Hybrid Chemotherapy Boosts Survival Time in Advanced HD

LUGANO, Switzerland—ChlVPP/EVA hybrid chemotherapy proved more effective than both MVPP and VAPEC-B as first-line treatment for advanced Hodgkin’s disease (HD) in two collaborative studies, Dr. John A. Radford, of Christie Hospital, Manchester, UK, reported at the VII International Conference on Malignant Lymphoma. The hybrid regimen consists of chlorambucil, vinblastine, procarbazine, and prednisone plus etoposide, vincristine, and doxorubicin (Adriamycin).

High-Risk Patients

In the first trial, conducted at two UK centers, 419 high-risk patients with either stage I/II disease associated with B symptoms and/or mediastinal bulk or stage III/IV disease were randomized to treatment with eight 42-day cycles of MVPP (mechlorethamine, vinblastine, procarbazine, and prednisone) or eight 28-day cycles of the hybrid regimen (Ch1VPP/EVA-1). After completing chemotherapy, patients underwent radiotherapy for bulky or residual disease.

Complete response was achieved in 68% of patients who received the hybrid regimen, compared with 55% of those treated with MVPP. “Those results, after a median follow-up of 9½ years, translate into significant improvement in freedom from progression and event-free survival, but no significant difference at this time in overall survival,” Dr. Radford said.

For the second trial, 282 patients recruited at three UK centers and one Italian center were randomized to receive either six 28-day cycles of the hybrid regimen (Ch1VPP/EVA-2) or 11 weekly cycles of a VAPEC-B regimen (vincristine, Adriamycin, prednisone, etoposide, cyclophosphamide, and bleomycin) plus prophylactic ketocon-azole (Nizoral) and co-trimoxazole, followed by radiotherapy when necessary. This trial was stopped prematurely, however, after the second planned interim analysis.

“After a median follow-up of 3½ years, there was a marked freedom-from-progression advantage for the ChlVPP/EVA hybrid, compared with VAPEC-B (approximately 80% vs 60%),” Dr. Radford said. “The event-free survival shows a similar difference between the two regimens, and there is also a difference in overall survival (approximately 95% vs 78%, P = .03).”

Comparison of the ChlVPP/EVA-1 variant used in the first trial with the Ch1VPP/EVA-2 variant used in the second trial revealed no significant differences in freedom from progression or event-free survival, although there was a trend toward better overall survival with Ch1VPP/EVA-2.

“The ChlVPP/EVA hybrid is an effective regimen for the primary treatment of Hodgkin’s disease and is superior to MVPP in terms of freedom from progression and event-free survival, and markedly better than weekly VAPEC-B therapy,” Dr. Radford concluded.

Pooled data from both trials indicated that, at 5 years, the hybrid regimen was associated with 79% freedom from progression, 73% event-free survival, and 83% overall survival. “We have observed second malignancies, and their actuarial incidence was 4% at 5 years and 7% at 10 years,” Dr. Radford said.

Ongoing UK Study

In an ongoing UK study, the Ch1VPP/EVA hybrid regimen evaluated in these two trials is being compared with ABVD (Adriamycin, bleomycin, vindesine, and dacarbazine) and with ChlVPP/PABLOE (prednisone, Adriamycin, bleomycin, Oncovin, etoposide), an alternating therapy developed by the British National Lymphoma Investigation group.

“The next step is to try to identify very-high-risk groups of patients because we would be very keen to limit toxicity for those who can do well with a simpler therapy, while giving maximal treatment to those who really need it,” Dr. Radford commented.