NEW ORLEANSIn elderly non-small-cell lung cancer (NSCLC)
patients, the combination of gemcitabine (Gem-zar) plus vinorelbine
(Navelbine) yields better survival than vinorelbine alone, according
to the final analysis of a Southern Italy Cooperative Oncology Group
(SICOG) phase III trial. Giuseppe Frasci, MD, of the National Tumor
Institute, Naples, Italy, reported the results at the 36th
Annual Meeting of the American Society of Clinical Oncology (ASCO).
The trial evaluated survival and quality of life in a comparison of
combined gemcitabine 1,200 mg/m² plus vinorel-bine 30 mg/m²
on days 1 and 8 every 3 weeks vs vinorelbine alone at the same dose
and schedule. The rationale for the study was the need for less toxic
regimens for use in elderly patients.
Many people are concerned about the use of cisplatin-based
chemotherapy in the elderly, Dr. Frasci pointed out. Studies
have found the risk of death within 30 days of chemotherapy in
patients over 70 to be many times greater than the risk in
The combination was selected based on data showing that single-agent
vino-relbine produced good response rates and median survival with
moderate toxicity, and that the activity of gemcitabine was not
impaired in an elderly subset.
Pilot studies found the combination to be safe in patients over 70,
which led to the current trial in patients aged 71 to 85 years with
stage IV NSCLC or stage III disease with malignant pleural effusion
or supraclavicular nodal involvement. Central nervous system
involvement was allowed if patients were not symptomatic.
Survival was the primary endpoint, and quality of life was validated
by a formal quality-of-life scale. The study was terminated early
because a significant benefit emerged during the interim analysis in
favor of the combination.
The study enrolled 152 patients. Dr. Frasci presented survival data
on the first 120 patients at 14-month median follow-up. At that time,
19 patients were alive in the combination arm vs 8 in the
single-agent vinorelbine control arm.
The combination regimen proved superior in that it improved survival
and maintained quality of life. Median survival was 29 weeks in the
combination arm vs 18 weeks in the control arm (P < .01).
Probable 1-year survival was about 30% in the combination arm vs
about 10% in the vinorelbine arm.
There were no complete responses in either arm. Partial responses
were noted in 22% of patients in the combination arm and 15% in the
Evidence that combination treatment maintained a better quality of
life was provided by the finding of a prolonged time to symptom
deterioration: 21 weeks for the combination vs 13 weeks for
vinorelbine alone (P = .002).
More patients in the combination arm displayed some improvement in
symptoms during treatment. In fact, the number of patients without
symptom deterioration in 6 months was double in the combination arm,
43% vs 22%. At the conclusion of therapy, 62% of
gemcita-bine/vinorelbine patients reported quality of life to be
improved or stable, compared with 40% on vinorelbine alone, Dr.
The toxicity profiles were not significantly different, although
numerically the combination arm had more neutropenia (38% vs 28%) and
thrombocytopenia (13% vs 8%).
Performance status (PS) clearly affected outcome. Among patients with
PS 2, the percentage of patients stopping treatment before two cycles
was 59%. Their median survival was 19 weeks vs 26 weeks for patients
with PS 0-1, he said.
Comparison With ELVIS Results
Dr. Frasci pointed out that the vinorelbine control arm in this study
did not fare as well as the vinorelbine arm in the earlier ELVIS
trial (Elderly Lung Cancer Vinorelbine Italian Study). In that study,
patients receiving vinorelbine plus best supportive care survived 28
weeks, compared with 21 weeks for best supportive care alone.
The easiest explanation is that the two populations are not as
similar as they appear at first glance, he suggested. The
current study, as compared to the ELVIS trial, included more patients
with brain metastases, who did particularly poorly in the vinorelbine
arm, and more patients with comor-bidities, whose survival was worse.
We can say on the basis of these results that the addition of
gemcitabine to vinorelbine produced more than a 60% increase in
median survival time, Dr. Frasci concluded.
Gemcitabine/vino-relbine is now considered first-line treatment
in the elderly with NSCLC in our group, but we dont think that
the single-agent approach should be avoided in these patients.
In fact, he said, the Italian group has begun a randomized trial to
test two single-agent armsgemcitabine or pacli-taxel
[Taxol]and two doubletsgemcitabine/vinorelbine and gemcitabine/paclitaxel.
David Gandara, MD, the sessions discussant, remarked that the
study had a number of strengths, although the sample size was small
due to early closure, and the control arm performed particularly
poorly compared to previous trials in the same population.
He said that since the trial targeted the elderly and the
comparator was vinorelbine alone, it does not establish nonplatinum
therapy or this nonplat-inum regimen as superior or even equal to
platinum-containing regimens for general use. In poor-risk
patients, he said, two potential avenues to tolerable therapy
that also provide clinical benefit are the use of nonplatinum
regimens and sequential single agents.