Open-Label, Multicenter, Randomized, Phase III Study Comparing Oral Topotecan/Cisplatin Versus Etoposide/Cisplatin As Treatment for Chemotherapy-Naive Patients With Extensive-Disease Small-Cell Lung Cancer

Eckardt, John R.; Pawel, Joachim von; Papai, Z.; Tomova, Antoaneta; Tzekova, Valentina; Crofts, T.; Brannon, Sarah; Wissel, Paul; Ross, Graham

doi:10.1200/jco.2005.03.3332

Cited by 134 publications

(102 citation statements)

References 16 publications

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“…On the other hand, given the high single-agent activity of belotecan against SCLC (17), a regimen with a higher dose of belotecan and a lower dose of cisplatin seemed likely to be more effective. In addition, recently conducted trials used 60 mg/m 2 cisplatin for the combination of irinotecan or topotecan (8,11,12,19).…”

Section: Discussionmentioning

confidence: 99%

“…Belotecan , which had been chosen in the trials of irinotecan or topotecan-cisplatin combination (8,11,12,18,19). DLT was determined during the first cycle only and defined as follows: grade 4 neutropenia (absolute neutrophil count <500/mm 3 ) lasting 7 days; grade 4 neutropenia with fever (V38.5jC) or sepsis; grade 4 thrombocytopenia (platelet <10,000/mm 3 ); and grade 3 or 4 nonhematologic toxicity other than nausea, vomiting, and alopecia.…”

Section: Methodsmentioning

confidence: 99%

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A Phase I and Pharmacologic Study of Belotecan in Combination with Cisplatin in Patients with Previously Untreated Extensive-Stage Disease Small Cell Lung Cancer

Lee

Bae²,

Hong³

et al. 2007

Clinical Cancer Research

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Purpose: Belotecan (Camtobell, CKD602) is a novel camptothecin derivative. This study was designed to determine the maximum tolerated dose (MTD), toxicity profile, and doselimiting toxicity of belotecan in combination with cisplatin in patients with previously untreated extensive-stage disease small cell lung cancer (SCLC). Furthermore, pharmacokinetics and preliminary antitumor activity against SCLC were evaluated. Combination chemotherapy remains the main treatment of patients with extensive-stage disease small cell lung cancer (SCLC). Etoposide and cisplatin combination has been used as a standard treatment. However, although initial response rates to etoposide-cisplatin combination were up to 80%, the median survival time of patients treated with etoposide-cisplatin regimen was reportedly only 8 to 9 months and 2-year survival of 4% (1 -4). Several new drugs, such as paclitaxel, topotecan, and irinotecan, were shown to be active in chemotherapy-naive or chemosensitive patients with SCLC, in which the response rates had reached 40% (5 -7). However, except the Japanese trial (8), new regimens containing these new drugs failed to show the survival benefit compared with the standard etoposide-cisplatin regimen (9 -11). Irinotecan and cisplatin regimen showed survival advantage in Japan (8), but a subsequent trial in Western countries failed to confirm the survival benefit of this regimen over etoposide-cisplatin regimen (12). Belotecan [Camtobell, CKD602,ethyl]-(20S)-camptothecin, Chong Keun Dang Corp.] is a novel camptothecin derivative, in which a water-solubilizing group is introduced at position of the B ring (13). The preclinical studies showed that belotecan was a more potent topoisomerase I inhibitor in the cleavable complex assay and had superior in vitro and in vivo antitumor activity to camptothecin and topotecan in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell cytotoxicity assay and six human tumor xenografts (13,14). Of interest, the mean ATI values of belotecan were over 2-fold higher than those of topotecan, suggesting that this drug would show encouraging antitumor activity in a clinical study. Although several in vitro and in vivo test systems developed to predicting the clinical activity have some limitations, the ATI values, defined as the area under the inhibition ratio (%) versus time curve plotted from 0 to 240 min as obtained by ex vivo pharmacodynamic assay and calculated by trapezoidal rule, showed a good clinical correlation with the clinical response (15). In a phase I study, the maximum tolerated dose (MTD) of single-agent belotecan was 0.7 mg/m 2 /d when given i.v. daily for 5 consecutive days every 3 weeks and the dose-limiting toxicity

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

A Phase I and Pharmacologic Study of Belotecan in Combination with Cisplatin in Patients with Previously Untreated Extensive-Stage Disease Small Cell Lung Cancer

Lee

Bae²,

Hong³

et al. 2007

Clinical Cancer Research

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“…The doublet oral topotecan plus cisplatin (TC) showed both similar benefit and toxicity to EP. Grades 3 and 4 neutropaenia were more frequent with EP (84% vs 59%), whereas TC caused a higher rate of anaemia (38% vs 21%), thrombocytopaenia (38% vs 23%) and diarrhoea (33% vs 18%), but a lower rate of alopecia (TC 24% vs PE 40%) (Eckardt et al, 2006;Heigener et al, 2008).…”

Section: Treatment Of Edmentioning

confidence: 94%

Treatment options for small cell lung cancer – do we have more choice?

et al. 2010

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“…Phase II and III studies have been conducted with oral topotecan in the first-and second-line treatment of SCLC (Table 2) [10,[37][38][39][40]. Of particular note are two recent randomized phase III trials that demonstrate the activity of oral topotecan both in a combination regimen as first-line treatment and as monotherapy in the second-line treatment of patients with SCLC [10,40].…”

Section: Oral Topotecan In Sclcmentioning

confidence: 99%

Recent Advances with Topotecan in the Treatment of Lung Cancer

O’Brien

Eckardt²,

Ramlau

2007

The Oncologist

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After completing this course, the reader will be able to:1. Describe phase I studies evaluating the pharmacokinetics and early safety data of single-agent oral topotecan. Discuss the results and implications of clinical trials evaluating oral topotecan for small cell lung cancer (SCLC)and non-small cell lung cancer (NSCLC).3. Explain why topotecan is a good candidate for combination with other novel anticancer agents.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME Further, an oral formulation of topotecan is currently under investigation and may provide added convenience for patients. Oral topotecan has been studied in the first-and second-line settings for both SCLC and non-small cell lung cancer (NSCLC). Three recent phase III trials have demonstrated the activity of oral topotecan. In the first study of chemotherapy-naïve patients with extensivedisease SCLC, oral topotecan plus cisplatin provided efficacy and safety similar to those of etoposide plus cisplatin. In a second study of patients with relapsed SCLC, treatment with oral topotecan showed a statistically significant and clinically meaningful longer overall survival time and improvement in dyspnea and quality of life compared with best supportive care alone in all prognostic groups. Finally, in previously treated patients with NSCLC, single-agent oral topotecan was shown to be noninferior in 1-year survival rate relative to the current standard of i.v. docetaxel. In future studies, oral topotecan will represent a good candidate for combination therapy with other i.v. or oral chemotherapy agents, monoclonal antibodies, and small molecule tyrosine kinase inhibitors. ABSTRACT

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Open-Label, Multicenter, Randomized, Phase III Study Comparing Oral Topotecan/Cisplatin Versus Etoposide/Cisplatin As Treatment for Chemotherapy-Naive Patients With Extensive-Disease Small-Cell Lung Cancer

Abstract: Oral topotecan with cisplatin provides similar efficacy and tolerability to the standard (etoposide with cisplatin) in untreated ED-SCLC and may provide greater patient convenience compared with intravenous etoposide and cisplatin.

Cited by 134 publications

References 16 publications

A Phase I and Pharmacologic Study of Belotecan in Combination with Cisplatin in Patients with Previously Untreated Extensive-Stage Disease Small Cell Lung Cancer

A Phase I and Pharmacologic Study of Belotecan in Combination with Cisplatin in Patients with Previously Untreated Extensive-Stage Disease Small Cell Lung Cancer

Treatment options for small cell lung cancer – do we have more choice?

Recent Advances with Topotecan in the Treatment of Lung Cancer

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