Superiority of Chemotherapy Alone with the ACVBP Regimen over Treatment with Three Cycles of CHOP Plus Radiotherapy in Low Risk Localized Aggressive Lymphoma: The LNH93-1 GELA Study

Reviewer: Ryan Smith, MD
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Last Modified: December 9, 2002

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Presenter: Felix Reyes
Presenter's Affiliation: GELA
Type of Session: Scientific

Background

    Chemoradiation is likely the most common form of treatment in patients with aggressive but localized Non-Hodgkin's Disease (NHL). However, published series appear heterogeneous with respect to prognostic factors. There is the possibility that patients could benefit from more aggressive chemotherapy. Therefore, this study was done to compare more aggressive chemotherapy with more traditional chemoradiation.

Materials and Methods

  • 647 patients, under the age of 60, with Stage I-II aggressive histology NHL were enrolled in the study
  • 598 were eligible (most disqualified after central pathologic review)
  • 67% had stage I disease
  • 86% had diffuse large B cell histology
  • 80% of cases had peripheral nodal involvement, usually with Waldeyer's ring.
  • Over 40% had extranodal disease
  • 10% had bulky disease Arm 1:ABCVP chemotherapy (doxorubicin 75 mg/m2 day 1, cyclophosphamide 1.2 g/m2 day 1, vindesine 2mg/m2 days 1 and 5, bleomycin 10mg days 1 and 5, prednisone 60 mg/m2 day 1 to 5) given every 2 weeks x 3 followed by a consolidation chemotherapy regimen consiting of methotrexate, ifosfamide, VP16 and cytarabine.
  • Arm 2-CHOP x 3 followed by involved field radiation therapy to 40 Gy at 1.8 cGy 5 times per week.
  • Median follow up was 60 months

Results

  • CR was 93% in each group
  • 5 yr Event Free Survival (EFS) was 82% vs 64%, p=.009, favoring the ACVBP group
  • Overall survival (OS) was also better in the ACVBP group (89% vs. 80%, p=.02)
  • Factors decreasing the EFS included bulky disease, Stage II disease, and the CHOP + RT treatment arm.
  • Pattern of failure was somewhat different, as 40% failed locally in the ACVBP arm compared to 20% in the CHOP + RT arm. 60% failed distally in the ACVBP arm vs. 80% in the CHOP + RT arm.
  • The ACVBP arm was more toxic, requiring more G-CSF support, a 20% hospitalization rate in each cycle, and a 4% Grade 3 infection rate
  • Median survival after relapse was 22 mo (ACVBP) and 12 months (CHOP + RT)

Author's Conclusions

  • Patients less than 60 years old with localized aggressive lymphoma have better outcomes when treated with the ACVBP regimen, as compared to CHOP + RT.
  • Primary relapses and treatment failures have a poor prognosis, so work should continue to improve the EFS and OS

Clinical/Scientific Implications

    Though there is no one standard of care for localized aggressive NHL, the best results have been with combined chemotherapy (CHOP) plus radiation therapy. This has the added benefit of decreasing the intensity of both regimens, hence decreasing the toxicity of each. This study shows the surprising result that aggressive chemotherapy is superior to classic CHOP + RT in young patients with localized aggressive NHL. The explanations for this are many, and will likely not be able to be finalized until the full manuscript with full treatment parameters is published. As stated in the author's presentation, the greatest difference in efficacy was seen in those patients with bulky disease. Given that the local control was still better in the group that used radiation and that more patients failed distally, this points to the fact that 3 cycles of CHOP is merely not enough chemotherapy in these patients. This is supported by historical data (mainly by SWOG) that shows that Stage II bulky disease do just as poorly as patients with more advanced (Stage III-IV) disease. When patients with nonbulky disease were evaluated separately, the EFS curves come closer together and there is no difference in overall survival. Since patients with bulky disease only comprised 10% of the patient population, most if not all of the differences must have been contained in these patients with bulky disease. Also, data on type and amount of radiation therapy was not presented in the abstract or presentation. This could obviously greatly skew the data to the more aggressive chemotherapy arm. Further questions remain, such as combining more aggressive chemotherapy with radiation therapy and the treatment for bulky disease. Until the full manuscript is published, the conclusions that can be made include the fact that CHOP x 3 is inadequate in patients with bulky disease and that aggressive chemotherapy is associated with good results, but a fairly high toxicity. Whether ACVBP chemotherapy is superior to CHOP + RT is as of yet, unknown, and further follow up and full description of the treatment parameters is needed.

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