Malignant pleural mesothelioma

Section editor
	Travis Osterman, DO, MS Nashville, TN Twitter: TravisOsterman LinkedIn

19 regimens on this page 33 variants on this page

Guidelines

ESMO

• 2015: Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. PubMed

NCCN

• NCCN Guidelines - Malignant Pleural Mesothelioma

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	MVP	Seems not superior
		Vinorelbine	Might have inferior OS

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

References

1. 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

• Carboplatin (Paraplatin) AUC 5 IV over 30 minutes once on day 1, given second, 30 minutes after pemetrexed
• Pemetrexed (Alimta) 500 mg/m² IV over 10 minutes once on day 1, given first

Supportive medications

• (varies depending on reference):
• Folic acid 350 to 600 mcg PO once per day, starting at least 1 week before Pemetrexed (Alimta), to continue throughout therapy
• Cyanocobalamin (Vitamin B12) 1000 mcg IM once at least 1 week before Pemetrexed (Alimta), then 1000 mcg to be given every 9 weeks thereafter
• Dexamethasone (Decadron) 4 mg PO BID the day before, the day of, and day after Pemetrexed (Alimta)
  • Alternatively, Dexamethasone (Decadron) may be given 8 mg IM the day before, the day of, and day after Pemetrexed (Alimta)
• No NSAIDs (nonsteroidal anti-inflammatory drugs) for 2 days (5 days for NSAIDs with longer half-lives) before or after Pemetrexed (Alimta)

21-day cycle for up to 9 cycles

Variant #2, indefinite

Study	Evidence
Ceresoli et al. 2006	Phase II

Chemotherapy

• Carboplatin (Paraplatin) AUC 5 IV over 30 minutes once on day 1, given second, 30 minutes after pemetrexed
• Pemetrexed (Alimta) 500 mg/m² IV over 10 minutes once on day 1, given first

Supportive medications

• (varies depending on reference):
• Folic acid 350 to 600 mcg PO once per day, starting at least 1 week before Pemetrexed (Alimta), to continue throughout therapy
• Cyanocobalamin (Vitamin B12) 1000 mcg IM once at least 1 week before Pemetrexed (Alimta), then 1000 mcg to be given every 9 weeks thereafter
• Dexamethasone (Decadron) 4 mg PO BID the day before, the day of, and day after Pemetrexed (Alimta)
  • Alternatively, Dexamethasone (Decadron) may be given 8 mg IM the day before, the day of, and day after Pemetrexed (Alimta)
• No NSAIDs (nonsteroidal anti-inflammatory drugs) for 2 days (5 days for NSAIDs with longer half-lives) before or after Pemetrexed (Alimta)

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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Regimen

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

Chemotherapy

• Cisplatin (Platinol) 75 mg/m² IV over 2 hours once on day 1

21-day cycles

References

1. 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

Cisplatin & Gemcitabine

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Variant #1, 100/1000

Study	Evidence
Nowak et al. 2002	Phase II

Chemotherapy

• Cisplatin (Platinol) 100 mg/m² IV over 60 minutes once on day 1, given first
• Gemcitabine (Gemzar) 1000 mg/m² IV over 30 minutes once per day on days 1, 8, 15, given second

Supportive medications

• Minimum of 3 liters of IV hydration for Cisplatin (Platinol), with magnesium supplementation
• 5-HT3 antagonists & Dexamethasone (Decadron) IV once per day on days 1, 8, 15 before chemotherapy
• 5-HT3 antagonists, Dexamethasone (Decadron), and/or phenothiazines for antiemesis PO or by rectal suppository for 3 to 5 days after Cisplatin (Platinol)

28-day cycle for up to 6 cycles

Variant #2, 80/1250

Study	Evidence
van Haarst et al. 2002	Phase II

Chemotherapy

• Cisplatin (Platinol) 80 mg/m² IV over 3 hours once on day 1, given second
• Gemcitabine (Gemzar) 1250 mg/m² IV over 30 minutes once per day on days 1 & 8, given first

Supportive medications

• Minimum of 2 liters of IV hydration for Cisplatin (Platinol)
• 5-HT3 antagonists before Cisplatin (Platinol)
• corticosteroids before Cisplatin (Platinol)

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

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

Note: Vogelzang et al. 2003 did not specify the total number of cycles and some patients did receive more than 6 cycles.

Chemotherapy

• Cisplatin (Platinol) 75 mg/m² IV over 2 hours once on day 1, given second, 30 minutes after pemetrexed
• Pemetrexed (Alimta) 500 mg/m² IV over 10 minutes once on day 1, given first

Supportive medications

• Folic acid 350 to 1000 mcg PO once per day, starting 1 to 3 weeks before Pemetrexed (Alimta), to continue throughout therapy
• Cyanocobalamin (Vitamin B12) 1000 mcg IM once 1 to 3 weeks before Pemetrexed (Alimta), then 1000 mcg to be given every 9 weeks thereafter
• Dexamethasone (Decadron) (dose not specified by reference) the day before, the day of, and day after Pemetrexed (Alimta)

21-day cycle for up to 6 cycles (see note)

References

1. 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. 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. 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

MVP

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MVP: Mitomycin, Vinblastine, Platinol (Cisplatin)

Regimen

Study	Evidence	Comparator	Efficacy
Muers et al. 2008 (MS01)	Phase III	Best supportive care	Seems not superior
		Vinorelbine	Seems not superior

Not considered a standard of care, included because it was a comparator arm.

Chemotherapy

• Mitomycin (Mutamycin)
• Vinblastine (Velban)
• Cisplatin (Platinol)

References

1. 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 link to PMC article PubMed

PCB

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PCB: Pemetrexed, Cisplatin, Bevacizumab

Regimen

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

Chemotherapy

• Pemetrexed (Alimta) 500 mg/m² IV once on day 1
• Cisplatin (Platinol) 75 mg/m² IV once on day 1
• Bevacizumab (Avastin) 15 mg/kg IV once on day 1

21-day cycle for up to six cycles, progression, or toxic effects

References

1. 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

• Pemetrexed (Alimta) 500 mg/m² IV over 10 minutes once on day 1

Supportive medications

• Folic acid 350 to 600 mcg PO once per day, starting 1 to 2 weeks before pemetrexed, to continue throughout therapy and at least 3 weeks after the last dose of Pemetrexed (Alimta)
• Cyanocobalamin (Vitamin B12) 1000 mcg IM once 1 to 2 weeks before Pemetrexed (Alimta), then 1000 mcg to be given every 9 weeks thereafter while continuing on pemetrexed therapy
• Dexamethasone (Decadron) 4 mg PO BID the day before, the day of, and day after Pemetrexed (Alimta)

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	Best supportive carel	Might have superior OS
		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. 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

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. 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

Gemcitabine monotherapy

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Variant #1, 21-day cycles

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

Chemotherapy

• Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1 & 8

21-day cycles

Variant #2, 28-day cycles

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

Chemotherapy

• Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1, 8, 15

28-day cycles

References

1. 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

Gemcitabine & Vinorelbine

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Regimen

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

Chemotherapy

• Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1 & 8
• Vinorelbine (Navelbine) 25 mg/m² IV once per day on days 1 & 8

21-day cycles

References

1. 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

• Pemetrexed (Alimta) 500 mg/m² IV over 10 minutes once on day 1

Supportive medications

• Folic acid 350 to 1000 mcg PO once per day, starting 1 to 2 weeks before Pemetrexed (Alimta), to continue throughout therapy and at least 3 weeks after the last dose of pemetrexed
• Cyanocobalamin (Vitamin B12) 1000 mcg IM once 1 to 2 weeks before Pemetrexed (Alimta), then 1000 mcg to be given every 9 weeks thereafter while continuing on pemetrexed therapy
• Dexamethasone (Decadron) 4 mg PO BID the day before, the day of, and day after Pemetrexed (Alimta)

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. 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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Regimen

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

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