LUGANO, SwitzerlandChlVPP/EVA hybrid chemotherapy proved more
effective than both MVPP and VAPEC-B as first-line treatment for
advanced Hodgkins 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).
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
The ChlVPP/EVA hybrid is an effective regimen for the primary
treatment of Hodgkins 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.