Mesothelioma

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Travis Osterman, DO, MS
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13 regimens on this page
22 variants on this page

Contents


Guidelines

ASCO

ESMO

NCCN

Advanced or metastatic disease, first-line therapy

Best supportive care

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Regimen

Study Evidence Comparator Efficacy
Muers et al. 2008 (MS01) Phase III (C) 1. MVP Seems not superior
2. Vinorelbine Might have inferior OS

No antineoplastic treatment; used as a comparator arm and here for reference purposes only.

References

  1. 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

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Variant #1, limited duration

Study Evidence
Castagneto et al. 2007 Phase II

Chemotherapy

Supportive medications

21-day cycle for up to 9 cycles

Variant #2, indefinite

Study Evidence
Ceresoli et al. 2006 Phase II

Chemotherapy

Supportive medications

21-day cycles

References

  1. 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
  2. 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

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Variant #1, 75 mg/m2

Study Evidence Comparator Efficacy
Vogelzang et al. 2003 (JMCH) Phase III (C) Cisplatin & Pemetrexed Seems to have inferior OS

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

Study Evidence Comparator Efficacy
van Meerbeeck et al. 2005 (EORTC 08983/NCIC CTG BR.17) Phase III (C) Cisplatin & Raltitrexed Seems to have inferior OS

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

  1. 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
    1. 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
  2. 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

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Variant #1, 100/1000

Study Evidence
Nowak et al. 2002 Phase II

Chemotherapy

Supportive medications

28-day cycle for up to 6 cycles

Variant #2, 80/1250

Study Evidence
van Haarst et al. 2002 Phase II

Chemotherapy

Supportive medications

21-day cycle for up to 6 cycles

References

  1. 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
  2. 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

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Regimen

FDA-recommended dose
Study Evidence Comparator Efficacy
Vogelzang et al. 2003 (JMCH) Phase III (E) Cisplatin Seems to have superior OS
Zalcman et al. 2016 (MAPS) Phase III (C) PCB Seems to have inferior OS
Grosso et al. 2017 (LUME-Meso) Randomized Phase II (C) Cisplatin, Nintedanib, Pemetrexed Inferior PFS

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

  1. 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
    1. 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
  2. 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
  3. 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

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Regimen

Study Evidence Comparator Efficacy
van Meerbeeck et al. 2005 (EORTC 08983/NCIC CTG BR.17) Phase III (E) Cisplatin Seems to have superior OS

Chemotherapy

21-day cycles

References

  1. 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

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PCB: Pemetrexed, Cisplatin, Bevacizumab

Regimen

Study Evidence Comparator Efficacy
Zalcman et al. 2016 (MAPS) Phase III (E) PC Seems to have superior OS

Chemotherapy

21-day cycle for up to 6 cycles

References

  1. 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

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Regimen

Study Evidence
Taylor et al. 2008 Phase II

Chemotherapy

Supportive medications

21-day cycles

References

  1. 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

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Regimen

Study Evidence Comparator Efficacy
Muers et al. 2008 (MS01) Phase III (E) 1. Best supportive care Might have superior OS
2. MVP Seems not superior

Note: Some guidelines list the dosage as 25 to 30 mg/m2. No primary reference could be found for the 25 mg/m2 dosage.

Chemotherapy

  • Vinorelbine (Navelbine) 30 mg/m2 IV once per week x 12 weeks, with a 2-week treatment-free gap between the 6th and 7th doses

12-week course

References

  1. 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

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Regimen

Study Evidence Comparator Efficacy
Buikhuisen et al. 2013 (NVALT 5) Phase III (C) Thalidomide Seems not superior

No antineoplastic treatment after first-line therapy.

Preceding treatment

  • Pemetrexed-containing chemotherapy x 4

References

  1. 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

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Regimen

Study Evidence Comparator Efficacy
Jassem et al. 2008 Phase III (C) Pemetrexed Seems to have inferior PFS
Maio et al. 2017 (DETERMINE) Randomized Phase IIb (C) Tremelimumab Seems not superior

No antineoplastic treatment; used as a comparator arm and here for reference purposes only.

References

  1. 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
  2. DETERMINE: Maio M, Scherpereel A, Calabrò L, Aerts J, Perez SC, 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

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Variant #1, 60 mg/m2

Study Evidence Comparator Efficacy
Gregorc et al. 2018 (NGR015) Phase III (C) Doxorubicin & NGR-hTNF Seems not superior

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

Study Evidence Comparator Efficacy
Gregorc et al. 2018 (NGR015) Phase III (C) Doxorubicin & NGR-hTNF Seems not superior

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

  1. 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

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Variant #1, 1000 mg/m2</sup, 2 out of 3 weeks

Study Evidence Comparator Efficacy
Gregorc et al. 2018 (NGR015) Phase III (C) Gemcitabine & NGR-hTNF Seems not superior

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</sup, 3 out of 4 weeks

Study Evidence
Zauderer et al. 2014 Retrospective, <20 pts

Chemotherapy

28-day cycles

Variant #3, 1250 mg/m2</sup, 2 out of 3 weeks

Study Evidence Comparator Efficacy
Gregorc et al. 2018 (NGR015) Phase III (C) Gemcitabine & NGR-hTNF Seems not superior

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

  1. 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
  2. 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

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Regimen

Study Evidence
Zauderer et al. 2014 Retrospective, <20 pts

Chemotherapy

21-day cycles

References

  1. 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

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Regimen

Study Evidence Comparator Efficacy
Jassem et al. 2008 Phase III (E) Best supportive care Seems to have superior PFS

Chemotherapy

Supportive medications

21-day cycle for 8 or more cycles

References

  1. 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

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Regimen

Study Evidence Comparator Efficacy
Krug et al. 2015 (VANTAGE-014) Phase III (C) Vorinostat Seems not superior

No active antineoplastic treatment.

References

  1. 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

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Variant #1, 25 mg/m2 IV, 2 weeks out of 3

Study Evidence Comparator Efficacy
Gregorc et al. 2018 (NGR015) Phase III (C) Vinorelbine & NGR-hTNF Seems not superior

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

Study Evidence Comparator Efficacy
Gregorc et al. 2018 (NGR015) Phase III (C) Vinorelbine & NGR-hTNF Seems not superior

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.

Chemotherapy

12-week course

Variant #3, 30 mg/m2

Study Evidence
Stebbing et al. 2008 Phase II

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

Study Evidence Comparator Efficacy
Gregorc et al. 2018 (NGR015) Phase III (C) Vinorelbine & NGR-hTNF Seems not superior

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

Study Evidence Comparator Efficacy
Gregorc et al. 2018 (NGR015) Phase III (C) Vinorelbine & NGR-hTNF Seems not superior

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.

Chemotherapy

12-week course

References

  1. 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
  2. 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