Phase II study of oral topotecan in advanced non-small cell lung cancer

This study was designed to assess the activity of oral topotecan (TPT) in p atients with advanced non-small cell lung cancer previously untreated with chemotherapy, Eligible patients had inoperable stage III or stage TV non-sm all cell lung cancer and were chemotherapy-naive, Other inclusion criteria were Eastern Cooperative Oncology Group performance status 0, 1, or 2, adeq uate bone marrow, and renal and hepatic function. Of 30 patients, 29 were a ssessable for response. Oral TPT was administered for 5 days every 21 days for up to six cycles unless disease progression or unacceptable toxicity oc curred. Patients received a dose of 2.3 mg/m(2)/day for the first cycle, Do se modification for subsequent cycles was based on tolerability, Patients c ompleted symptom questionnaires every 3 weeks. Pharmacokinetics were evalua ted 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. T hirteen 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 pat ients had died. Median time to progression was 12.3 weeks. Treatment was well tolerated. A total of 125 cycles of treatment were compl eted. Twelve patients (40%) experienced grade III/IV neutropenia, Five pati ents (16.6%) had grade III/IV anemia. There were two episodes of grade III/ IV thrombocytopenia, The main nonhematological toxicities consisted of grad e III nausea (13%) and grade III vomiting (13%), The most frequently reported disease-related symptoms at baseline were dysp nea, cough, and fatigue. There was a subsequent improvement in patient scor es 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/m(2) p.o. was 51.6 ng .h/ml (%SD, 25%), The area under the curve of TPT on day 1 of the first cyc le was correlated with the percentage fall in leukocytes, Although oral TPT at the applied dose and schedule showed modest activity a s 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.