Phase II study of exatecan mesylate (DX-8951f) as first line therapy for advanced non-small cell lung cancer.

Abstract

BACKGROUND:

Exatecan mesylate (DX-8951f) is a water soluble analogue of camptothecin that inhibits topoisomerase I. This multi-centre phase II study evaluated the activity of single agent exatecan in previously untreated patients with advanced non-small cell lung cancer (NSCLC).

PATIENTS AND METHODS:

Patients with histologically or cytologically proven stage IIIb or IV NSCLC were treated with exatecan 0.5 mg/m(2) per day by 30 min intra-venous (i.v.) infusion for 5 days every 3 weeks to a maximum of six cycles. Measurable disease was documented prior to study entry and patients were re-staged every two cycles. Pharmacokinetic (PK) sampling was performed during cycle one.

RESULTS:

39 patients (32 patients ECOG performance status 0 or 1; 29 male and ten female; mean age 63 years) were entered into the study. Thirty-three completed at least two cycles of exatecan and 11 completed six cycles. Two patients (5.1%, 95% C.I. 0.3-21.3%) had a partial response, 7 (18.0%) minor response and 8 (20.5%) stable disease. Median time to tumour progression (TTP) was 88 days and median overall survival 262 days. The main toxicity was reversible neutropenia. PK analysis of exatecan demonstrated a mean clearance of 2.28 l/h per m(2), volume of distribution 18.2 l/m(2) and mean elimination half-life of 7.9 h.

CONCLUSIONS:

Exatecan mesylate has limited activity in advanced NSCLC and is not recommended for further evaluation as a single agent in this tumour type. PK data from this trial supports results established in phase I studies.

• Authors: J P Braybrooke, M Ranson, C Manegold, K Mattson, N Thatcher, P Cheverton, M Sekiguchi, M Suzuki, R Oyama, D C Talbot
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 41 Issue 2 Pg. 215-9 (Aug 2003) ISSN: 0169-5002 [Print] Ireland
• PMID: 12871785 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Antineoplastic Agents, Phytogenic
• exatecan
• Camptothecin

Topics

• Adult
• Aged
• Antineoplastic Agents, Phytogenic (administration & dosage, therapeutic use)
• Camptothecin (administration & dosage, analogs & derivatives, therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, mortality, secondary)
• Drug Administration Schedule
• Female
• Finland
• Germany
• Humans
• Infusions, Intravenous
• Japan
• Lung Neoplasms (drug therapy, mortality, pathology)
• Male
• Middle Aged
• Neoplasm Metastasis
• Neoplasm Staging
• Survival Analysis
• Treatment Outcome
• United Kingdom