Phase II study of topotecan in patients with advanced non-small-cell lung cancer previously untreated with chemotherapy

Author(s): Perez-Soler R, Fossella FV, Glisson BS, Lee JS, Murphy WK, et al.


Purpose: This study was designed to assess the anti-tumor activity of topotecan (TPT) in patients with advanced non-small-cell lung cancer (NSCLC) previously untreated with chemotherapy.

Patients and methods: Patients with stage IIIB or IV NSCLC with measurable disease in nonradiated fields were eligible. Other eligibility criteria were Zubrod performance status (PS) < or = 2 and adequate renal and liver function. TPT was administered at a dose of 1.5 mg/m2/d for 5 days over 30 minutes every 21 days. Of 48 registered patients, 40 were fully assessable. Nineteen patients had adenocarcinoma (AD), 14 squamous carcinoma (SCC), and seven poorly differentiated carcinoma.

Results: Six patients (15%) achieved a partial remission (PR) (durations: 8, 14, 18, 28, 56, and 61 weeks) and four patients a minor response; 10 patients had stable disease and 20 patients progressive disease. The PR rate was 36% (five of 14 patients) in patients with SCC versus 4% (one of 26 patients) in those with other histologies (P = .014). The overall median survival time was 38 weeks and 30% of patients were alive at 1 year. Grade 3 to 4 granulocytopenia and thrombocytopenia occurred after 76% and 10% of courses administered, respectively. No grade 3 to 4 nonhematologic toxicities were observed. Grade 1 or 2 nonhematologic toxicities consisted of nausea (46% and 5%), vomiting (31% and 7%), and fatigue (53% and 16%).

Conclusion: TPT at the dose and schedule used has moderate antitumor activity in NSCLC; its activity is mostly limited to patients with SCC. TPT is well tolerated, with myelosuppression of short duration being the most common and limiting toxicity.

Similar Articles

Medicinal plants and phytomedicines

Author(s): Briskin DP

New natural products as new leads for antibacterial drug discovery

Author(s): Brown DG, T Lister, TL May-Dracka

Amazonian plant natural products: perspectives for discovery of new antimalarial drug leads

Author(s): Pohlit AM, Souza Lima RB,Frausin G,Rocha e SilvaLF,Pinto Lopes SC, et al.

Natural products: promising resources for cancer drug discovery

Author(s): Mondal S, Bandyopadhyay S, Ghosh MK, Mukhopadhyay S, Roy S, et al.

Plant antitumor agents

Author(s): Wall ME, MC Wani, CE Cook, KH Palmer, AT McPhail, et al.

Plant antitumor agents

Author(s): Wani MC, Taylor HL, WallME, Coggon P, McPhail AT, et al.

3D-QSAR study of 20 (S)-camptothecin analogs

Author(s): Lu AJ, Zhang ZS, Zheng MY, Zou HJ, Luo XM, et al.

Plants used against cancer

Author(s): Hartwell JL

Plants used against cancer

Author(s): Hartwell JL

Screening plants for antitumor activity

Author(s): Perdue RE Jr, Abbott BJ, Hartwell JL

Antineoplastic components of marine animals

Author(s): Pettit GR, Day JF, Hartwell JL, Wood HB

Studies on Camptothecin

Author(s): Horwitz SB, Chang CK, Grollman AP

Grollman, Antiviral action of camptothecin

Author(s): Horwitz SB, Chang CK, Grollman AP

DNA topoisomerase I-mediated DNA cleavage and cytotoxicity of camptothecin analogues

Author(s): Hsiang YH, Liu LF, Wall ME, Wani MC, Nicholas AW

Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA

Author(s): Redinbo MR, Stewart L, Kuhn P, Champoux JJ, Hol WG

Mechanism of action of camptothecin

Author(s): Liu LF, Desai SD, Li TK, Mao Y, Sun M, et al.

Antitumour drugs impede DNA uncoiling by topoisomerase I

Author(s): Koster DA, Palle K, Bot ES, Bjornsti MA, Dekker NH

Phase I and pharmacologic study of topotecan: a novel topoisomerase I inhibitor

Author(s): Rowinsky EK, Grochow LB, Hendricks CB, Ettinger DS, Forastiere AA, et al.

Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer

Author(s): ten Bokkel Huinink W, Gore M, Carmichael J, Gordon A, Malfetano J, et al.

Phase I clinical trial of topotecan and pegylated liposomal doxorubicin

Author(s): Garcia AA, Roman L, Muderspach L, O'meara A, Facio G, et al.

Preclinical evaluation of the anticancer activity and toxicity of 9-nitro-20(S)-camptothecin (Rubitecan)

Author(s): Giovanella BC, Stehlin JS, Hinz HR, Kozielski AJ, Harris NJ, etal.

A phase II trial with RFS2000 (rubitecan) in patients with advanced non-small cell lung cancer

Author(s): Baka S, Ranson M, Lorigan P, Danson S, Linton K, et al.

Phase II trial of oral rubitecan in previously treated pancreatic cancer patients

Author(s): Burris HA, Rivkin S, Reynolds R, Harris J, Wax A, et al.

Anti-apoptotic mechanisms of drug resistance in cancer

Author(s): Wilson TR, Johnston PG, Longley DB