Correspondence
Treatment of Localized Lymphoma
N Engl J Med 2005; 352:2449-2451June 9, 2005
- Article
To the Editor:
Reyes and colleagues (March 24 issue)1 should elaborate on the disadvantages, particularly the long-term side effects, of a regimen of doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) in comparison with a regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). With an increased duration of parenteral chemotherapy (20, rather than 3, days), ACVBP has a complicated schedule and thus poses a compliance problem in nonresearch settings. Furthermore, in many centers, patients need hospitalization to ensure hydration during high-dose methotrexate therapy. ACVBP also causes more mucositis, neutropenia, and thrombocytopenia than does CHOP, and it increases the risk of myelodysplasia and leukemia.2,3 Generally, treatment with etoposide plus repetitive administration of high-dose alkylating agents is strongly leukemogenic,4 and a 20-year follow-up showed an increase in the incidence of myelodysplasia.3
Bleomycin, used with granulocyte colony-stimulating factor (G-CSF) (which is commonly needed for dose-dense therapy), may precipitate pulmonary fibrosis.5 Finally, gonadal failure — leading to infertility, osteoporosis, and impaired quality of life6 — is potentially widespread among young patients.
6 ReferencesTawee Tanvetyanon, M.D.
Loyola University Chicago Stritch School of Medicine, Maywood, IL 60153
tan73@hotmail.com 1
Reyes F ,Lepage E ,Ganem G , et al. ACVBP versus CHOP plus radiotherapy for localized aggressive lymphoma. N Engl J Med 2005;352:1197-1205
Full Text | Web of Science | Medline2
Tilly H ,Lepage E ,Coiffier B , et al. Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma. Blood 2003;102:4284-4289
CrossRef | Web of Science | Medline3
Andre M ,Mounier N ,Leleu X , et al. Second cancers and late toxicities after treatment of aggressive non-Hodgkin lymphoma with the ACVBP regimen: a GELA cohort study on 2837 patients. Blood 2004;103:1222-1228
CrossRef | Web of Science | Medline4
Kushner BH ,Heller G ,Cheung NK , et al. High risk of leukemia after short-term dose-intensive chemotherapy in young patients with solid tumors. J Clin Oncol 1998;16:3016-3020
Web of Science | Medline5
Azoulay E ,Herigault S ,Levame M , et al. Effect of granulocyte colony-stimulating factor on bleomycin-induced acute lung injury and pulmonary fibrosis. Crit Care Med 2003;31:1442-1448
CrossRef | Web of Science | Medline6
Howell SJ, Shalet SM. Spermatogenesis after cancer treatment: damage and recovery. In: Journal of the National Cancer Institute monographs. No. 34. Washington, D.C.: Government Printing Office, 2005:12-7.
To the Editor:
Reyes et al. conclude that ACVBP is superior to CHOP plus radiotherapy for the treatment of low-risk localized lymphoma. However, when the overall rates of local relapse (8.4 percent in the ACVBP group and 6.9 percent in the CHOP-plus-radiotherapy group) are evaluated in detail, it seems that ACVBP is not much better than CHOP plus radiotherapy in achieving control of local disease, which is the aim of radiotherapy. Thus, ACVBP, when compared with CHOP plus radiotherapy, improves control of distant disease but does not affect local control in patients with low-risk localized lymphoma.
Mustafa Adli, M.D.
Alper Sevinc, M.D.
Mehmet E. Kalender, M.D.
Gaziantep University Medical School, Gaziantep 27150, Turkey
adli@gantep.edu. tr To the Editor:
In the phase 3 Groupe d'Etude des Lymphomes de l'Adulte (GELA) study, reported by Reyes et al., overall and event-free survival favored the ACVBP regimen. However, local failure was more frequent in the ACVBP group (in which 26 patients had a local recurrence, vs. 22 in the CHOP-plus-radiotherapy group). The inferiority of the CHOP-plus-radiotherapy regimen was solely due to the greater number of relapses at distant sites.
In our opinion, the GELA study does not nullify the current practice of providing additional radiotherapy in early stages of aggressive lymphoma,1,2 especially since other studies have shown beneficial effects on rates of local control with radiotherapy after more intensive chemotherapy.3 As in many other malignant diseases, local control is a prerequisite for cure as long as salvage options are limited, but in general, statistical proof of this assumption will require the evaluation of many more patients.
3 ReferencesStefan Hoecht, M.D.
Wolfgang Hinkelbein, M.D.
Charité Campus Benjamin Franklin, 12200 Berlin, Germany
stefan.hoecht@charite. de 1
Miller TP ,Dahlberg S ,Cassagy JR , et al. Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin's lymphoma. N Engl J Med 1998;339:21-26
Full Text | Web of Science | Medline2
Miller T ,Leblanc M ,Spier C , et al. CHOP alone compared to CHOP plus radiotherapy for early stage aggressive non-Hodgkin's lymphomas: update of the Southwest Oncology Group (SWOG) Randomized Trial. Blood 2001;98:742a-743a abstract.
CrossRef | Web of Science3
Horning SJ ,Weller E ,Kim K , et al. Chemotherapy with or without radiotherapy in limited-stage diffuse aggressive non-Hodgkin's lymphoma: Eastern Cooperative Oncology Group study 1484. J Clin Oncol 2004;22:3032-3038
CrossRef | Web of Science | Medline
Author/Editor Response
In response to Tanvetyanon: for more than 20 years, ACVBP has been used in a multicenter setting with 50 to 80 participating centers, including community hospitals, and the results are reproducible.1 Immediate and late toxic effects of ACVBP are documented in the GELA studies cited by Tanvetyanon. In addition, a survey of 2210 patients who received ACVBP2 showed than an age greater than 60 years, an elevated lactate dehydrogenase level, and an Eastern Cooperative Oncology Group score above 1 predicted early treatment-related deaths. In our study of low-risk localized lymphoma, we observed only two episodes of grade 4 infection and no deaths from toxic effects. Thus, we believe that ACVBP is a suitable and efficient regimen in young adults.
In the GELA study of second cancers after ACVBP therapy,3 myelodysplasia occurred principally in elderly patients (P<0.001 for the comparison with younger patients). In our study in young adults, ACVBP did not increase the number of secondary cancers when compared with CHOP plus irradiation. Finally, we have not observed in the GELA studies a significant number of cases of pulmonary fibrosis as a result of concomitant administration of G-CSF and bleomycin.4
In response to Hoecht and Hinkelbein and to Adli and colleagues: the CHOP-plus-radiotherapy group did have more relapses at distant sites than did the ACVBP group, and this discrepancy translated into a significant difference in the overall number of relapses (78 in the CHOP-plus-radiotherapy group vs. 42 in the ACVBP group). Notably, most patients in the study (67 percent) had stage 1 disease, indicating that local control by irradiation is not sufficient to ensure cure. This conclusion was also reached in the report5 cited by Hoecht and Hinkelbein, the authors of which state that “adjuvant radiotherapy provides excellent local control, but systemic relapse represents the major cause of treatment failure.” We believe that the goal of any first-line treatment of localized lymphoma is to improve survival rather than to control local disease; in our study, 89 deaths were related to progressive lymphoma, 60 of which occurred after CHOP plus radiotherapy. In addition, chemotherapy alone has the advantage of avoiding the long-term sequelae of irradiation, particularly in the frequently involved cervical nodes and Waldeyer's ring. Finally, we assume that the addition of anti-CD20 immunotherapy to chemotherapy should further improve our results, and for this reason we do not recommend adjuvant radiotherapy as first-line treatment.
5 ReferencesFélix Reyes, M.D.
Hôpital Henri Mondor, 94010 Créteil, France
felix.reyes@hmn. ap-hop-paris. fr Hervé Tilly, M.D.
Centre Henri Becquerel, 76038 Rouen, France1
Coiffier B ,Reyes F . Best treatment of aggressive non-Hodgkin lymphoma. Oncology 2005;19:Suppl:7-15
Medline2
Dumontet C ,Mounier N ,Munck JN , et al. Factors predictive of early death in patients receiving high-dose CHOP (ACVB regimen) for aggressive non-Hodgkin's lymphoma: a GELA study. Br J Haematol 2002;118:210-217
CrossRef | Web of Science | Medline3
Andre M ,Mounier N ,Leleu X , et al. Second cancers and late toxicities after treatment of aggressive non-Hodgkin lymphoma with the ACVBP regimen: a GELA cohort study on 2837 patients. Blood 2004;103:1222-1228
CrossRef | Web of Science | Medline4
Bastion Y ,Reyes F ,Bosly A , et al. Possible toxicity with the association of G-CSF and bleomycin. Lancet 1994;343:1221-1222
CrossRef | Web of Science | Medline5
Horning SJ ,Weller E ,Kim K , et al. Chemotherapy with or without radiotherapy in limited-stage diffuse aggressive non-Hodgkin's lymphoma: Eastern Cooperative Oncology Group study 1484. J Clin Oncol 2004;22:3032-3038
CrossRef | Web of Science | Medline
