ReviewLong-term efficacy of the CHVmP/BV regimen used for aggressive non-Hodgkin’s lymphoma in three randomised EORTC trials
Introduction
Patients with advanced, aggressive non-Hodgkin's lymphoma (NHL) can be effectively treated with multi-agent chemotherapy. Although most (55–80%) patients below the age of 65 years will experience a complete remission (CR) after 6–8 courses of CHOP-like chemotherapy, less than 50% will be cured. Many trials have been performed, several within the European Organisation for Research and Treatment of Cancer (EORTC) [1], introducing new drugs and more aggressive approaches, with the aim of improving the outcome of this group of NHL patients. Since 1980, the CHVmP/BV scheme (eight cycles of cyclophosphamide, doxorubicin, teniposide and prednisone with bleomycin and vincristine in every cycle at the mid-interval), which contains cyclophosphamide, doxorubicin, teniposide and prednisone combined with vincristine and bleomycin, has been consistently used in three consecutive EORTC phase III trials 2, 3, 4, 5 Combining these trials resulted in a unique chance to review the efficacy of this regimen over a 20-year period. We observed remarkably large differences across the trials in long-term outcome data. By presenting our analyses, we want to underline the risk of comparing recent studies with older ones, showing the biases that can be introduced by retrospective sub-set analyses.
Section snippets
Eligibility
Between 1980 and 1999, 936 newly-diagnosed and untreated patients with advanced, aggressive NHL were registered in three prospective, phase III randomised EORTC-trials (20802, 20855 and 20901). Follow-up was missing or incomplete in 23 patients. Therefore, altogether, 913 patients could be analysed. All three trials were designed for intermediate or high-grade NHL classified by the Working Formulation (WF) as D-J [6]. Histological classification (Table 1) was performed by the local pathologist
Long-term efficacy
Out of 913 patients with advanced, aggressive NHL, 55 and 47% were still alive at 5 and 10 years, respectively (median follow-up of 8.7 (0.2–20.4) years). The median survival was 7.3 (0.2–20.4) years, with 388 (42%) patients still alive at the time of analysis. Protocol treatment was stopped in 168 (18%) patients after three cycles, showing no response; from the patients who continued protocol treatment, 63% of the patients treated with CHVmP/BV obtained a complete remission.
Randomised trials
Trial 20802 was
Discussion
Several different regimens have been applied in patients with advanced aggressive NHL. Fisher and colleagues [13] compared third generation regimens (m-BACOD, ProMACE-CytaBOM, MACOP-B) with the classical CHOP, and found no difference in outcome between all four regimens. Our findings were similar when we compared ProMACE-MOPP, as a third generation regimen, with the EORTC-based CHVmP/BV regimen. However, by adding bleomycin and vincristine to the CHVmP scheme, we improved the survival outcome
Acknowledgments
This project was partly financed by the Dutch Cancer Foundation. The help of all participating centres and local investigators is gratefully acknowledged (see the Appendix for details).
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