LOS ANGELES, June 1 —
Celebrex (celecoxib), the Cox-2 inhibitor, and
Tarceva(erlotinib), the epidermal growth factor-receptor (EGFR) inhibitor,
have been teamed with some preliminary success to inhibit late-stage
non-small-cell lung cancer.
Action Points- Advise patients who ask that resistance to the cancer drug Tarceva is thought to involve over-expression of cyclooxygenase-2; and the Cox-2 inhibitor Celebrex therefore might prove useful in treatment.
- Note
that in this preliminary, small study, the drug combination was safe
and produced a clinical response in 33% of patients, more than would be
expected with Tarceva alone.
Over-expression of Cox-2 in tumor cells was seen in preclinical studies to cause resistance to drugs like
Tarceva,
which block tumor cell growth by targeting the EGFR, according to Karen
Reckamp, M.D., of the University of California at Los Angeles.
Dr. Reckamp and colleagues hypothesized that combining Celebrex with Tarceva
would improve response rates; and they initiated a Phase I study to
find the optimal biological dose and establish the toxicity profile of
the combination.
As a secondary endpoint, the researchers included clinical response to the drug pairing.
Typically, Dr. Reckamp said, about one patient in 10 responds to Tarceva alone. Yet with the combination, 33% had a partial clinical response, and an additional 24% achieved stable disease.
"Tarceva
alone is a great drug and has a lot of clinical benefits, but for a
small proportion of patients," Dr. Reckamp said. "With this drug
combination, we saw an increase in response rates, indicating we are
overcoming some resistance."
In the June 1 issue of Clinical Cancer Research,
Dr. Reckamp and colleagues presented safety data on 21 participants
with stage IIIB and/or IV non-small-cell lung cancer, who received
increasing doses of Celebrex, from 200 mg to 800 mg twice daily, as well as 150 mg/day of Tarceva.
The
most common toxicities were rash and skin-related effects, reported by
86% of patients, but there were no dose-limiting toxicities and no
cardiovascular toxicities related to the study drugs, the researcher
found.
One patient—in the group taking 200 mg twice daily of Celebrex—suffered
a myocardial infarction, but the event was after he stopped taking the
drug and thought to be unrelated, because he had a previous history of
MI. He had been enrolled before the spate of warnings about
cardiovascular risks of Celebrex.
The optimal dose of Celebrex, measured by decrease in urinary prostaglandin E-M, was 600 mg twice a day.
The researchers also reported response data for 21 of the patients; the other patient had his Celebrex interrupted following the FDA warning regarding cardiovascular safety.
The
researchers evaluated response rates after eight weeks, but patients
stayed on the study until tumor progression. The longest duration of
response was 95 weeks, Dr. Reckamp said, which is more than three times
longer than the average duration of response for a patient with
advanced lung cancer.
The
researchers are planning a Phase II study, expected to start later this
year, to confirm the efficacy of the combination therapy and to try to
increase their understanding of Tarceva resistance, Dr. Reckamp said.
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发表于 2007-7-25 09:51:10
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发表于 2007-7-28 18:08:02
