CHIBA, JapanCombining either irinotecan (Camptosar) or
vindesine with cis-platin (Platinol) produced similar objective
responses and survival rates in patients with stage IIIB or IV
nonsmall-cell lung cancer, according to final results of a
Yuichi Takiguchi, MD, PhD, research associate in the Department of
Chest Medicine, Chiba University School of Medicine, told ONI
that differences in tumor response and survival seen with the two
regimens were not statistically significant. The irinotecan/cisplatin
combination had a little bit higher response rate, he
said, but the survival rate with the vindesine regimen was slightly
better. The irinotecan/cisplatin combination, he concluded, achieved
results comparable to those with cisplatin and vindesine, a regimen
previously shown to be active in advanced nonsmall-cell lung cancer.
In the phase III trial conducted from June 1995 to October 1997, 104
patients were randomized to receive cisplatin 80 mg/m² on day 1
and irinotecan 60 mg/m² on days 1, 8, and 15 of 28-day cycles.
The same dose of cisplatin was given to a comparative group of 106
patients on day 1 of a 28-day schedule along with 3 mg/m²
vindesine on days 1, 8, and 15.
The two groups were well matched, Dr. Takiguchi reported. The median
age being 62 in the irinotecan/cisplatin group and 64 in the
vindesine/cisplatin group. Eligibility criteria for the study limited
enrollment to patients with stages IIIB and IV nonsmall-cell
lung cancer with no symptomatic brain metastases and no prior
therapy. In all, 41% had stage IIIB disease and 59% stage IV. The
ECOG performance status was 0-1 for 94% of the patients, and 2 for
Evaluations for efficacy and toxicity were possible in 98 of the
patients receiving the treatment that included irinotecan and in 101
of those given vindesine along with cisplatin, Dr. Takiguchi
reported. Objective tumor responses were recorded for 28 of the
patients receiving irinotecan and cisplatin (29%), compared with 22
of those receiving vindesine and cisplatin (22%).
Survival and Toxicity
Median survival was 45 weeks in the irinotecan group and 50 weeks in
the vindesine cohort, Dr. Takiguchi said. One-year survival rates
were 43% with irinotecan and 48% with vindesine, he added. The
two-year survival rates were 14% and 20%, respectively.
The toxicity profiles did differ significantly, Dr. Takiguchi told ONI.
Cisplatin plus vindesine gave a higher incidence of
neutropenia and leukopenia, he said, and CPT-11
[irinotecan] plus cisplatin showed a higher incidence of
diarrhea. Grade 4 neutropenia was seen in 50% of patients on
the vindesine regimen, compared to 18% of those given irinotecan.
Grades 3 and 4 diarrhea occurred in 13% of patients receiving
irinotecan but only 1% of those given vindesine along with cisplatin.
Two treatment-related deaths occurred with the irinotecan regimen.
The cisplatin/irinotecan combination will be studied in another trial
planned by Japanese investigators, Dr. Takiguchi said. The
multicenter study will assign patients to four different treatment
regimens. The other three regimens to be tested are carboplatin/paclitaxel
(Taxol), cisplatin/gemcitabine (Gemzar), and cisplatin/vinorelbine
(Navelbine) combinations. The rationale for proceeding with further
testing of the cisplatin/irinotecan regimen, Dr. Takiguchi explained,
is based on the results of the study he described and another one
reported at the conference by Takefumi Komiya, MD, of Kinki
University School of Medicine, Osaka. The important point, Dr.
Takiguchi stated, is that neither of these two studies showed the
irinotecan/cisplatin combination to be inferior.