The EORTC strategy in the treatment of Hodgkin's lymphoma

Eghbali et al.
aggressive and more extensive treatment in U cases
according to response and prognostic factors. All
early stages (still according to Ann Arbor criteria)
in the H10F group will be treated by a front line
chemotherapy, those who are not in CR after two
cycles of chemotherapy as determined by FDG–
PET scan, will be treated according to a different
scheme than those who are in CR. Early complete
remitters after two cycles of the front-line chemotherapy
will be treated with chemotherapy only in
the experimental arm, whereas the standard arm
still uses the combined modality treatment regardless
of the results of the FDG–PET scan after two
cycles. Those in the F10U group will have the same
approach with PET-scan but with more chemotherapy.
Hence in this trial the old prognostic
system is combined with a new dynamic factor,
namely early response, and radiotherapy fields and
dose are simultaneously discussed with a newly
definition of involved lymph node field instead of
involved area.
At the other side of the spectrum, in the
advanced stages the general trend was to intensify
the treatment burden to overcome disease aggressiveness.
The Lymphoma Group had compared
MOPP to alternating MOPP and ABVD followed
by optional radiotherapy (icebergs). This trial
aimed to compare the new concept of alternating
chemotherapy to the standard (MOPP), but there
was any addressed question about radiotherapy
(19). Later Cannellos and co-workers demonstrated
that this alternating scheme gives the same results
as hybrid MOPP/ABV and ABVD (25) leading to
the final conclusion that ABVD could be considered
as standard in advanced stages. The question
of radiotherapy’s role in patients with CR after
chemotherapy was raised by the EORTC Lymphoma
Group in its trial H3 and H4 (trial 20884).
All patients with stage III or IV had front line
MOPP/ABV. Those in CR after four courses had
two more cycles and were randomised between
24 Gy involved field radiotherapy and observation.
Others had four more cycles and were randomised
after eight courses in the same way. All partial
remitters were systematically irradiated on their
initial involved fields (40 Gy) and progressions
were put off-study. After a median follow-up of
8 yr it appeared that complete remitters had no
advantage from additional radiotherapy, complete
remission after efficacious chemotherapy proved to
be enough treatment in advanced stages (26, 27). In
this study however there was no selection according
to prognostic factors and F cases were treated in
the same way as the U ones. The retrospective
analysis according to Hasenclever and Diehl (28)
showed little help in dividing the very good and the
worst cases. The latter is commonly known to have
a very bad outcome. For a better result, if any, we
began a trial comparing eight cycles of standard
ABVD to an association of four escalated BEA-
COPP followed by four standard BEACOPP. This
inter-group trial in conjunction with the GELA and
other international collaborative groups (Nordic
group, NCI Canada, British BNLI, Australian
Lymphoma Group, Spanish Groups GELCAB
and PETHEMA) is currently running.
However, all these trials in early stages or
advanced stages use old drugs and even old
regimens. The AVBD was framed by Bonadonna
more than 30 yr ago (29) and nothing else since has
made this regimen obsolete. Every physician dealing
with HD knows its advantages and its toxicity
and limits. New regimes are probably needed. Here
also the limit is the high rate of cure, which makes
any trial in standard cases non-ethical. In the
elderly however there is a subset of patients with
aggressive HD (stages III and IV) that is unable to
have BEACOPP, at least with full dosage. For such
patients, the Lymphoma Group in collaboration
with the German Hodgkin Study Group began a
trial using gemcitabine instead of bleomycin and
prednisone instead of dacarbazine in the ABVD
regimen. Whether this new regimen (named PVAG)
with this new drug will be effective and non-toxic is
too early to know since this subset is very rare and
the trial too recent.
The HD is a continuous challenge for our minds. It
was a long time ago the scheme of combined
modality treatments in oncology for solid tumours
and still remains a leading example of treatment
management, for a better treatment combining lesser
toxicity and more efficacy. The EORTC Lymphoma
Group is deeply involved in this and currently has
joined other groups to face new challenges that
appear recently along with new social, economic,
medical, and politic conditions (30).
References
1. Noordijk EM, Carde P, Mandard AM, et al. Preliminary
results of the EORTC-GPMC controlled trial H7 in earlystage
Hodgkin’s disease. EORTC Lymphoma Cooperative
Group, Groupe Pierre-et-Marie-Curie. Ann Oncol
1994;5(Suppl. 2):S107–S112.
2. Hagenbeek A, Carde P, Noordijk E, Thomas J, Tirelli
U, Monconduit M, Eghbali H, Mandard AM, Henry-
Amar M. Prognostic factor tailored treatment of early
stage Hodgkin’s disease. Results from a prospective randomized
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nodal irradiation in favorable clinical stage I-II Hodgkin’s
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