ORLANDO, Florida-Two trials
with bortezomib (Velcade), one in
advanced non-small-cell lung cancer
(NSCLC) and the other in small-cell
lung cancer (SCLC), suggest that it
has some activity in advanced disease.
Researchers concluded that it is premature
to test bortezomib in larger
trials but that it warrants further study,perhaps in combination with other
agents, in both NSCLC and SCLC.
NSCLC Trial vs Docetaxel
In the NSCLC trial, the drug was
tested in patients with stage IIIb or IV
disease who had previously received
one round of chemotherapy (abstract
7034). This phase II trial enrolled 158patients and randomized them to either
bortezomib alone or bortezomib
with docetaxel (Taxotere).
Response rates and survival were
comparable in the two arms. Partial
responses occurred in 8% of patients
taking bortezomib alone and in 9% of
those taking bortezomib with docetaxel.
Some of the outcomes seemed
to favor bortezomib in combination
therapy-median time to progression
was 1.5 months with bortezomib alone
vs 4 months with the bortezomib/
docetaxel combination, and more patients
had stable disease on the combination
However, 1-year survival rates were
similar: 33.1% for bortezomib alone
and 38.7% for the combination. Median
survival time was 7.4 months for
patients who received bortezomib
alone and 7.8 months for those who
received the two drugs combined.
Toxicity was low and manageable on
The results show that activity of
bortezomib is comparable to that of
the current, standard drugs for second-
line therapy of NSCLC, said the
investigators, who were led by Michael
Fanucchi, MD, associate professor
of hematology and oncology, Winship
Cancer Institute, Emory University,
Atlanta. Charles Rudin, MD, PhD,
director of the lung cancer therapeutics
program at Sidney Kimmel Comprehensive
Cancer Center, agreed.
'Respectable Results' vs
These are "nice results" for bortezomib,
he said in his discussion, noting
that the outcomes are "perfectly
respectable in comparison to any of
the existing therapies," and adding, "Ithink bortezomib appears to have real
activity in this context-an exciting
Although bortezomib is probably
not ready for a large phase III trial, Dr.
Lynch said, it would be interesting to
test it in a phase II trial with other
agents, particularly with drugs targeted
at the epidermal growth factor receptor,
SWOG Study in SCLC
In the SCLC study, bortezomib
showed less activity (abstract 7047).
Conducted by the Southwest Oncology
Group (SWOG), this phase II trial
tested the drug as a single agent inpatients with extensive disease who
had received prior platinum therapy.
Patients were stratified according to
whether they were sensitive or resistant
to platinum therapy.
Only 1 of 56 evaluable patients had
a partial response and 1 had stable
disease, both in the platinum-resistant
group. The trial was stopped early
because of the poor response rates and
a higher-than-expected rate of disease
Combination Tx Advocated
The investigators, led by Jewel Johl,
MD, of the University of California,
Davis, Cancer Center, concluded thatthe results do not warrant further study
of bortezomib as a single agent in heavily
pretreated SCLC patients. Like the
NSCLC researchers, however, Dr. Johl
and his colleagues think bortezomib
could be active in combination with
other agents. They noted that the drug,
a proteasome inhibitor, has shown activity
in combination with chemotherapy
agents that trigger apoptosis in
preclinical and phase I studies.
In discussing this study, Thomas
Lynch, MD, director, Center for Thoracic
Cancers, Massachusetts General
Hospital, Boston, agreed that further
study was warranted. "I would argue
that even one response to a single agent
in this setting is a proof of principle,"
he said, adding that combinations of
bortezomib and other agents should
be tested. One such trial, investigating
bortezomib and topotecan (Hycamtin),
has already been instituted by
SWOG, the investigators said.