LUGANO, SwitzerlandYounger patients with histologically
aggressive, stage IV non-Hodgkins lymphoma (NHL) might benefit
from a dose-intense etoposide-containing regimen, according to late
follow-up results from the British National Lymphoma Investigation
(BNLI) reported at the VII International Conference on Malignant Lymphoma.
Between 1987 and 1991, the BNLI group randomized 459 patients with
stage II to IV diffuse large-cell or mixed-cell lymphoma to receive
either at least six cycles of a 2-weeks-on, 2-weeks-off CHOP
(cyclophosphamide, doxorubicin [Adriamycin], Oncovin [vincristine],
and prednisone) regimen or 12 weeks of therapy with a multiagent
weekly regimen called PACEBOM.
The PACEBOM regimen, an adaption of MACOP-B with lower doses of
prednisone and methotrexate and the addition of etoposide, consisted
of prednisone, Adriamycin, cyclophosphamide, etopo-side (150
mg/m² on day 1), bleomycin, Oncovin, and methotrexate.
The complete remission rates in the two arms of the trial were 57%
with CHOP and 63% with PACEBOM, a difference that is not significant,
reported Professor David Linch, of University College, London.
If one looks at the overall survival curve, updated to May
1999, there is an apparent benefit for PACEBOM, but this is not
statistically significant, Dr. Linch added. However, he pointed
out, given that many participants were sexagenarians at the start of
the trial 11 years ago, it is not surprising that some of these
elderly patients have since succumbed to causes other than lymphoma.
In contrast, PACEBOM produced a highly significant gain in
cause-specific survival among patients under the age of 50 who had
stage IV disease. Likewise, 8-year overall survival in this subgroup
was significantly prolonged by PACEBOM treatment.
I fully appreciate that these types of retrospective subgroup
analyses must be treated with great caution, Dr. Linch
acknowledged. This study does not prove that PACEBOM is better
than CHOP in younger patients with poor-prognosis disease, but it is
suggestive, he emphasized. To confirm the possible benefit, he
observed, it will be necessary to conduct separate, large-scale
trials of dose-intensive chemotherapy in high-risk patients.
Multiagent, conventional-dose therapy, particularly regimens
that contain etoposide, should not be discarded as having no hope for
the future, Dr. Linch said, adding that the results of
additional studies incorporating etoposide should be forthcoming in
the near future.