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)
Presenter: D. H. Johnson
Affiliation: Vanderbilt University
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 chemotherapy.
- 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 to: - 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 32%.
- With T, an additional 2% CR and 5% PR were achieved.
- Median survival for all 402 eligible pts was 9.6 mos.
- 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 increased toxicity.
- 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 toxicity profile.