Topotecan (T) vs. Observation (OB) Following Cisplatin (P) Plus Etoposide (E) in Extensive Stage Small Cell Lung Cancer (ES SCLC) (E7593): A Phase III Trial of the Eastern Cooperative Oncology Group (ECOG)
Diana Stripp, MD
OncoLink Assistant Editor
Ultima Vez Modificado: 22 de mayo del 2000
Presenter: D. H. Johnson Affiliation: Vanderbilt University
Background: Topotecan, a topoisomerase I inhibitor, has a 40%
response rate as a first line agent in SCLC and
moderate activity in chemoresistant SCLC. This
Phase III trial was designed to determine
Topotecan?s efficacy in combination with standard
Materials and Methods:
Eligibility: patients with histologically
confirmed SCLC, extensive stage, no previous
treatment, no prior malignancy, performance
status 0-2, age ³ 18y.o., normal organ function,
stable brain metastases were allowed.
All pts received 4 cycles of P (60mg/m2 IV, D1)
and E (120mg/m2 IV, D 1-3) q3 wks. Pts with
stable or responding disease were then randomized
- Observation (Ob)
- 4 cycles of T (1.5mg/m2/dx5days, q3wk).
402 eligible pts were registered to Step 1 and
242 eligible pts to Step 2 (Ob 120 and T 122).
The 2 groups were well balanced for demographic
characteristics, usual prognostic factors.
The CR and PR rates to induction PE were 3% and
With T, an additional 2% CR and 5% PR were
Median survival for all 402 eligible pts was
Progression Free Survival (PFS) from date of
Step 2 randomization was significantly better for
T compared to Ob (3.6 vs. 2.6 mos, p= 0.0001).
However, there were no significant differences
between the 2 groups in overall survival, median
survival (T 9.3mos and Ob 8.9) or 1-yr survival
(T 27% and Ob 25%).
Toxicity: Grade 4 neutropenia and
thrombocytopenia occurred in 50% and 3%
respectively in Step 1 and 58% and 12% of T pts
in Step 2. Grade 3-5 infection was observed in
8% Step 1 pts and 4.5% T pts in Step 2. Grade 3-4
anemia developed in 21% of pts receiving T.
Quality of Life data analysis showed no
differences in pts who received T vs. those on Ob.
4 cycles of PE induction therapy followed by 4
cycles of T improved PFS but failed to improve
overall survival in ES SCLC.
T did not improve QOL and was associated with
4 cycles of standard PE remains an appropriate
first-line treatment for good performance status
extensive stage SCLC pts.
Though topotecan has modest activity as a first
line or 2nd line agent in SCLC, topotecan
following standard PE chemotherapy not only did
not improve overall survival or quality of life
but also was associated with increased
Dec 19, 2014 - In a phase III clinical trial, gefitinib was superior to carboplatin-paclitaxel in extending survival for patients with non-small-cell lung cancer, particularly those patients with epidermal growth factor receptor gene mutations, according to a study published online Aug. 19 in the New England Journal of Medicine.