ChIVPP/EVA Regimen Is Effective in Advanced Hodgkin's Disease

LUGANO, Switzerland—In previously untreated, advanced Hodgkin’s disease, the ChIVPP/EVA regimen, though associated with risk of sterility, is highly effective with a low incidence of secondary leukemias, according to a recent analysis of two randomized studies.

The studies, both of which include a large number of patients with long follow-up, hint at the potential role for this more intensive, etoposide-containing chemotherapy regimen alongside the current world standard of ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine), according to Dr. John A. Radford, professor of medical oncology, Christie Hospital, Manchester, UK.

"It would be wrong to say that one particular treatment is the treatment for advanced Hodgkin’s disease," Dr. Radford said. "I think there will be a portfolio of therapies that will be used to try to match therapy to illness more closely, and I think this is something that is going to develop over the next few years."

At the 8th International Conference on Malignant Lymphoma (ICML abstract 207), Dr. Radford presented an analysis of two consecutive randomized trials of ChIVPP/EVA vs a comparator. The trials included 701 patients with previously untreated stage III/IV Hodgkin’s disease.

In the first trial, initiated in 1984, 419 patients received either the then-standard MVPP regimen (mechlorethamine, vinblastine, procarbazine, prednisone) on a 42-day cycle, or the etoposide-containing regimen, which included chlorambucil, vinblastine, procarbazine and prednisolone (ChIVPP) orally on days 1 to 7, followed by etoposide, vincristine, and Adriamycin (EVA) on day 8 of a 28-day cycle. Treatments were given for 6 to 8 cycles.

Results, published in 1995 in the Journal of Clinical Oncology (Radford JA et al: 13:2379-2385, 1995), showed that ChIVPP/EVA-treated patients had superior freedom from progression, event-free survival, and overall survival, with fewer secondary cases of acute myelogeous leukemia (AML) or myelodysplastic syndrome (2 cases vs 8 for MVPP) with a median follow-up of 12.5 years.

The second trial compared 11 weeks of VAPEC-B chemotherapy (vincristine, Adriamycin, prednisolone, etoposide, cyclophosphamide, bleomycin) with 6 months of ChIVPP/EVA in 282 patients enrolled beginning in 1992. The goal was to determine whether the VAPEC-B regimen, shorter and with relatively low toxicity, was at least as effective as ChIVPP/EVA chemotherapy.

Results at 4.9 years median follow-up have just been published (Radford JA et al: J Clin Oncol 20:2988-2994, 2002), showing that the ChIVPP/EVA regimen was associated with significantly better freedom from progression (82% vs 62%), event-free survival (78% vs 58%), and overall survival (89% vs 79%) at 5 years.

"The results we obtained with ChIVPP/EVA were at least as good as those we previously saw with MVPP, so this is the second study we have done with consistently very good results obtained," Dr. Radford said.

While this trial failed to show that the shorter, less toxic VAPEC-B regimen was equivalent overall, subset analysis suggested equivalence among the patients with the best prognosis (nonbulky disease, Hasenclever score of 2 or less).

Pooled Analysis

A pooled analysis of the two trials (median follow-up of 9.4 years, including 355 ChIVPP/EVA-treated patients), shows a 79% rate of freedom from progression, 72% event-free survival, and 82% overall survival at 5 years. The analysis also suggested a low incidence of secondary AML or myelodysplastic syndrome at 5 years (1%) and at 10 years (1.6%).

Dr. Radford said the ChIVPP/EVA results he reported are similar to those the German Hodgkin’s Disease Study Group have obtained recently with BEACOPP (bleomycin, etoposide, Adriamycin, cyclophosphamide, vincristine, procarba-zine, prednisone), which, unlike ChIVPP/EVA, is associated with a "worrying incidence" of secondary leukemias.

Now, the most important question for ChIVPP/EVA is how it compares to ABVD. If the two are equivalent, then ABVD will be considered the better therapy because it does not cause sterility, Dr. Radford said.

However, some investigators believe that although VAPEC-B, ABVD, and others are likely equivalent with respect to impact on low-risk disease (Hasenclever scores of 2 or lower), a more intensive therapy is required for higher-risk patients. Accordingly, Dr. Radford and his colleagues plan to launch a study of ChIVPP/EVA vs ABVD in patients stratified according to a risk analysis.

"We are trying to be more customized in terms of assessing the patient and matching the degree of adverse prognosis with the amount of treatment given," Dr. Radford said. "It may be that in worse-prognosis patients, we are not going to be able to avoid sterility—that may be just one of those unfortunate aspects of curing bad-prognosis disease."