Marjorie G Zauderer1, Samantha L Kass2, Kaitlin Woo3, Camelia S Sima3, Michelle S Ginsberg4, Lee M Krug5. 1. Department of Medicine, Division of Solid Tumor Oncology, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, United States. Electronic address: zauderem@mskcc.org. 2. Georgetown University School of Medicine, United States. 3. Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, United States. 4. Department of Radiology, Memorial Sloan Kettering Cancer Center, United States. 5. Department of Medicine, Division of Solid Tumor Oncology, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, United States.
Abstract
OBJECTIVES: Pemetrexed-cisplatin is the only FDA-approved regimen for malignant pleural mesothelioma (MPM), and the impact on survival is modest. No drugs have been shown to improve survival as second-line therapy, yet vinorelbine and gemcitabine are prescribed based on the results of small phase II trials. To augment the existing limited data, we examined our institutional experience with vinorelbine and gemcitabine in patients with previously treated MPM. MATERIALS AND METHODS: We reviewed charts of patients with MPM treated with vinorelbine and/or gemcitabine as second- or third-line therapy between 2003 and 2010. Toxicity was graded according to the Common Terminology Criteria for Adverse Events Version 4.0. CT scans were reviewed with a reference radiologist according to modified RECIST criteria. RESULTS: Sixty patients were identified: 33 treated with vinorelbine, 15 gemcitabine, and 12 both agents. Eighty-three percent initially received pemetrexed-platinum. Toxicity was substantial: 46% experienced at least one episode of grade 3-4 toxicity. Of 56 patients evaluable radiologically, there was 1 partial response (gemcitabine) giving a response rate of 2% (95% CI: 0-10%). Forty-six percent had stable disease. Median progression free survival was 1.7 months for vinorelbine and 1.6 months for gemcitabine. Median overall survival was 5.4 and 4.9 months, respectively. CONCLUSIONS: Response to second- or third-line vinorelbine or gemcitabine is rare. The high rate of stable disease warrants the continued use of these agents in this setting, though the impact on survival is questionable. These data justify the choice of placebo control arms in randomized trials of novel agents in previously treated patients.
OBJECTIVES:Pemetrexed-cisplatin is the only FDA-approved regimen for malignant pleural mesothelioma (MPM), and the impact on survival is modest. No drugs have been shown to improve survival as second-line therapy, yet vinorelbine and gemcitabine are prescribed based on the results of small phase II trials. To augment the existing limited data, we examined our institutional experience with vinorelbine and gemcitabine in patients with previously treated MPM. MATERIALS AND METHODS: We reviewed charts of patients with MPM treated with vinorelbine and/or gemcitabine as second- or third-line therapy between 2003 and 2010. Toxicity was graded according to the Common Terminology Criteria for Adverse Events Version 4.0. CT scans were reviewed with a reference radiologist according to modified RECIST criteria. RESULTS: Sixty patients were identified: 33 treated with vinorelbine, 15 gemcitabine, and 12 both agents. Eighty-three percent initially received pemetrexed-platinum. Toxicity was substantial: 46% experienced at least one episode of grade 3-4 toxicity. Of 56 patients evaluable radiologically, there was 1 partial response (gemcitabine) giving a response rate of 2% (95% CI: 0-10%). Forty-six percent had stable disease. Median progression free survival was 1.7 months for vinorelbine and 1.6 months for gemcitabine. Median overall survival was 5.4 and 4.9 months, respectively. CONCLUSIONS: Response to second- or third-line vinorelbine or gemcitabine is rare. The high rate of stable disease warrants the continued use of these agents in this setting, though the impact on survival is questionable. These data justify the choice of placebo control arms in randomized trials of novel agents in previously treated patients.
Authors: Sara Busacca; Michael Sheaff; Kenneth Arthur; Steven G Gray; Kenneth J O'Byrne; Derek J Richard; Alex Soltermann; Isabelle Opitz; Harvey Pass; D Paul Harkin; Jennifer E Quinn; Dean A Fennell Journal: J Pathol Date: 2012-03-19 Impact factor: 7.996
Authors: C Manegold; J Symanowski; U Gatzemeier; M Reck; J von Pawel; C Kortsik; K Nackaerts; P Lianes; N J Vogelzang Journal: Ann Oncol Date: 2005-04-11 Impact factor: 32.976
Authors: J P van Meerbeeck; P Baas; C Debruyne; H J Groen; C Manegold; A Ardizzoni; C Gridelli; E A van Marck; M Lentz; G Giaccone Journal: Cancer Date: 1999-06-15 Impact factor: 6.860
Authors: P A Zucali; M Perrino; E Lorenzi; G L Ceresoli; F De Vincenzo; M Simonelli; L Gianoncelli; R De Sanctis; L Giordano; A Santoro Journal: Lung Cancer Date: 2013-11-20 Impact factor: 5.705
Authors: Nicholas J Vogelzang; James J Rusthoven; James Symanowski; Claude Denham; E Kaukel; Pierre Ruffie; Ulrich Gatzemeier; Michael Boyer; Salih Emri; Christian Manegold; Clet Niyikiza; Paolo Paoletti Journal: J Clin Oncol Date: 2003-07-15 Impact factor: 44.544
Authors: Justin Stebbing; Thomas Powles; Kirsty McPherson; Jonathan Shamash; Paula Wells; Michael T Sheaff; Sarah Slater; Robin M Rudd; Dean Fennell; Jeremy P C Steele Journal: Lung Cancer Date: 2008-05-16 Impact factor: 5.705
Authors: Martin F Muers; Richard J Stephens; Patricia Fisher; Liz Darlison; Christopher M B Higgs; Erica Lowry; Andrew G Nicholson; Mary O'Brien; Michael Peake; Robin Rudd; Michael Snee; Jeremy Steele; David J Girling; Matthew Nankivell; Cheryl Pugh; Mahesh K B Parmar Journal: Lancet Date: 2008-05-17 Impact factor: 79.321
Authors: Farhad Kosari; Maria Disselhorst; Jun Yin; Tobias Peikert; Julia Udell; Sarah Johnson; James Smadbeck; Stephen Murphy; Alexa McCune; Giannoula Karagouga; Aakash Desai; Janet Schaefer-Klein; Mitesh J Borad; John Cheville; George Vasmatzis; Paul Baas; Aaron S Mansfield Journal: J Thorac Oncol Date: 2021-11-17 Impact factor: 15.609
Authors: Raffit Hassan; Anish Thomas; John J Nemunaitis; Manish R Patel; Jaafar Bennouna; Franklin L Chen; Jean-Pierre Delord; Afshin Dowlati; Samith T Kochuparambil; Matthew H Taylor; John D Powderly; Ulka N Vaishampayan; Claire Verschraegen; Hans Juergen Grote; Anja von Heydebreck; Kevin Chin; James L Gulley Journal: JAMA Oncol Date: 2019-03-01 Impact factor: 31.777
Authors: Robert A Belderbos; Paul Baas; Rossana Berardi; Robin Cornelissen; Dean A Fennell; Jan P van Meerbeeck; Arnaud Scherpereel; Heleen Vroman; Joachim G J V Aerts Journal: Transl Lung Cancer Res Date: 2019-06
Authors: Saoirse O Dolly; Andrew J Wagner; Johanna C Bendell; Hedy L Kindler; Lee M Krug; Tanguy Y Seiwert; Marjorie G Zauderer; Martijn P Lolkema; Doris Apt; Ru-Fang Yeh; Jill O Fredrickson; Jill M Spoerke; Hartmut Koeppen; Joseph A Ware; Jennifer O Lauchle; Howard A Burris; Johann S de Bono Journal: Clin Cancer Res Date: 2016-01-19 Impact factor: 12.531