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Phase II study of topotecan in metastatic non-small-cell lung cancer
Purpose:
Topotecan is an inhibitor of topoisomerase I that has shown preclinical activity against non-small-cell lung cancer (NSCLC). This phase II study was designed to determine the clinical activity and toxicity spectrum of topotecan in untreated patients with metastatic NSCLC.
Patients And Methods:
Twenty previously untreated patients received topotecan every 21 days at the dose of 2 mg/m2/d intravenously (IV) for 5 days for two cycles, at which point response was assessed. Patients with either clinical response or stable disease (SD) received additional cycles of the drug until toxicity developed or disease progression (PRG) occurred.
Results:
This study was designed to enter 30 patients. However, because no clinical responses were seen in the first 20 patients entered onto the study, the early-stopping rule was invoked and patient accrual was halted. Eleven patients (55%) had SD on topotecan, and nine (45%) had PRG. Toxicity included neutropenia and rash. The median survival duration for all patients was 7.6 months.
Conclusion:
We observed no objective clinical responses despite producing high-grade neutropenia. Phase II trials of topotecan using different schedules or higher doses supported by growth factors may clarify the role of topotecan in the treatment of NSCLC. The combination of topotecan with cisplatin and topoisomerase II inhibitors such as etoposide should be explored. Finally, the median survival duration of 7.6 months for 20 patients treated with an agent that failed to produce any obvious clinical responses compares favorably to the survival obtained with combinations of existing agents. This supports the further study of novel compounds in this clinical setting.
Insights
Topotecan showed no objective clinical responses in patients with metastatic non-small-cell lung cancer (NSCLC), despite causing neutropenia. Further studies with different schedules or combinations are recommended for this NSCLC treatment.
Area of Science:
- Oncology
- Pharmacology
Background:
- Topotecan, a topoisomerase I inhibitor, demonstrated preclinical activity against non-small-cell lung cancer (NSCLC).
- This study evaluated topotecan's efficacy and safety in previously untreated metastatic NSCLC patients.
Purpose of the Study:
- To determine the clinical activity and toxicity of topotecan in untreated patients with metastatic NSCLC.
Main Methods:
- A phase II study involving 20 previously untreated patients with metastatic NSCLC.
- Topotecan administered intravenously at 2 mg/m2/d for 5 days every 21 days for two cycles.
- Patients with stable disease or clinical response received additional cycles until toxicity or progression.
Main Results:
- The study was halted early due to lack of objective clinical responses in the first 20 patients.
- Eleven patients (55%) had stable disease (SD), and nine (45%) experienced disease progression (PRG).
- Observed toxicities included neutropenia and rash, with a median survival of 7.6 months.
Conclusions:
- Topotecan did not produce objective clinical responses in this patient group, despite causing high-grade neutropenia.
- Further research with alternative topotecan schedules, higher doses, growth factors, or combination therapies (e.g., with cisplatin, etoposide) is warranted.
- The median survival suggests potential for novel agents in NSCLC treatment, supporting further investigation.