TORINO, Italy-Combination
therapy with gefitinib (Iressa) and
gemcitabine (Gemzar) produced disease
control in 45.7% of elderly patients
with advanced non-small-cell
lung cancer (NSCLC), according to
Giorgio V. Scagliotti, MD, of the University
of Turin, Torino, Italy, reporting
results of a phase II Italian
multicenter study (abstract 7081). The
study also found that patients were
better able to tolerate gefitinib/gemcitabine
than a gefitinib/vinorelbine
(Navelbine) combination.
The study included 59 elderly patients
with chemonaive stage IIIB/IV
NSCLC. All patients were treated with
gefitinib (250 mg/day orally until progression),
plus either vinorelbine
(30 mg/m2 IV, arm A) or gemcitabine
(1,200 mg/m2 IV, arm B). For unexplained
reasons, the two study arms
differed in a number of characteristics.
Male patients accounted for 58%
of arm A vs 80% of arm B, and squamous
histology characterized 17% of
arm A vs 31% of arm B.
Drugs were given on days 1 and 8
every 21 days for six cycles. The primary
endpoint was response rate.
Arm A was closed after 21 of the
first 24 patients (87.5%) had grade 3
or 4 adverse events, Dr. Scagliotti re
ported. These included 72% grade 3
or 4 neutropenia and treatment-related
deaths (one sudden cardiac arrest,
one grade 4 neutropenia with septic
shock
and cerebral infarction, and one
grade 4 diarrhea followed by cardiac
arrest).
"Of the 12 nonevaluable patients, 6
had withdrawn from the study, 5 had
died, and 1 had an unconfirmed diagnosis
of NSCLC," Dr. Scagliotti said.
In both arms, the most common
gefitinib-related adverse event was skin
toxicity, mainly grade 1-2. In arm B,
11.4% of patients experienced grade 3-
4 neutropenia and 8.6% had thrombocytopenia
, compared with 0 in arm A.
Grade 3-4 asthenia and diarrhea were
more common in arm A, with both
those adverse events occurring among
12% in arm A vs 5.7% in arm B. Dr.
Scagliotti also reported one case of grade
4 elevated transaminase levels.
Responses and Duration
Among the 27 patients in arm A
(gefitinib/vinorelbine) 1 (4%) had a
complete response (CR), 3 (12%) had
partial responses (PR), 7 (28%) had
stable disease (SD), 6 had progressive
disease (PD), and 7 patients were not
evaluable (see Table 1). Median duration
of response on arm A was 274
days; median time to progression
(TTP) was 91 days; median survival
was 371 days; and 63% of patients
were alive at 6 months.
Responses and Duration
Among the 27 patients in arm A
(gefitinib/vinorelbine) 1 (4%) had a
complete response (CR), 3 (12%) had
partial responses (PR), 7 (28%) had
stable disease (SD), 6 had progressive
disease (PD), and 7 patients were not
evaluable (see Table 1). Median duration
of response on arm A was 274
days; median time to progression
(TTP) was 91 days; median survival
was 371 days; and 63% of patients
were alive at 6 months.
"In elderly patients with advanced
NSCLC, vinorelbine plus gefitinib was
active but toxicity was unacceptable,
while gemcitabine plus gefitinib was
safe, and a remarkable percentage of
patients achieved disease control," Dr.
Scagliotti concluded.
