A new study presented at the Ninth World Congress
on Lung Cancer demonstrated that topotecan (Hycamtin) in combination with carboplatin (Paraplatin) is active as a first-line
treatment of advanced non-small-cell lung cancer. Topotecan is not currently
approved for the treatment of patients with non-small-cell lung cancer.
The noncomparative, multicenter study, conducted by L’Hopital
Arnaud de Villeneuve, in conjunction with SmithKline Beecham, evaluated the
activity of topotecan in combination with carboplatin in chemotherapy-naive
patients. Results from the investigation indicate that the combination produced
an overall response rate of 14% in evaluable patients, with 49% achieving an
arrest in tumor progression.
"These results indicate that topotecan is active in solid
tumors other than ovarian and small-cell lung cancer," said Jean-Louis
Pujol, MD, L’Hôpital Arnaud de Villeneuve, Montpellier, France. "They
also underscore the fact that combination treatment with topotecan may offer
patients with non-small-cell lung cancer an additional therapeutic
Activity of Topotecan
In this phase II trial, 47 chemotherapy-naive, non-small-cell
lung cancer patients were treated with IV topotecan 0.5 mg/m2 daily for 5 days,
with an area under the concentration-time curve (AUC) 5 dose of carboplatin
administered on the first day of treatment. The regimen was repeated every 21
days. Patients received a median of four courses of treatment; reductions and
escalations in the dose of topotecan were based on the incidence of toxicity
and/or adverse events.
Of the 42 patients who were evaluable for efficacy, 14% achieved
an objective response (one complete response, five partial responses). Stable
disease that lasted at least 56 days was reported in 36% of patients (n = 17).
When the overall response and stable disease rates were combined, 49% of
patients achieved an arrest in tumor progression. The median duration of
response was 16 weeks, with a median survival of 32.7 weeks.
"The study results are interesting in light of the Eastern
Cooperative Oncology Group (ECOG) 1594 study comparing three front-line non-small-cell
lung cancer regimens to the standard of care that was presented at ASCO
[American Society of Clinical Oncology] this spring , where the median
survival across the four regimens ranged from 31 to 36 weeks," said Dr.
Hematologic toxicities were the most frequent adverse events,
but were reversible in most patients. The most common hematologic events
included grade 3/4 anemia in 36% of patients, neutropenia in 53%, and
thrombocytopenia in 58%. Nonhematologic events included asthenia in 11% of
patients, dyspnea in 6%, and infection in 6%. These toxicities were mild or
moderate in severity and manageable with the usual methods of supportive care.
Additional presentations at the Ninth World Congress on Lung
Cancer included a phase I/II study that evaluated the activity of oral topotecan
in combination with either paclitaxel (Taxol) or cisplatin (Platinol) in the
treatment of chemotherapy-naive patients with non-small-cell lung cancer.
According to data from the phase I trial, oral topotecan in combination with
paclitaxel produced an overall response rate of 12% (n = 33) in patients who
were evaluable for response. Further, 27% of the treated patients achieved
stable disease lasting at least 56 days.
The investigators noted that it was premature to evaluate
survival. Grade 3 and 4 hematologic toxicities included neutropenia and anemia,
which were reported in 68% and 18% of patients, respectively. The most frequent
grade 3 and 4 nonhematologic toxicities included dyspnea (17%), nausea (12%),
and vomiting (12%) at the maximum tolerated dose.
Phase II Study
In the phase II study of 50 patients, 28% (n = 14) of those
treated with oral topotecan and cisplatin achieved a partial response, while 16%
(n = 8) experienced disease stabilization that lasted more than 56 days. In this
study, the median survival was 35.4 weeks. The most common adverse events
included grade 3/4 neutropenia, anemia, and thrombocytopenia in 70%, 48%, and
46% of patients, respectively. All of the nonhematologic toxicities were mild or
moderate and manageable and included vomiting (27%), anorexia (20%), and
"These data illustrate that oral topotecan in combination
with paclitaxel or cisplatin produces activity with acceptable tolerability and
an acceptable androgen-receptor profile," said Professor Torben Palshof,
MD, Arhus Kommunehospital, Copenhagen, Denmark. "These results, together
with those of the topotecan and carboplatin study, indicate that topotecan has
the potential to provide patients with an additional therapeutic option.
Further, the 56-day sustained disease stabilization observed in these trials
bodes well for the use of topotecan in this treatment population."
Studies assessing the safety and efficacy of oral topotecan in
various tumor types are currently ongoing.