HOUSTONImproved survival with a very favorable toxicity profile
resulted from using weekly single-agent paclitaxel (Taxol) 80
mg/m² in patients with advanced nonsmall-cell lung cancer
(NSCLC) who failed first-line therapy with paclitaxel/carboplatin
This was among the findings of a multi-institutional study evaluating
ways to extend the efficacy of paclitaxel while minimizing toxicity.
Merrill Kies, MD, of M.D. Anderson Cancer Center, presented the study
at the ASCO meeting.
Coinvestigator Mark Socinski, MD, of the University of North
Carolina, Chapel Hill, commented, This regimen has notable
median and 1-year survival rates with substantially less toxicity
than other single agents in this setting.
All patients were included in a phase III trial to determine the
optimal duration of first-line paclitaxel/carboplatin. They were then
divided into three groups. Group 1 included refractory patients who
progressed after two cycles of first-line chemotherapy. Group 2
received four cycles of first-line chemotherapy and were followed
until disease progression. Group 3 received continuous
paclitaxel/carboplatin until progression.
The overall response rate to first-line chemotherapy was 26.6%.
Patients then received second-line weekly paclitaxel after disease
progression, for a median of 8 weekly treatments. Median survival
from the start of second-line therapy was 5.9 months for all 44
assessable patients, with no differences seen among the groups.
Second-line weekly paclitaxel produced an overall response rate of
6.8%. Stable disease was demonstrated in 38.6% of patients at 8
weeks, Dr. Kies reported.
Virtually all responses occurred in patients who had received four
cycles of first-line chemotherapy and were taken off treatment for 4
months before starting weekly paclitaxel. Responses to second-line
paclitaxel were not noted in patients who progressed after two cycles
of continuous first-line treatment.
While this was not a randomized prospective trial, Dr. Kies
highlighted the good response in patients who had interrupted
treatment, which he said is consistent with the emerging concept that
responses are more likely after a treatment-free interval.
A median survival of almost 11 months was noted for the entire group.
One-year survival was 39%, and 2-year survival was 23%. Median
survival duration by subgroup was 6.3 months for group 1, 12.5 months
for group 2, and 11.7 months for group 3. Median 1-year survival by
group was 12% for group 1, 54% for group 2, and 45% for group 3, Dr.
Grade 2-3 neuropathy occurred in seven patients. Three patients
developed grade 3 neuropathy on weekly therapy. There were no grade 4
toxicities and no differences in quality of life among the 26
patients assessed for this.
The overall survival looks promising in the early returns,
Dr. Kies commented. If the encouraging survival holds up, he said
the study would generate a lot of interest.