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Phase II study of oral topotecan in advanced non-small cell lung cancer
S C White1, S Cheeseman, N Thatcher
1Department of Medical Oncology, Christie Hospital National Health Service Trust, Manchester, United Kingdom.
Abstract:
This study was designed to assess the activity of oral topotecan (TPT) in patients with advanced non-small cell lung cancer previously untreated with chemotherapy. Eligible patients had inoperable stage III or stage IV non-small cell lung cancer and were chemotherapy-naive. Other inclusion criteria were Eastern Cooperative Oncology Group performance status 0, 1, or 2, adequate bone marrow, and renal and hepatic function. Of 30 patients, 29 were assessable for response. Oral TPT was administered for 5 days every 21 days for up to six cycles unless disease progression or unacceptable toxicity occurred. Patients received a dose of 2.3 mg/m2/day for the first cycle. Dose modification for subsequent cycles was based on tolerability. Patients completed symptom questionnaires every 3 weeks. Pharmacokinetics were evaluated in all patients during cycle 1. Three patients had radiological responses with a reduction in tumor size of 30-40%. No patients achieved complete or partial responses to treatment. Thirteen patients had a stable disease (43.3%), and the median survival was 39.9 weeks with a 1-year survival of 33.3%. At the time of analysis, 27 patients had died. Median time to progression was 12.3 weeks. Treatment was well tolerated. A total of 125 cycles of treatment were completed. Twelve patients (40%) experienced grade III/IV neutropenia. Five patients (16.6%) had grade III/IV anemia. There were two episodes of grade III/IV thrombocytopenia. The main nonhematological toxicities consisted of grade III nausea (13%) and grade III vomiting (13%). The most frequently reported disease-related symptoms at baseline were dyspnea, cough, and fatigue. There was a subsequent improvement in patient scores of dyspnea in 17% of patients, 31% showed improvement in cough, and 32% showed improvement in fatigue. The mean area under the curve of TPT following 2.3 mg/m2 p.o. was 51.6 ng.h/ml (%SD, 25%). The area under the curve of TPT on day 1 of the first cycle was correlated with the percentage fall in leukocytes. Although oral TPT at the applied dose and schedule showed modest activity as a single agent, almost one-half of the patients had a stable disease, and median time to progression was 12.3 weeks. The overall median survival was a promising 39.9 weeks, and useful palliation of symptoms was seen.
Insights
Oral topotecan showed modest activity in advanced non-small cell lung cancer patients. The treatment resulted in stable disease for nearly half of patients and promising median survival, with symptom palliation observed.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Advanced non-small cell lung cancer (NSCLC) presents a significant therapeutic challenge, especially in chemotherapy-naive patients.
- Oral topotecan (TPT) is an established chemotherapeutic agent, but its efficacy as a single agent in advanced NSCLC warrants further investigation.
Purpose of the Study:
- To assess the clinical activity and tolerability of oral topotecan as a single agent in patients with advanced, chemotherapy-naive non-small cell lung cancer.
Main Methods:
- A phase II study enrolled 30 patients with inoperable stage III/IV NSCLC.
- Patients received oral TPT at 2.3 mg/m2/day for 5 days every 21 days, with dose adjustments based on tolerability.
- Tumor response, survival, time to progression, pharmacokinetics, and symptom burden were evaluated.
Main Results:
- Of 29 assessable patients, 43.3% achieved stable disease; no complete or partial responses were observed.
- Median survival was 39.9 weeks (1-year survival 33.3%), and median time to progression was 12.3 weeks.
- Treatment was generally well-tolerated, with manageable hematological (neutropenia, anemia) and non-hematological (nausea, vomiting) toxicities. Symptom improvements in dyspnea, cough, and fatigue were noted.
Conclusions:
- Oral topotecan demonstrated modest single-agent activity in advanced NSCLC, characterized by a notable proportion of stable disease and promising median survival.
- The drug was well-tolerated and provided useful palliation of key disease-related symptoms.
- Further research may explore combination strategies or specific patient subgroups for oral TPT in NSCLC treatment.