A randomized phase III trial of four chemotherapy regimens in advanced non-small cell lung cancer (NSCLC)
Theodore Robnett, MD
OncoLink Assistant Editor
Last Modified: May 22, 2000
Presenter: Joan H. Schulter
Since the initial randomized trials in the early
1990's which showed improved median and overall
survival by adding chemotherapy to radiation
therapy (RT) in NSCLC patients, several newer
agents have been introduced. Some of these
agents are used off protocol based on phase II
data, known activity in other sites, and results
of small phase III trials. This trial tests
3 "experimental" chemotherapy arms against a
single "reference" arm.
Materials and Methods:
- All arms contained either cisplatin (P), or
carboplatin (Cb). Arm A, the reference arm, used
P + paclitaxel (T). Arm B used Gemcitabine (G)
and P. Arm C used docetaxel (Tx) and P. Arm D
used T and Cb.
- Dosages were: arm A - P 75 mg/m2 on day 1, T
175 mg/m2/24 hours; arm B - G 1000 mg/m2 on days
1, 8, 15 and P 100 mg/m2 on day 1; arm C - Tx
and P both 75 mg/m2 on day 1; arm D - T 225
mg/m2/3 hours on day 1 and Cb AUC of 6 on day 1.
- Arms A,C, and D repeated q21 days, arm D q28
- Eligible patients were required to have
measurable or evaluable disease, ECOG performance
status (PS) of 0-2 (changed to 0-1 in 10/97 due
to excess toxicity), stage IIIB (because of
malignant pleural or pericardial effusion) or
stage IV disease. Patients were stratified by
brain metastasis, weight loss, and age.
- Patients were registered between 10/96 and 5/99.
- 1207 patients were registered on study, 1146
were eligible for analysis. Of the eligible
patients, 1083 had performance status (PS) 0-1,
and 968 were stage IV. 994 patients had died as
of May 1, 2000.
- Median follow-up was 7.7 months. Median
survival was 7.8 months.
- In general, the four arms were found to have
comparable toxicities. Less fever and
neutropenia was seen in arms B and C. Less
nausea and fewer grade 4-5 toxicities were seen
in arm D, but patients in arm D experienced worse
- Median survival in arms A, B, C, and D were 7.1
months, 8.1 months, 7.4 months, 8.2 months,
respectively. One year actuarial survival for
these arms was 31%, 36%, 31%, and 34%,
respectively. Overall response was 21%, 21%,
17%, and 15%, respectively. None of these
differences were statistically significant. An
increased time to progression was seen in arm B.
None of these data were available at the time the
abstract was printed.
- Among these four treatment modalities, there
was no difference in overall survival between
arms. Treatment with the gemcytabine arm showed
a statistically significant increase in time to
- The chemotherapy regimens offer a modest but
significant improvement over observation alone.
The pursuit of more effective treatment for
locally advanced NSCLC continues. Currently, cure
rates are low and there is little hope in the
near future for improvement. Although there have
been increased response rates using newer drugs
as single agents, combination chemotherapy does
not appear to yield significant gains.