Guidelines
Advanced or metastatic disease, first-line therapy
Best supportive care
Regimen
No antineoplastic treatment; used as a comparator arm and here for reference purposes only.
References
- MS01: Muers MF, Stephens RJ, Fisher P, Darlison L, Higgs CM, Lowry E, Nicholson AG, O'Brien M, Peake M, Rudd R, Snee M, Steele J, Girling DJ, Nankivell M, Pugh C, Parmar MK; MS01 Trial Management Group. Active symptom control with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma (MS01): a multicentre randomised trial. Lancet. 2008 May 17;371(9625):1685-94. link to original article contains verified protocol link to PMC article PubMed
Carboplatin & Pemetrexed
Variant #1, limited duration
Chemotherapy
Supportive medications
21-day cycle for up to 9 cycles
Variant #2, indefinite
Chemotherapy
Supportive medications
21-day cycles
References
- Ceresoli GL, Zucali PA, Favaretto AG, Grossi F, Bidoli P, Del Conte G, Ceribelli A, Bearz A, Morenghi E, Cavina R, Marangolo M, Parra HJ, Santoro A. Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma. J Clin Oncol. 2006 Mar 20;24(9):1443-8. link to original article contains verified protocol PubMed
- Castagneto B, Botta M, Aitini E, Spigno F, Degiovanni D, Alabiso O, Serra M, Muzio A, Carbone R, Buosi R, Galbusera V, Piccolini E, Giaretto L, Rebella L, Mencoboni M. Phase II study of pemetrexed in combination with carboplatin in patients with malignant pleural mesothelioma (MPM). Ann Oncol. 2008 Feb;19(2):370-3. Epub 2007 Dec 20. link to original article contains verified protocol PubMed
Cisplatin monotherapy
Variant #1, 75 mg/m2
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
Chemotherapy
21-day cycles
Variant #2, 80 mg/m2
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
Chemotherapy
21-day cycles
References
- JMCH: Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, Gatzemeier U, Boyer M, Emri S, Manegold C, Niyikiza C, Paoletti P. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003 Jul 15;21(14):2636-44. link to original article contains verified protocol PubMed
- Update: Manegold C, Symanowski J, Gatzemeier U, Reck M, von Pawel J, Kortsik C, Nackaerts K, Lianes P, Vogelzang NJ. Second-line (post-study) chemotherapy received by patients treated in the phase III trial of pemetrexed plus cisplatin versus cisplatin alone in malignant pleural mesothelioma. Ann Oncol. 2005 Jun;16(6):923-7. Epub 2005 Apr 11. link to original article PubMed
- EORTC 08983/NCIC CTG BR.17: van Meerbeeck JP, Gaafar R, Manegold C, Van Klaveren RJ, Van Marck EA, Vincent M, Legrand C, Bottomley A, Debruyne C, Giaccone G; European Organisation for Research and Treatment of Cancer Lung Cancer Group; National Cancer Institute of Canada. Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an intergroup study of the European Organisation for Research and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada. J Clin Oncol. 2005 Oct 1;23(28):6881-9. link to original article contains verified protocol PubMed
Cisplatin & Gemcitabine
Variant #1, 100/1000
Chemotherapy
Supportive medications
28-day cycle for up to 6 cycles
Variant #2, 80/1250
Chemotherapy
Supportive medications
21-day cycle for up to 6 cycles
References
- van Haarst JM, Baas P, Manegold Ch, Schouwink JH, Burgers JA, de Bruin HG, Mooi WJ, van Klaveren RJ, de Jonge MJ, van Meerbeeck JP. Multicentre phase II study of gemcitabine and cisplatin in malignant pleural mesothelioma. Br J Cancer. 2002 Feb 1;86(3):342-5. link to original article contains verified protocol link to PMC article PubMed content property of HemOnc.org
- Nowak AK, Byrne MJ, Williamson R, Ryan G, Segal A, Fielding D, Mitchell P, Musk AW, Robinson BW. A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma. Br J Cancer. 2002 Aug 27;87(5):491-6. link to original article contains verified protocol link to PMC article PubMed
Cisplatin & Pemetrexed
Regimen
Note: JMCH did not specify the total number of cycles and some patients did receive more than 6 cycles.
Chemotherapy
Supportive medications
21-day cycle for up to 6 cycles (see note)
References
- JMCH: Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, Gatzemeier U, Boyer M, Emri S, Manegold C, Niyikiza C, Paoletti P. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003 Jul 15;21(14):2636-44. link to original article contains verified protocol PubMed
- Update: Manegold C, Symanowski J, Gatzemeier U, Reck M, von Pawel J, Kortsik C, Nackaerts K, Lianes P, Vogelzang NJ. Second-line (post-study) chemotherapy received by patients treated in the phase III trial of pemetrexed plus cisplatin versus cisplatin alone in malignant pleural mesothelioma. Ann Oncol. 2005 Jun;16(6):923-7. Epub 2005 Apr 11. link to original article PubMed
- MAPS: Zalcman G, Mazieres J, Margery J, Greillier L, Audigier-Valette C, Moro-Sibilot D, Molinier O, Corre R, Monnet I, Gounant V, Rivière F, Janicot H, Gervais R, Locher C, Milleron B, Tran Q, Lebitasy MP, Morin F, Creveuil C, Parienti JJ, Scherpereel A; French Cooperative Thoracic Intergroup (IFCT). Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet. 2016 Apr 2;387(10026):1405-14. Epub 2015 Dec 21. Erratum in: Lancet. 2016 Apr 2;387(10026):e24. link to original article contains protocol PubMed
- LUME-Meso: Grosso F, Steele N, Novello S, Nowak AK, Popat S, Greillier L, John T, Leighl NB, Reck M, Taylor P, Planchard D, Sørensen JB, Socinski MA, von Wangenheim U, Loembé AB, Barrueco J, Morsli N, Scagliotti G. Nintedanib plus pemetrexed/cisplatin in patients with malignant pleural mesothelioma: Phase II results from the randomized, placebo-controlled LUME-Meso trial. J Clin Oncol. 2017 Nov 1;35(31):3591-3600. Epub 2017 Sep 11. link to original article contains verified protocol PubMed
Cisplatin & Raltitrexed
Regimen
Chemotherapy
21-day cycles
References
- EORTC 08983/NCIC CTG BR.17: van Meerbeeck JP, Gaafar R, Manegold C, Van Klaveren RJ, Van Marck EA, Vincent M, Legrand C, Bottomley A, Debruyne C, Giaccone G; European Organisation for Research and Treatment of Cancer Lung Cancer Group; National Cancer Institute of Canada. Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an intergroup study of the European Organisation for Research and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada. J Clin Oncol. 2005 Oct 1;23(28):6881-9. link to original article contains verified protocol PubMed
Cisplatin, Pemetrexed, Bevacizumab
PCB: Pemetrexed, Cisplatin, Bevacizumab
Regimen
Chemotherapy
21-day cycle for up to 6 cycles
References
- MAPS: Zalcman G, Mazieres J, Margery J, Greillier L, Audigier-Valette C, Moro-Sibilot D, Molinier O, Corre R, Monnet I, Gounant V, Rivière F, Janicot H, Gervais R, Locher C, Milleron B, Tran Q, Lebitasy MP, Morin F, Creveuil C, Parienti JJ, Scherpereel A; French Cooperative Thoracic Intergroup (IFCT). Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet. 2016 Apr 2;387(10026):1405-14. Epub 2015 Dec 21. Erratum in: Lancet. 2016 Apr 2;387(10026):e24. link to original article contains protocol PubMed
Pemetrexed monotherapy
Regimen
Chemotherapy
Supportive medications
21-day cycles
References
- Taylor P, Castagneto B, Dark G, Marangolo M, Scagliotti GV, van Klaveren RJ, Labianca R, Serke M, Schuette W, van Meerbeeck JP, Heigener D, Liu Y, Adachi S, Blatter J, von Pawel J. Single-agent pemetrexed for chemonaïve and pretreated patients with malignant pleural mesothelioma: results of an International Expanded Access Program. J Thorac Oncol. 2008 Jul;3(7):764-71. link to original article contains verified protocol PubMed
Vinorelbine monotherapy
Regimen
Note: Some guidelines list the dosage as 25 to 30 mg/m2. No primary reference could be found for the 25 mg/m2 dosage. Note also that it is not clear from the reference whether 11 or 12 doses were given.
Chemotherapy
7-week cycle for 2 cycles
References
- MS01: Muers MF, Stephens RJ, Fisher P, Darlison L, Higgs CM, Lowry E, Nicholson AG, O'Brien M, Peake M, Rudd R, Snee M, Steele J, Girling DJ, Nankivell M, Pugh C, Parmar MK; MS01 Trial Management Group. Active symptom control with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma (MS01): a multicentre randomised trial. Lancet. 2008 May 17;371(9625):1685-94. link to original article contains verified protocol link to PMC article PubMed
Maintenance after first line therapy
Best supportive care
Regimen
No antineoplastic treatment after first-line therapy.
Preceding treatment
- Pemetrexed-containing chemotherapy x 4
References
- NVALT 5: Buikhuisen WA, Burgers JA, Vincent AD, Korse CM, van Klaveren RJ, Schramel FM, Pavlakis N, Nowak AK, Custers FL, Schouwink JH, Gans SJ, Groen HJ, Strankinga WF, Baas P. Thalidomide versus active supportive care for maintenance in patients with malignant mesothelioma after first-line chemotherapy (NVALT 5): an open-label, multicentre, randomised phase 3 study. Lancet Oncol. 2013 May;14(6):543-51. Epub 2013 Apr 12. link to original article PubMed
Advanced or metastatic disease, subsequent lines of therapy
Best supportive care
Regimen
No antineoplastic treatment; used as a comparator arm and here for reference purposes only.
References
- Jassem J, Ramlau R, Santoro A, Schuette W, Chemaissani A, Hong S, Blatter J, Adachi S, Hanauske A, Manegold C. Phase III trial of pemetrexed plus best supportive care compared with best supportive care in previously treated patients with advanced malignant pleural mesothelioma. J Clin Oncol. 2008 Apr 1;26(10):1698-704. link to original article contains verified protocol PubMed
- DETERMINE: Maio M, Scherpereel A, Calabrò L, Aerts J, Cedres Perez S, Bearz A, Nackaerts K, Fennell DA, Kowalski D, Tsao AS, Taylor P, Grosso F, Antonia SJ, Nowak AK, Taboada M, Puglisi M, Stockman PK, Kindler HL. Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): a multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial. Lancet Oncol. 2017 Sep;18(9):1261-1273. Epub 2017 Jul 17. link to original article PubMed
Doxorubicin monotherapy
Variant #1, 60 mg/m2
Note: this is the lower bound of dosing used in NGR015. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
Chemotherapy
21-day cycle for up to 6 cycles
Variant #2, 75 mg/m2
Note: this is the upper bound of dosing used in NGR015. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
Chemotherapy
21-day cycle for up to 6 cycles
References
- NGR015: Gregorc V, Gaafar RM, Favaretto A, Grossi F, Jassem J, Polychronis A, Bidoli P, Tiseo M, Shah R, Taylor P, Novello S, Muzio A, Bearz A, Greillier L, Fontana F, Salini G, Lambiase A, O'Brien M. NGR-hTNF in combination with best investigator choice in previously treated malignant pleural mesothelioma (NGR015): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2018 Jun;19(6):799-811. Epub 2018 May 9. link to original article contains protocol PubMed
Gemcitabine monotherapy
Variant #1, 1000 mg/m2, 2 out of 3 weeks
Note: this is the lower bound of dosing used in NGR015. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
Chemotherapy
21-day cycle for up to 6 cycles
Variant #2, 1000 mg/m2, 3 out of 4 weeks
Chemotherapy
28-day cycles
Variant #3, 1250 mg/m2, 2 out of 3 weeks
Note: this is the upper bound of dosing used in NGR015. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
Chemotherapy
21-day cycle for up to 6 cycles
References
- Retrospective: Zauderer MG, Kass SL, Woo K, Sima CS, Ginsberg MS, Krug LM. Vinorelbine and gemcitabine as second- or third-line therapy for malignant pleural mesothelioma. Lung Cancer. 2014 Jun;84(3):271-4. Epub 2014 Mar 14. link to original article contains protocol link to PMC article PubMed
- NGR015: Gregorc V, Gaafar RM, Favaretto A, Grossi F, Jassem J, Polychronis A, Bidoli P, Tiseo M, Shah R, Taylor P, Novello S, Muzio A, Bearz A, Greillier L, Fontana F, Salini G, Lambiase A, O'Brien M. NGR-hTNF in combination with best investigator choice in previously treated malignant pleural mesothelioma (NGR015): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2018 Jun;19(6):799-811. Epub 2018 May 9. link to original article contains protocol PubMed
Gemcitabine & Vinorelbine
Regimen
Chemotherapy
21-day cycles
References
- Retrospective: Zauderer MG, Kass SL, Woo K, Sima CS, Ginsberg MS, Krug LM. Vinorelbine and gemcitabine as second- or third-line therapy for malignant pleural mesothelioma. Lung Cancer. 2014 Jun;84(3):271-4. Epub 2014 Mar 14. contains protocol link to PMC article PubMed
Pemetrexed monotherapy
Regimen
Chemotherapy
Supportive medications
21-day cycle for 8 or more cycles
References
- Jassem J, Ramlau R, Santoro A, Schuette W, Chemaissani A, Hong S, Blatter J, Adachi S, Hanauske A, Manegold C. Phase III trial of pemetrexed plus best supportive care compared with best supportive care in previously treated patients with advanced malignant pleural mesothelioma. J Clin Oncol. 2008 Apr 1;26(10):1698-704. link to original article contains verified protocol PubMed
Placebo
Regimen
No active antineoplastic treatment.
References
- VANTAGE-014: Krug LM, Kindler HL, Calvert H, Manegold C, Tsao AS, Fennell D, Öhman R, Plummer R, Eberhardt WE, Fukuoka K, Gaafar RM, Lafitte JJ, Hillerdal G, Chu Q, Buikhuisen WA, Lubiniecki GM, Sun X, Smith M, Baas P. Vorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Oncol. 2015 Apr;16(4):447-56. Epub 2015 Mar 20. Erratum in: Lancet Oncol. 2015 May;16(5):e199. link to original article PubMed
Vinorelbine monotherapy
Variant #1, 25 mg/m2 IV, 2 weeks out of 3
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
Chemotherapy
21-day cycle for up to 6 cycles
Variant #2, 25 mg/m2 IV, weekly
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
Chemotherapy
21-day cycle for 4 cycles
Variant #3, 30 mg/m2
Chemotherapy
- Vinorelbine (Navelbine) 30 mg/m2 (maximum of 60 mg per dose) IV over 5 minutes once per day on days 1, 8, 15, 22, 29, 36
42-day cycles
Variant #4, 60 mg/m2 PO, 2 weeks out of 3
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
Chemotherapy
21-day cycle for up to 6 cycles
Variant #5, 60 mg/m2 PO, weekly
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
Chemotherapy
21-day cycle for 4 cycles
References
- Stebbing J, Powles T, McPherson K, Shamash J, Wells P, Sheaff MT, Slater S, Rudd RM, Fennell D, Steele JP. The efficacy and safety of weekly vinorelbine in relapsed malignant pleural mesothelioma. Lung Cancer. 2009 Jan;63(1):94-7. Epub 2008 May 16. link to original article contains verified protocol PubMed
- NGR015: Gregorc V, Gaafar RM, Favaretto A, Grossi F, Jassem J, Polychronis A, Bidoli P, Tiseo M, Shah R, Taylor P, Novello S, Muzio A, Bearz A, Greillier L, Fontana F, Salini G, Lambiase A, O'Brien M. NGR-hTNF in combination with best investigator choice in previously treated malignant pleural mesothelioma (NGR015): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2018 Jun;19(6):799-811. Epub 2018 May 9. link to original article contains protocol PubMed