Literature DB >> 23391616

Efficacy and safety of oral topotecan and bevacizumab combination as second-line treatment for relapsed small-cell lung cancer: an open-label multicenter single-arm phase II study.

David R Spigel1, David M Waterhouse, Steve Lane, Philippe Legenne, Kamal Bhatt.   

Abstract

BACKGROUND: Topotecan is currently the only US Federal Drug Administration (FDA)-approved drug for second-line treatment of relapsed small-cell lung cancer (SCLC). We investigated the efficacy and safety of a novel topotecan-bevacizumab combination in treating relapsed SCLC. PATIENTS AND METHODS: Each 21-day treatment cycle consisted of bevacizumab (15 mg/kg) administration on day 1 and oral topotecan (2.3 mg/m(2)/d) administration on days 1 to 5. Treatment was continued for 8 cycles or until disease progression/toxicity. The primary objective was evaluation of 3-month progression-free survival (PFS). Overall response rate (ORR), duration of response, time to response (TTR), and overall survival (OS) were secondary objectives.
RESULTS: The study enrolled 50 patients between July 2008 and May 2010. The 3-month PFS was 65% (95% confidence interval [CI], 49.3%-76.9%), which was promising compared with the historical control of 50% (P = .017) but did not meet the predefined criteria for clinically meaningful improvement. Median PFS was 6.24 months for the sensitive subgroup (progression time from end of previous chemotherapy > 90 days; n = 27) and 2.91 months for the resistant subgroup (progression time ≤ 90 days; n = 23). No patient achieved complete response (CR), and the ORR was 16%. Twenty (40%) patients had stable disease (SD) and 13 (26%) had progressive disease (PD). Median OS, TTR, and duration of response were 7.4, 1.3, and 4.7 months, respectively. The worst reported adverse events (AEs) were grade 1/2 in 11 (22%) patients and grade 3/4/5 in 39 (78%) patients.
CONCLUSION: Improvement in the 3-month PFS after treatment with topotecan-bevacizumab was promising compared with the historical control and justifies additional studies with this regimen.
Copyright © 2013. Published by Elsevier Inc.

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Year:  2013        PMID: 23391616     DOI: 10.1016/j.cllc.2012.12.003

Source DB:  PubMed          Journal:  Clin Lung Cancer        ISSN: 1525-7304            Impact factor:   4.785


  17 in total

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Journal:  Transl Lung Cancer Res       Date:  2016-02

2.  FL118, a novel camptothecin analogue, overcomes irinotecan and topotecan resistance in human tumor xenograft models.

Authors:  Xiang Ling; Xiaojun Liu; Kai Zhong; Nicholas Smith; Joshua Prey; Fengzhi Li
Journal:  Am J Transl Res       Date:  2015-10-15       Impact factor: 4.060

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Journal:  Med Oncol       Date:  2017-04-29       Impact factor: 3.064

4.  Pharmacodynamics and pharmacokinetics of oral topotecan in patients with advanced solid tumours and impaired renal function.

Authors:  Lot A Devriese; Petronella Els O Witteveen; Marja Mergui-Roelvink; Deborah A Smith; Lionel D Lewis; David S Mendelson; Yung-Jue Bang; Hyun Choel Chung; Mohammed M Dar; Alwin D R Huitema; Jos H Beijnen; Emile E Voest; Jan H M Schellens
Journal:  Br J Clin Pharmacol       Date:  2015-05-20       Impact factor: 4.335

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Journal:  Signal Transduct Target Ther       Date:  2022-06-15

6.  Combination therapy with topotecan, paclitaxel, and bevacizumab improves progression-free survival in recurrent small cell neuroendocrine carcinoma of the cervix.

Authors:  M Frumovitz; M F Munsell; J K Burzawa; L A Byers; P Ramalingam; J Brown; R L Coleman
Journal:  Gynecol Oncol       Date:  2016-11-04       Impact factor: 5.482

Review 7.  Targeting angiogenesis in small cell lung cancer.

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Journal:  Transl Lung Cancer Res       Date:  2016-08

Review 8.  Origins, genetic landscape, and emerging therapies of small cell lung cancer.

Authors:  Ekaterina A Semenova; Remco Nagel; Anton Berns
Journal:  Genes Dev       Date:  2015-07-15       Impact factor: 11.361

Review 9.  Advances in antiangiogenic treatment of small-cell lung cancer.

Authors:  Hongyang Lu; Zhiming Jiang
Journal:  Onco Targets Ther       Date:  2017-01-12       Impact factor: 4.147

10.  Meta-analysis of the role of bevacizumab in extensive stage small cell lung cancer.

Authors:  Yan-Juan Zhu; Hai-Bo Zhang; Yi-Hong Liu; Jian-Ping Bai; Yong Li; Li-Rong Liu; Yan-Chun Qu; Xin Qu; Xian Chen
Journal:  Oncol Lett       Date:  2017-05-25       Impact factor: 2.967

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