but does not necessarily explain observed outcomes in the LY09 trial.
REFERENCES
Carde P: The chemotherapy/radiation balance in advanced Hodgkin's lymphoma: Overweight which side J Clin Oncol 23:9058-9062, 2005
Johnson PWM, Radford JA, Cullen MH, et al: Comparison of ABVD and alternating or hybrid multidrug regimens for the treatment of advanced Hodgkin's lymphoma: Results of the United Kingdom Lymphoma Group LY09 trial. J Clin Oncol 23:9208-9218, 2005
Gobbi PG, Levis A, Chisesi T, et al: ABVD versus modified Stanford V versus MOPPEBVCAD with optional and limited radiotherapy in intermediate- and advanced-stage Hodgkin's lymphoma: Final results of a multicenter randomized trial by the Intergruppo Italiano Linfomi. J Clin Oncol 23:9198-9207, 2005(Peter W.M. Johnson , John)