After failure of second-line chemotherapy in patients
with metastatic NSCLC, treatment options are very limited.
Te role of salvage chemotherapy for these patients is still
unclear. The goals of salvage chemotherapy should be to
reduce tumor burden, to improve or maintain performance
status and to increase TTP and possibly prolong overall
survival. Drug efficacy has to be balanced against toxicity
and gain in the time of progression-free survival and overall
survival.
In a study reported by Ozdogan et al. [7], 16 cisplatinpretreated
NSCLC patients who received third-line chemotherapy
were evaluated retrospectively. In this study, seven
patients were treated with weekly gemcitabine, four with
taxanes, three with weekly vinorelbine, one with cisplatin+
gemcitabine, and one with docetaxel+vinorelbine. The
authors reported a partial response in one (6.2%) patient
who was treated with weekly gemcitabine and stabile
disease in four (24.8%) patients. The median time to
progression and the median overall survival was 46 days
and 132 days, respectively.
Single-agent vinorelbine also has been used in the
second-line treatment in patients with advanced NSCLC,
and variable and conflicting results have been reported. In
Santoro et al.'s study [8], VNB produced objective responses
in 20% of previously treated NSCLC patients whereas in
two other studies no responses were reported [9,10].
In our small study, the results of weekly vinorelbine as
salvage treatment for metastatic NSCLC are unsatisfactory.
No responses were observed and median TTP (44 days)
and median survival (103 days) were relatively short.
Disease stabilization was achieved in only two patients.
This poor outcome may be linked to our drug choice for
salvage therapy. Vinorelbine has similar mechanisms of
action (microtubule inhibition) and drug resistance (pglycoprotein
over-expression) with taxanes, which have
been used in second-line chemotherapy for our patients.
Since it has a different mechanism action, gemcitabine is
probably more suitable monotherapy choice among the
third-line generation chemotherapeutics. Chen et al [11]
reported a median survival time of 4.5 months in the 17 patients receiving gemcitabine as third-line therapy. They
obtained a partial response in two patients. In our series,
12 patients have received gemcitabine in combination with
taxanes for their second-line chemotherapy.
A promising new approach in third-line therapy for
NSCLC is that inhibition of the tyrosine kinase signaling
pathways associated with growth receptors [12]. The results
of our study were also worst than that reported for daily
oral selective epidermal growth factor receptor tyrosine
kinase inhibitors (EGFR-TKIs) therapy. In a phase II trial
of gefitinib in patients with advanced NSCLC who had
previously treated with a platinum-based therapy and
docetaxel, the response rate for the 102 evaluable patients
receiving 250 mg/day gefitinib was 11.8% and median
survival was 6.1 months [13]. In the trial was conducted
by the National Cancer Institute of Canada Clinical Trials
Group, erlotinib was compared with placebo for the treatment
of patients with locally advanced or metastatic NSCLC.
Approximately half of the patients were assigned to thirdline
treatment and the other half to second-line. In this
study, an improvement in survival was obtained in the
erlotinib arm; patients on placebo had a median survival
of 4.7 months whereas those on erlotinib had a median
survival of 6.7 months. The response rate to erlotinib was
8.9% [14]. Unfortunately, these EGFR-TKIs are not available
yet in our country.
Although the response rate, TTP and median survival
were disappointing, vinorelbine was well tolerated by the
patients. The main toxicity was myelosuppression. The
most common non-hematologic toxicities were asthenia,
nausea and neuropathy.
In conclusion, the administration of weekly vinorelbine
as a single agent has a favorable toxicity profile, but appears
has no relevant clinical activity in third-line chemotherapy
for patients with NSCLC. This regimen is not recommended
for third-line chemotherapy for patients pretreated with
platin- and taxanes-based combination chemotherapies.
Further evaluation of other salvage regimens seems to be
warranted.
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