Phase II study of oral topotecan in advanced non-small cell lung cancer.
AuthorsWhite, Shane C
Carrington, Bernadette M
Ross, Graham A
Ranson, Malcolm R
AffiliationDepartment of Medical Oncology, Christie Hospital National Health Service Trust, Manchester, United Kingdom.
MetadataShow full item record
AbstractThis 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.
CitationPhase II study of oral topotecan in advanced non-small cell lung cancer. 2000, 6 (3):868-73 Clin. Cancer Res.
JournalClinical Cancer Research
- Oral topotecan given once or twice daily for ten days: a phase I pharmacology study in adult patients with solid tumors.
- Authors: Gerrits CJ, Burris H, Schellens JH, Eckardt JR, Planting AS, van der Burg ME, Rodriguez GI, Loos WJ, van Beurden V, Hudson I, Fields S, Von Hoff DD, Verweij J
- Issue date: 1998 May
- Phase I and pharmacologic study of sequential topotecan-carboplatin-etoposide in patients with extensive stage small cell lung cancer.
- Authors: Miller AA, Al Omari A, Murry DJ, Case D
- Issue date: 2006 Dec
- Topotecan plus ifosfamide in patients with platinum refractory advanced/metastatic non-small cell lung cancer: a phase II trial.
- Authors: Lorusso V, Gebbia V, Spada M, Guida M, Cassano G, Brunetti C, Germano D, Nettis G, Izzi G, Galetta D, Giampaglia M, Silvestris N, Colucci G
- Issue date: 2005 Dec
- Paclitaxel and carboplatin in inoperable non-small cell lung cancer.
- Authors: Kosmidis P, Mylonakis N, Fountzilas G, Samantas E, Athanasiadis A, Skarlos D
- Issue date: 1996 Dec
- European organization for research and treatment of cancer (EORTC) 08957 phase II study of topotecan in combination with cisplatin as second-line treatment of refractory and sensitive small cell lung cancer.
- Authors: Ardizzoni A, Manegold C, Debruyne C, Gaafar R, Buchholz E, Smit EF, Lianes P, ten Velde G, Bosquee L, Legrand C, Neumaier C, King K, Giuseppe giaccone European organization for research and treatment of cancer (EORTC) lung cancer group.
- Issue date: 2003 Jan