Revision as of 12:53, 31 December 2022

Back to Top

Section editor
	Sanjay R. Mohan, MD, MSCI Vanderbilt University Nashville, TN

0 regimens on this page 0 variants on this page

Guidelines

ELN

2011: Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet

ESMO

2015: Vannucchi et al. Philadelphia chromosome-negative chronic myeloproliferative neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

"How I Treat"

2014: Vannucchi AM. How I treat polycythemia vera. Blood. 2014 Nov 20;124(22):3212-20. Epub 2014 Oct 2. link to original article PubMed

NCCN

NCCN Guidelines - Myeloproliferative Neoplasms

First-line therapy

Aspirin monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Landolfi et al. 2004 (ECLAP)	1998-2000	Phase 3 (E-esc)	Placebo	Seems to have superior combined outcome

Anticoagulation

Aspirin 100 mg PO once per day

Continued indefinitely

References

ECLAP: Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, Barbui T; European Collaboration on Low-Dose Aspirin in Polycythemia Vera Investigators. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med. 2004 Jan 8;350(2):114-24. link to original article PubMed

Hydroxyurea monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Najean et al. 1997 (FPSG)	1980-NR	Phase 3 (E-switch-ic)	Pipobroman	Superior OS¹
Marchioli et al. 2012 (CYTO-PV)	2008-2012	Phase 3 (E-esc)	Hydroxyurea; less strict hematocrit goal	Superior primary endpont
Mascarenhas et al. 2022 (MPD-RC 112)	2011-2016	Phase 3 (C)	Peginterferon alfa-2a	Did not meet primary endpoint of CHR rate
Gisslinger et al. 2020 (PROUD-PV)	2013-2015	Phase 3 (C)	Ropeginterferon alfa-2b	Seems to have non-inferior composite endpoint

¹Reported efficacy for FPSG is based on the 2011 update.
The following is the approach recommended by Vannucchi in How I Treat (2014).

Chemotherapy

Hydroxyurea (Hydrea) 500 mg PO twice per day, with titration based on the target hematocrit and hematologic toxicity

Supportive therapy

Aspirin 81 to 100 mg PO once per day, depending on the study

Continued indefinitely

References

FPSG: Najean Y, Rain JD. Treatment of polycythemia vera: the use of hydroxyurea and pipobroman in 292 patients under the age of 65 years. Blood. 1997 Nov 1;90(9):3370-7. link to original article PubMed
1. Update: Kiladjian JJ, Chevret S, Dosquet C, Chomienne C, Rain JD. Treatment of polycythemia vera with hydroxyurea and pipobroman: final results of a randomized trial initiated in 1980. J Clin Oncol. 2011 Oct 10;29(29):3907-13. Epub 2011 Sep 12. link to original article PubMed
CYTO-PV: Marchioli R, Finazzi G, Specchia G, Cacciola R, Cavazzina R, Cilloni D, De Stefano V, Elli E, Iurlo A, Latagliata R, Lunghi F, Lunghi M, Marfisi RM, Musto P, Masciulli A, Musolino C, Cascavilla N, Quarta G, Randi ML, Rapezzi D, Ruggeri M, Rumi E, Scortechini AR, Santini S, Scarano M, Siragusa S, Spadea A, Tieghi A, Angelucci E, Visani G, Vannucchi AM, Barbui T; CYTO-PV Collaborative Group. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med. 2013 Jan 3;368(1):22-33. Epub 2012 Dec 8. link to original article PubMed NCT01645124
PROUD-PV: Gisslinger H, Klade C, Georgiev P, Krochmalczyk D, Gercheva-Kyuchukova L, Egyed M, Rossiev V, Dulicek P, Illes A, Pylypenko H, Sivcheva L, Mayer J, Yablokova V, Krejcy K, Grohmann-Izay B, Hasselbalch HC, Kralovics R, Kiladjian JJ; PROUD-PV Study Group. Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study. Lancet Haematol. 2020 Mar;7(3):e196-e208. Epub 2020 Jan 31. link to original article PubMed NCT01949805
MPD-RC 112: Mascarenhas J, Kosiorek HE, Prchal JT, Rambaldi A, Berenzon D, Yacoub A, Harrison CN, McMullin MF, Vannucchi AM, Ewing J, O'Connell CL, Kiladjian JJ, Mead AJ, Winton EF, Leibowitz DS, De Stefano V, Arcasoy MO, Kessler CM, Catchatourian R, Rondelli D, Silver RT, Bacigalupo A, Nagler A, Kremyanskaya M, Levine MF, Arango Ossa JE, McGovern E, Sandy L, Salama ME, Najfeld V, Tripodi J, Farnoud N, Penson AV, Weinberg RS, Price L, Goldberg JD, Barbui T, Marchioli R, Tognoni G, Rampal RK, Mesa RA, Dueck AC, Hoffman R. A randomized phase 3 trial of interferon-α vs hydroxyurea in polycythemia vera and essential thrombocythemia. Blood. 2022 May 12;139(19):2931-2941. link to original article contains dosing details in manuscript PubMed NCT01259856

Placebo

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Landolfi et al. 2004 (ECLAP)	1998-2000	Phase 3 (C)	Aspirin	Seems to have inferior combined outcome

No active treatment.

References

ECLAP: Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, Barbui T; European Collaboration on Low-Dose Aspirin in Polycythemia Vera Investigators. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med. 2004 Jan 8;350(2):114-24. link to original article PubMed

Ropeginterferon alfa-2b monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Gisslinger et al. 2020 (PROUD-PV)	2013-2015	Phase 3 (E-switch-ooc)	Hydroxyurea	Seems to have non-inferior composite endpoint

Immunotherapy

Ropeginterferon alfa-2b (Besremi)

References

PROUD-PV: Gisslinger H, Klade C, Georgiev P, Krochmalczyk D, Gercheva-Kyuchukova L, Egyed M, Rossiev V, Dulicek P, Illes A, Pylypenko H, Sivcheva L, Mayer J, Yablokova V, Krejcy K, Grohmann-Izay B, Hasselbalch HC, Kralovics R, Kiladjian JJ; PROUD-PV Study Group. Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study. Lancet Haematol. 2020 Mar;7(3):e196-e208. Epub 2020 Jan 31. link to original article PubMed NCT01949805

Relapsed, refractory, or intolerant

Anagrelide monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Vannucchi et al. 2015 (RESPONSE)	2010-2013	Phase 3 (C)	Ruxolitinib	Inferior disease control

To be completed

Anticoagulation

Anagrelide (Agrylin)

References

RESPONSE: Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01243944
1. Update: Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with Polycythemia Vera: 80 Week follow up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. Epub 2016 Apr 21. link to original article link to PMC article PubMed
2. Update: Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. Epub 2020 Jan 23. link to original article PubMed

Hydroxyurea monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Vannucchi et al. 2015 (RESPONSE)	2010-2013	Phase 3 (C)	Ruxolitinib	Inferior disease control

The following is the approach recommended by Vannucchi in How I Treat (2014).

Chemotherapy

Hydroxyurea (Hydrea) 500 mg PO twice per day, with titration based on the target hematocrit and hematologic toxicity

Continued indefinitely

References

RESPONSE: Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01243944
1. Update: Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with Polycythemia Vera: 80 Week follow up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. Epub 2016 Apr 21. link to original article link to PMC article PubMed
2. Update: Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. Epub 2020 Jan 23. link to original article PubMed

Lenalidomide monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Vannucchi et al. 2015 (RESPONSE)	2010-2013	Phase 3 (C)	Ruxolitinib	Inferior disease control

To be completed

Targeted therapy

Lenalidomide (Revlimid)

References

RESPONSE: Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01243944
1. Update: Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with Polycythemia Vera: 80 Week follow up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. Epub 2016 Apr 21. link to original article link to PMC article PubMed
2. Update: Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. Epub 2020 Jan 23. link to original article PubMed

Peginterferon alfa-2a monotherapy

Regimen variant #1, 45 mcg starting dose

Study	Years of enrollment	Evidence
Yacoub et al. 2019 (MPD-RC-111)	2012-2015	Phase 2

Immunotherapy

Peginterferon alfa-2a (Pegasys) 45 mcg SC once per day on days 1, 8, 15, 22
- Titrated up by 45 mcg every month in the absence of toxicity to goal dose of 180 mcg

28-day cycles

Regimen variant #2, 90 mcg starting dose

Study	Years of enrollment	Evidence
Kiladjian et al. 2008 (PVN1)	2004-2005	Phase 2
Quintás-Cardama et al. 2009 (MDACC DM03-0109)	2005-2009	Phase 2

Quintás-Cardama et al. 2009 does not provide guidance on dose escalation or target dosing. Kiladjian et al. 2008 does not provide details on the dose escalation procedure.

Immunotherapy

Peginterferon alfa-2a (Pegasys) 90 mcg SC once per day on days 1, 8, 15, 22
- Titrated up every two weeks in the absence of toxicity to 135 mcg SC once per day on days 1, 8, 15, 22
- In the absence of hematologic response, dose increased to 180 mcg SC once per day on days 1, 8, 15, 22

Supportive therapy

Aspirin 100 mg PO once per day unless intolerant (Kiladjian et al. 2008)

28-day cycles

References

PVN1: Kiladjian JJ, Cassinat B, Chevret S, Turlure P, Cambier N, Roussel M, Bellucci S, Grandchamp B, Chomienne C, Fenaux P. Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera. Blood. 2008 Oct 15;112(8):3065-72. Epub 2008 Jul 23. link to original article contains dosing details in manuscript PubMed NCT00241241
MDACC DM03-0109: Quintás-Cardama A, Kantarjian H, Manshouri T, Luthra R, Estrov Z, Pierce S, Richie MA, Borthakur G, Konopleva M, Cortes J, Verstovsek S. Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera. J Clin Oncol. 2009 Nov 10;27(32):5418-24. Epub 2009 Oct 13. link to original article contains dosing details in abstract link to PMC article PubMed NCT00452023
1. Update: Quintás-Cardama A, Abdel-Wahab O, Manshouri T, Kilpivaara O, Cortes J, Roupie AL, Zhang SJ, Harris D, Estrov Z, Kantarjian H, Levine RL, Verstovsek S. Molecular analysis of patients with polycythemia vera or essential thrombocythemia receiving pegylated interferon α-2a. Blood. 2013 Aug 8;122(6):893-901. Epub 2013 Jun 19. link to original article link to PMC article PubMed
2. Update: Masarova L, Patel KP, Newberry KJ, Cortes J, Borthakur G, Konopleva M, Estrov Z, Kantarjian H, Verstovsek S. Pegylated interferon alfa-2a in patients with essential thrombocythaemia or polycythaemia vera: a post-hoc, median 83 month follow-up of an open-label, phase 2 trial. Lancet Haematol. 2017 Apr;4(4):e165-e175. Epub 2017 Mar 10. link to original article link to PMC article PubMed
MPD-RC-111: Yacoub A, Mascarenhas J, Kosiorek H, Prchal JT, Berenzon D, Baer MR, Ritchie E, Silver RT, Kessler C, Winton E, Finazzi MC, Rambaldi A, Vannucchi AM, Leibowitz D, Rondelli D, Arcasoy MO, Catchatourian R, Vadakara J, Rosti V, Hexner E, Kremyanskaya M, Sandy L, Tripodi J, Najfeld V, Farnoud N, Papaemmanuil E, Salama M, Singer-Weinberg R, Rampal R, Goldberg JD, Barbui T, Mesa R, Dueck AC, Hoffman R. Pegylated interferon alfa-2a for polycythemia vera or essential thrombocythemia resistant or intolerant to hydroxyurea. Blood. 2019 Oct 31;134(18):1498-1509. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01259856

Pipobroman monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Vannucchi et al. 2015 (RESPONSE)	2010-2013	Phase 3 (C)	Ruxolitinib	Inferior disease control

To be completed for historical reference

Chemotherapy

Pipobroman (Vercyte)

References

Review: Passamonti F, Lazzarino M. Treatment of polycythemia vera and essential thrombocythemia: the role of pipobroman. Leuk Lymphoma. 2003 Sep;44(9):1483-8. link to original article PubMed
RESPONSE: Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01243944
1. Update: Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with Polycythemia Vera: 80 Week follow up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. Epub 2016 Apr 21. link to original article link to PMC article PubMed
2. Update: Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. Epub 2020 Jan 23. link to original article PubMed

Ruxolitinib monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Verstovsek et al. 2014 (INCB18424-256)	2008-NR	Phase 2
Vannucchi et al. 2015 (RESPONSE)	2010-2013	Phase 3 (E-RT-switch-ooc)	Standard therapy	Superior disease control
Passamonti et al. 2016 (RESPONSE-2)	2014-2015	Phase 3b (E-switch-ooc)	Standard therapy	Superior disease control

There were several doses evaluated in INCB18424-256; the median total daily dose was 21.7 mg corresponding to approximately 10 mg PO twice per day. The most common comparator in RESPONSE and RESPONSE-2 was hydroxyurea.

Targeted therapy

Ruxolitinib (Jakafi) 10 mg PO twice per day

Continued indefinitely

References

INCB18424-256: Verstovsek S, Passamonti F, Rambaldi A, Barosi G, Rosen PJ, Rumi E, Gattoni E, Pieri L, Guglielmelli P, Elena C, He S, Contel N, Mookerjee B, Sandor V, Cazzola M, Kantarjian HM, Barbui T, Vannucchi AM. A phase 2 study of ruxolitinib, an oral JAK1 and JAK2 Inhibitor, in patients with advanced polycythemia vera who are refractory or intolerant to hydroxyurea. Cancer. 2014 Feb 15;120(4):513-20. link to original article contains dosing details in manuscript link to PMC article PubMed content property of HemOnc.org NCT00726232
RESPONSE: Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01243944
1. Update: Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with Polycythemia Vera: 80 Week follow up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. Epub 2016 Apr 21. link to original article link to PMC article PubMed
2. Update: Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. Epub 2020 Jan 23. link to original article PubMed
RESPONSE-2: Passamonti F, Griesshammer M, Palandri F, Egyed M, Benevolo G, Devos T, Callum J, Vannucchi AM, Sivgin S, Bensasson C, Khan M, Mounedji N, Saydam G. Ruxolitinib for the treatment of inadequately controlled polycythaemia vera without splenomegaly (RESPONSE-2): a randomised, open-label, phase 3b study. Lancet Oncol. 2017 Jan;18(1):88-99. Epub 2016 Dec 2. link to original article contains dosing details in abstract PubMed NCT02038036
1. Update: Passamonti F, Palandri F, Saydam G, Callum J, Devos T, Guglielmelli P, Vannucchi AM, Zor E, Zuurman M, Gilotti G, Zhang Y, Griesshammer M. Ruxolitinib versus best available therapy in inadequately controlled polycythaemia vera without splenomegaly (RESPONSE-2): 5-year follow up of a randomised, phase 3b study. Lancet Haematol. 2022 Jul;9(7):e480-e492. Epub 2022 May 18. link to original article PubMed

Thalidomide monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Vannucchi et al. 2015 (RESPONSE)	2010-2013	Phase 3 (C)	Ruxolitinib	Inferior disease control

To be completed

Targeted therapy

Thalidomide (Thalomid)

References

RESPONSE: Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01243944
1. Update: Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with Polycythemia Vera: 80 Week follow up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. Epub 2016 Apr 21. link to original article link to PMC article PubMed
2. Update: Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. Epub 2020 Jan 23. link to original article PubMed

Response criteria

ELN

2009: Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference

@@ Line 3: / Line 3: @@
 [[#top|Back to Top]]
 </div>
-The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the [http://www.nccn.org/professionals/physician_gls/f_guidelines.asp NCCN Guidelines]. Is there a regimen missing from this list? See the [[Small_cell_lung_cancer|main SCLC page]] for current regimens.
+{| class="wikitable" style="text-align:center; width:50%;"
-{| class="wikitable" style="float:right; margin-right: 5px;"
+!colspan="2" align="center" style="color:white; font-size:125%; background-color:#de2d26"|'''Section editor'''
-|-
-|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
-<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
-|}
-{{TOC limit|limit=3}}
-=Limited stage, induction=
-==CAV {{#subobject:10ggc3|Regimen=1}}==
-CAV: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:4bb088|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.1993.11.7.1223 Johnson et al. 1993]
+|style="background-color:#F0F0F0"|[[File:Sanjay_mohan.png|frameless|upright=0.3|center]]
-|1982-1985
+|<big>[[User:Sanjaymohan|Sanjay R. Mohan, MD, MSCI]]<br>Vanderbilt University<br>Nashville, TN</big>
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#CAV_.26_RT|CAV & RT]]
-| style="background-color:#fee08b" |Might have inferior OS24
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+{| class="wikitable" style="float:right; margin-right: 5px;"
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> (maximum dose of 2000 mg) IV once on day 1
-*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> (maximum dose of 100 mg) IV once on day 1
-*[[Vincristine (Oncovin)]] 1 mg/m<sup>2</sup (maximum dose of 2 mg) IV once on day 1
-'''21-day cycle for 6 cycles'''
-</div></div>
-===References===
-# Johnson DH, Bass D, Einhorn LH, Crawford J, Perez CA, Bartolucci A, Omura GA, Greco FA; Southeastern Cancer Study Group. Combination chemotherapy with or without thoracic radiotherapy in limited-stage small-cell lung cancer: a randomized trial of the Southeastern Cancer Study Group. J Clin Oncol. 1993 Jul;11(7):1223-9. [https://doi.org/10.1200/JCO.1993.11.7.1223 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8391064 PubMed]
-==CAV/PE {{#subobject:106cc3|Regimen=1}}==
-CAV/PE: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine alternating with '''<u>P</u>'''latinol (Cisplatin) & '''<u>E</u>'''toposide
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:4bb088|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1200/JCO.1987.5.9.1401 Feld et al. 1987]
-|1981-1984
-| style="background-color:#1a9851" |Randomized (E-switch-ic)
-|[[#CAV-PE_99|CAV-PE]]
-| style="background-color:#ffffbf" |Did not meet efficacy endpoints
 |-
+|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
+<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+{{TOC limit|limit=3}}
-====Chemotherapy, CAV portion====
+=Guidelines=
-*[[Cyclophosphamide (Cytoxan)]] as follows:
+==ELN==
-**Cycles 1, 3, 5: 1000 mg/m<sup>2</sup> IV once on day 1
+*'''2011:''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979120/ Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet]
-*[[Doxorubicin (Adriamycin)]] as follows:
+==ESMO==
-**Cycles 1, 3, 5: 50 mg/m<sup>2</sup> IV once on day 1
+*'''2015:''' Vannucchi et al. [https://www.esmo.org/Guidelines/Haematological-Malignancies/Philadelphia-Chromosome-Negative-Chronic-Myeloproliferative-Neoplasms Philadelphia chromosome-negative chronic myeloproliferative neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
-*[[Vincristine (Oncovin)]] as follows:
+=="How I Treat"==
-**Cycles 1, 3, 5: 2 mg IV once on day 1
+*'''2014:''' Vannucchi AM. How I treat polycythemia vera. Blood. 2014 Nov 20;124(22):3212-20. Epub 2014 Oct 2. [http://www.bloodjournal.org/content/124/22/3212.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/25278584 PubMed]
-====Chemotherapy, PE portion====
+==[https://www.nccn.org/ NCCN]==
-*[[Cisplatin (Platinol)]] as follows:
+*[https://www.nccn.org/professionals/physician_gls/pdf/mpn.pdf NCCN Guidelines - Myeloproliferative Neoplasms]
-**Cycles 2, 4, 6: 25 mg/m<sup>2</sup> IV once on day 1
+=First-line therapy=
-*[[Etoposide (Vepesid)]] as follows:
+==Aspirin monotherapy {{#subobject:5c9446|Regimen=1}}==
-**Cycles 2, 4, 6: 100 mg/m<sup>2</sup> IV over 40 to 60 minutes once on day 1
-'''21-day cycle for 6 cycles'''
-</div></div>
-===References===
-# Feld R, Evans WK, Coy P, Hodson I, MacDonald AS, Osoba D, Payne D, Shelley W, Pater JL. Canadian multicenter randomized trial comparing sequential and alternating administration of two non-cross-resistant chemotherapy combinations in patients with limited small-cell carcinoma of the lung. J Clin Oncol. 1987 Sep;5(9):1401-9. [https://doi.org/10.1200/JCO.1987.5.9.1401 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/3040923 PubMed]
-==MACC {{#subobject:219cc3|Regimen=1}}==
-MACC: '''<u>M</u>'''ethotrexate, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>C</u>'''CNU (Lomustine)
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:4ee088|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1200/JCO.1985.3.7.969 Maurer et al. 1985 (CALGB 7781)]
-|1977-1981
-| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[#CCV.2FAV_88|CCV/AV]]
-| style="background-color:#ffffbf" |Did not meet endpoint of OS
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Methotrexate (MTX)]]
-*[[Doxorubicin (Adriamycin)]]
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Lomustine (CCNU)]]
-</div></div>
-===References===
-# '''CALGB 7781:''' Maurer LH, Pajak T, Eaton W, Comis R, Chahinian P, Faulkner C, Silberfarb PM, Henderson E, Rege VB, Baldwin PE, Weiss R, Rafla S, Prager D, Carey R, Perry M, Choi NC. Combined modality therapy with radiotherapy, chemotherapy, and immunotherapy in limited small-cell carcinoma of the lung: a Phase III Cancer and Leukemia Group B Study. J Clin Oncol. 1985 Jul;3(7):969-76. [https://doi.org/10.1200/JCO.1985.3.7.969 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2991478 PubMed]
-==VMV-VAC {{#subobject:139cc3|Regimen=1}}==
-VMV-VAC: '''<u>V</u>'''incristine, '''<u>M</u>'''ethotrexate, '''<u>V</u>'''P-16 (Etoposide), '''<u>V</u>'''P-16 (Etoposide),  '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:4cc088|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://doi.org/10.1200/JCO.1987.5.4.592 Kies et al. 1987]
-| style="background-color:#91cf61" |Non-randomized portion of RCT
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Vincristine (Oncovin)]]
-*[[Methotrexate (MTX)]]
-*[[Etoposide (Vepesid)]]
-*[[Doxorubicin (Adriamycin)]]
-*[[Cyclophosphamide (Cytoxan)]]
-</div></div>
-===References===
-# Kies MS, Mira JG, Crowley JJ, Chen TT, Pazdur R, Grozea PN, Rivkin SE, Coltman CA Jr, Ward JH, Livingston RB; [[Study_Groups#SWOG|SWOG]]. Multimodal therapy for limited small-cell lung cancer: a randomized study of induction combination chemotherapy with or without thoracic radiation in complete responders; and with wide-field versus reduced-field radiation in partial responders: a Southwest Oncology Group study. J Clin Oncol. 1987 Apr;5(4):592-600. [https://doi.org/10.1200/JCO.1987.5.4.592 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3031226 PubMed]
-=Limited stage, definitive chemoradiotherapy=
-==CC/DE & RT {{#subobject:189bcc|Regimen=1}}==
-CC/DE & RT: '''<u>C</u>'''yclophosphamide & '''<u>C</u>'''isplatin alternating with '''<u>D</u>'''oxorubicin & '''<u>E</u>'''toposide, with '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:dd9b40|Variant=1}}===
+===Regimen {{#subobject:3983e0|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 134: / Line 36: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1056/NEJM199312163292504 Arriagada et al. 1993]
+|[https://doi.org/10.1056/nejmoa035572 Landolfi et al. 2004 (ECLAP)]
-|1988-1991
+|1998-2000
 | style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#CC.2FDE_.26_RT|CC/DE & RT]]; lower-dose
+|[[#Placebo|Placebo]]
-| style="background-color:#91cf60" |Seems to have superior OS
+| style="background-color:#91cf60" |Seems to have superior combined outcome
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
+====Anticoagulation====
-*[[Cyclophosphamide (Cytoxan)]]
+*[[Aspirin]] 100 mg PO once per day
-*[[Cisplatin (Platinol)]]
+'''Continued indefinitely'''
-*[[Doxorubicin (Adriamycin)]]
-*[[Etoposide (Vepesid)]]
-====Radiotherapy====
-*[[External beam radiotherapy]]
 </div></div>
 ===References===
-# Arriagada R, Le Chevalier T, Pignon JP, Rivière A, Monnet I, Chomy P, Tuchais C, Tarayre M, Ruffié P. Initial chemotherapeutic doses and survival in patients with limited small-cell lung cancer. N Engl J Med. 1993 Dec 16;329(25):1848-52. [https://doi.org/10.1056/NEJM199312163292504 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8247036 PubMed]
+# '''ECLAP:''' Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, Barbui T; European Collaboration on Low-Dose Aspirin in Polycythemia Vera Investigators. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med. 2004 Jan 8;350(2):114-24. [https://doi.org/10.1056/nejmoa035572 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14711910 PubMed]
-==CAV & RT {{#subobject:a37yf8|Regimen=1}}==
+==Hydroxyurea monotherapy {{#subobject:511984|Regimen=1}}==
-CAV & RT: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine, '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:8801k9|Variant=1}}===
+===Regimen {{#subobject:84f020|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 163: / Line 60: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/jco.1984.2.11.1200 Perez et al. 1984]
+|[http://www.bloodjournal.org/content/90/9/3370.long Najean et al. 1997 (FPSG)]
-|1978-1982
+|1980-NR
-| style="background-color:#1a9851" |Randomized (E-esc)
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
-|[[#CAV|CAV]]
+|[[#Pipobroman_monotherapy_88|Pipobroman]]
-| style="background-color:#d9ef8b" |Might have superior DFS<sup>1</sup>
+|style="background-color:#1a9850"|Superior OS<sup>1</sup>
 |-
-|[https://doi.org/10.1200/JCO.1990.8.1.33 Jett et al. 1990]
+|[https://doi.org/10.1056/nejmoa1208500 Marchioli et al. 2012 (CYTO-PV)]
-|1979-1986
+|2008-2012
-| style="background-color:#1a9851" |Randomized (C)
+|style="background-color:#1a9851"|Phase 3 (E-esc)
-|[[#CAVE_.26_RT_99|CAVE & RT]]
+|[[#Hydroxyurea_monotherapy|Hydroxyurea]]; less strict hematocrit goal
-| style="background-color:#ffffbf" |Did not meet endpoint of OS
+|style="background-color:#1a9850"|Superior primary endpont
 |-
-|[https://doi.org/10.1200/JCO.1993.11.7.1223 Johnson et al. 1993]
+|[https://doi.org/10.1182/blood.2021012743 Mascarenhas et al. 2022 (MPD-RC 112)]
-|1982-1985
+|2011-2016
-| style="background-color:#1a9851" |Phase 3 (E-esc)
+|style="background-color:#1a9851"|Phase 3 (C)
-|[[#CAV|CAV]]
+|[[#Pegintereron_alfa-2a_monotherapy_99|Peginterferon alfa-2a]]
-| style="background-color:#d9ef8b" |Might have superior OS24<br>OS24: 33% vs 23.5%
+| style="background-color:#ffffbf" |Did not meet primary endpoint of CHR rate
 |-
-|}
+|[https://doi.org/10.1016/s2352-3026(19)30236-4 Gisslinger et al. 2020 (PROUD-PV)]
-''<sup>1</sup>It is not clear from the manuscript what the primary endpont of the study was.''
+|2013-2015
-<div class="toccolours" style="background-color:#b3e2cd">
+|style="background-color:#1a9851"|Phase 3 (C)
-====Chemotherapy====
+|[[#Ropeginterferon_alfa-2b_monotherapy_77|Ropeginterferon alfa-2b]]
-*[[Cyclophosphamide (Cytoxan)]]
+| style="background-color:#eeee01" |Seems to have non-inferior composite endpoint
-*[[Doxorubicin (Adriamycin)]]
-*[[Vincristine (Oncovin)]]
-====Radiotherapy====
-*Concurrent [[External_beam_radiotherapy|radiation therapy]]
-</div></div>
-===References===
-# Perez CA, Einhorn L, Oldham RK, Greco FA, Cohen HJ, Silberman H, Krauss S, Hornback N, Comas F, Omura G, Salter M, Keller JW, McLaren J, Kellermeyer R, Storaasli J, Birch R, Dandy M; Southeastern Cancer Study Group. Randomized trial of radiotherapy to the thorax in limited small-cell carcinoma of the lung treated with multiagent chemotherapy and elective brain irradiation: a preliminary report. J Clin Oncol. 1984 Nov;2(11):1200-8. [https://doi.org/10.1200/jco.1984.2.11.1200 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6092555/ PubMed]
-# Jett JR, Everson L, Therneau TM, Krook JE, Dalton RJ, Marschke RF Jr, Veeder MH, Brunk SF, Mailliard JA, Twito DI, Earle JD, Anderson RT; North Central Cancer Treatment Group. Treatment of limited-stage small-cell lung cancer with cyclophosphamide, doxorubicin, and vincristine with or without etoposide: a randomized trial of the North Central Cancer Treatment Group. J Clin Oncol. 1990 Jan;8(1):33-8. [https://doi.org/10.1200/JCO.1990.8.1.33 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2153193 PubMed]
-# Johnson DH, Bass D, Einhorn LH, Crawford J, Perez CA, Bartolucci A, Omura GA, Greco FA; Southeastern Cancer Study Group. Combination chemotherapy with or without thoracic radiotherapy in limited-stage small-cell lung cancer: a randomized trial of the Southeastern Cancer Study Group. J Clin Oncol. 1993 Jul;11(7):1223-9. [https://doi.org/10.1200/JCO.1993.11.7.1223 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8391064 PubMed]
-==CEV & RT {{#subobject:a3e998|Regimen=1}}==
-CEV & RT: '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''pirubicin, '''<u>V</u>'''incristine, '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:88c1d9|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|rowspan=2|[https://doi.org/10.1056/NEJM198704093161504 Perry et al. 1987 (CALGB 8083)]
-|rowspan=2|1981-1984
-|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc)
-|1. [[#CEV_.28Cyclophosphamide.2FEpirubicin.29|CEV]]
-| style="background-color:#1a9850" |Superior OS
-|-
-|2. [[#CEV_.28Cyclophosphamide.2FEpirubicin.29|CEV]], then [[#Radiation_therapy_88|RT]]
-| style="background-color:#d3d3d3" |Not reported
-|-
-|[https://doi.org/10.1200/jco.2002.12.111 Sundstrøm et al. 2002]
-|1989-1994
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[Small_cell_lung_cancer#Cisplatin.2C_Etoposide.2C_RT|Cisplatin, Etoposide, RT]]
-| style="background-color:#d73027" |Inferior OS
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''<sup>1</sup>Reported efficacy for FPSG is based on the 2011 update.''<br>
+''The following is the approach recommended by Vannucchi in How I Treat (2014).''
 ====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]]
+*[[Hydroxyurea (Hydrea)]] 500 mg PO twice per day, with titration based on the target hematocrit and hematologic toxicity
-*[[Epirubicin (Ellence)]]
+====Supportive therapy====
-*[[Vincristine (Oncovin)]]
+*[[Aspirin]] 81 to 100 mg PO once per day, depending on the study
-====Radiotherapy====
+'''Continued indefinitely'''
-*Concurrent [[External_beam_radiotherapy|radiation therapy]]
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*Patients with CR: [[Small_cell_lung_cancer#Whole_brain_irradiation|Prophylactic cranial irradiation]]
-</div></div>
-===References===
-# '''CALGB 8083:''' Perry MC, Eaton WL, Propert KJ, Ware JH, Zimmer B, Chahinian AP, Skarin A, Carey RW, Kreisman H, Faulkner C, Comis R, Green MR. Chemotherapy with or without radiation therapy in limited small-cell carcinoma of the lung. N Engl J Med. 1987 Apr 9;316(15):912-8. [https://doi.org/10.1056/NEJM198704093161504 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3029592 PubMed]
-# Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002 Dec 15;20(24):4665-72. [https://doi.org/10.1200/jco.2002.12.111 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12488411 PubMed]
-==Methotrexate, RT, Cyclophosphamide {{#subobject:a4e998|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Protocol {{#subobject:78c1d9|Variant=1}}===
-{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://doi.org/10.1016/s0140-6736(82)92099-2 Thatcher et al. 1982]
-|1978-1981
-| style="background-color:#91cf61" |Non-randomized portion of RCT
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy, part 1====
-*[[Methotrexate (MTX)]]
-====Radiotherapy====
-*[[External_beam_radiotherapy|Radiation therapy]]
-====Chemotherapy, part 2====
-*[[Cyclophosphamide (Cytoxan)]]
 </div></div>
 ===References===
-# Thatcher N, Barber PV, Hunter RD, Carroll KB, Jegarajah S, Wilkinson PM, Crowther D; Manchester Lung Tumour Group. 11-week course of sequential methotrexate, thoracic irradiation, and moderate-dose cyclophosphamide for "limited"-stage small-cell bronchogenic carcinoma: a study from the Manchester Lung Tumour Group. Lancet. 1982 May 8;1(8280):1040-3. [https://doi.org/10.1016/s0140-6736(82)92099-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6122853 PubMed]
+# '''FPSG:''' Najean Y, Rain JD. Treatment of polycythemia vera: the use of hydroxyurea and pipobroman in 292 patients under the age of 65 years. Blood. 1997 Nov 1;90(9):3370-7. [http://www.bloodjournal.org/content/90/9/3370.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/9345019 PubMed]
-=Extensive stage, induction=
+## '''Update:''' Kiladjian JJ, Chevret S, Dosquet C, Chomienne C, Rain JD. Treatment of polycythemia vera with hydroxyurea and pipobroman: final results of a randomized trial initiated in 1980. J Clin Oncol. 2011 Oct 10;29(29):3907-13. Epub 2011 Sep 12. [https://doi.org/10.1200/JCO.2011.36.0792 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21911721 PubMed]
-==ACE {{#subobject:9fbf31|Regimen=1}}==
+# '''CYTO-PV:''' Marchioli R, Finazzi G, Specchia G, Cacciola R, Cavazzina R, Cilloni D, De Stefano V, Elli E, Iurlo A, Latagliata R, Lunghi F, Lunghi M, Marfisi RM, Musto P, Masciulli A, Musolino C, Cascavilla N, Quarta G, Randi ML, Rapezzi D, Ruggeri M, Rumi E, Scortechini AR, Santini S, Scarano M, Siragusa S, Spadea A, Tieghi A, Angelucci E, Visani G, Vannucchi AM, Barbui T; CYTO-PV Collaborative Group. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med. 2013 Jan 3;368(1):22-33. Epub 2012 Dec 8. [https://doi.org/10.1056/nejmoa1208500 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23216616 PubMed] NCT01645124
-ACE: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide
+# '''PROUD-PV:''' Gisslinger H, Klade C, Georgiev P, Krochmalczyk D, Gercheva-Kyuchukova L, Egyed M, Rossiev V, Dulicek P, Illes A, Pylypenko H, Sivcheva L, Mayer J, Yablokova V, Krejcy K, Grohmann-Izay B, Hasselbalch HC, Kralovics R, Kiladjian JJ; PROUD-PV Study Group. Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study. Lancet Haematol. 2020 Mar;7(3):e196-e208. Epub 2020 Jan 31. [https://doi.org/10.1016/s2352-3026(19)30236-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32014125 PubMed] NCT01949805
-<br>AVE: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''epesid (Etoposide), '''<u>E</u>'''ndoxan (Cyclophosphamide)
+# '''MPD-RC 112:''' Mascarenhas J, Kosiorek HE, Prchal JT, Rambaldi A, Berenzon D, Yacoub A, Harrison CN, McMullin MF, Vannucchi AM, Ewing J, O'Connell CL, Kiladjian JJ, Mead AJ, Winton EF, Leibowitz DS, De Stefano V, Arcasoy MO, Kessler CM, Catchatourian R, Rondelli D, Silver RT, Bacigalupo A, Nagler A, Kremyanskaya M, Levine MF, Arango Ossa JE, McGovern E, Sandy L, Salama ME, Najfeld V, Tripodi J, Farnoud N, Penson AV, Weinberg RS, Price L, Goldberg JD, Barbui T, Marchioli R, Tognoni G, Rampal RK, Mesa RA, Dueck AC, Hoffman R. A randomized phase 3 trial of interferon-α vs hydroxyurea in polycythemia vera and essential thrombocythemia. Blood. 2022 May 12;139(19):2931-2941. [https://doi.org/10.1182/blood.2021012743 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35007321/ PubMed] NCT01259856
-<br>CAE: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>E</u>'''toposide
+==Placebo==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:949381|Variant=1}}===
+===Regimen===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 274: / Line 109: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1002/1097-0142%2819850701%2956%3A1%3C71%3A%3AAID-CNCR2820560112%3E3.0.CO%3B2-9 Klastersky et al. 1985]
+|[https://doi.org/10.1056/nejmoa035572 Landolfi et al. 2004 (ECLAP)]
-|NR
+|1998-2000
-| style="background-color:#91cf61" |Phase 2
-| style="background-color:#d3d3d3" |
-| ORR: 66%
-|-
-|[https://doi.org/10.1200/JCO.1993.11.10.1858 Sculier et al. 1993]
-|1987-NR
-| style="background-color:#1a9851" |Phase 3 (C)
-|Multi-drug regimen
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527803/ Baka et al. 2008]
-|1999-2005
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[Small_cell_lung_cancer#Cisplatin_.26_Etoposide_.28EP.29_2|EP]]
+|[[#Aspirin_monotherapy|Aspirin]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS12
+| style="background-color:#fc8d59" |Seems to have inferior combined outcome
-|-
-|}
-''Used as a comparator arm in older studies. The non-randomized results of Klastersky et al. 1985 established this regimen as a standard control.''
-====Chemotherapy====
-*[[Doxorubicin (Adriamycin)]]
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Etoposide (Vepesid)]]
-</div></div>
-===References===
-# Klastersky J, Sculier JP, Dumont JP, Becquart D, Vandermoten G, Rocmans P, Michel J, Longeval E, Dalesio O. Combination chemotherapy with adriamycin, etoposide, and cyclophosphamide for small cell carcinoma of the lung: a study by the EORTC Lung Cancer Working Party (Belgium). Cancer. 1985 Jul 1;56(1):71-5. [https://doi.org/10.1002/1097-0142%2819850701%2956%3A1%3C71%3A%3AAID-CNCR2820560112%3E3.0.CO%3B2-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2988738 PubMed]
-# Sculier JP, Paesmans M, Bureau G, Dabouis G, Libert P, Vandermoten G, Van Cutsem O, Berchier MC, Ries F, Michel J, Sergysels R, Mommen P, Klastersky J. Multiple-drug weekly chemotherapy versus standard combination regimen in small-cell lung cancer: a phase III randomized study conducted by the European Lung Cancer Working Party. J Clin Oncol. 1993 Oct;11(10):1858-65. [https://doi.org/10.1200/JCO.1993.11.10.1858 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8410110 PubMed]
-# Baka S, Califano R, Ferraldeschi R, Aschroft L, Thatcher N, Taylor P, Faivre-Finn C, Blackhall F, Lorigan P. Phase III randomised trial of doxorubicin-based chemotherapy compared with platinum-based chemotherapy in small-cell lung cancer. Br J Cancer. 2008 Aug 5;99(3):442-7. [https://doi.org/10.1038/sj.bjc.6604480 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527803/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18665190 PubMed]
-==BACO {{#subobject:8b52ad|Regimen=1}}==
-BACO: '''<u>B</u>'''leomycin, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine)
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:e3138e|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://doi.org/10.1001/jama.1976.03260380019019 Einhorn et al. 1976]
-| style="background-color:#91cf61" |Non-randomized
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''No active treatment.''
-====Chemotherapy====
-*[[Bleomycin (Blenoxane)]]
-*[[Doxorubicin (Adriamycin)]]
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Vincristine (Oncovin)]]
 </div></div>
 ===References===
-# Einhorn LH, Fee WH, Farber MO, Livingston RB, Gottlieb JA. Improved chemotherapy for small-cell undifferentiated lung cancer. JAMA. 1976 Mar 22;235(12):1225-9. [https://doi.org/10.1001/jama.1976.03260380019019 link to original article] [https://pubmed.ncbi.nlm.nih.gov/55504 PubMed]
+# '''ECLAP:''' Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, Barbui T; European Collaboration on Low-Dose Aspirin in Polycythemia Vera Investigators. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med. 2004 Jan 8;350(2):114-24. [https://doi.org/10.1056/nejmoa035572 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14711910 PubMed]
-==Carboplatin & Etoposide (CE) & Pembrolizumab {{#subobject:o9ga26|Regimen=1}}==
+==Ropeginterferon alfa-2b monotherapy {{#subobject:5kgix4|Regimen=1}}==
-CE & Pembrolizumab: '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide, Pembrolizumab
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:3cn73m|Variant=1}}===
+===Regimen {{#subobject:cob120|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 335: / Line 130: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7474472/ Rudin et al. 2020 (KEYNOTE-604)]
+|[https://doi.org/10.1016/s2352-3026(19)30236-4 Gisslinger et al. 2020 (PROUD-PV)]
-|2017-2018
+|2013-2015
-|style="background-color:#1a9851" |Phase 3 (E-esc)
+|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
-|1a. [[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]<br>1b. [[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]
+|[[#Hydroxyurea_monotherapy|Hydroxyurea]]
-| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup><br>OS24: 22.5% vs 11.2%<br>(HR 0.80, 95% CI 0.64-0.98)
+| style="background-color:#eeee01" |Seems to have non-inferior composite endpoint
 |-
 |}
-''<sup>1</sup>This result did not meet the pre-specified threshold for statistical significance, and was the basis for withdrawal of the FDA indication.''
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Carboplatin (Paraplatin)]] as follows:
-**Cycles 1 to 4: AUC 5 IV once on day 1
-*[[Etoposide (Vepesid)]] as follows:
-**Cycles 1 to 4: 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
 ====Immunotherapy====
-*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
+*[[Ropeginterferon alfa-2b (Besremi)]]
-'''21-day cycle for up to 35 cycles (2 years)'''
-</div></div>
-===References===
-# '''KEYNOTE-604:''' Rudin CM, Awad MM, Navarro A, Gottfried M, Peters S, Csőszi T, Cheema PK, Rodriguez-Abreu D, Wollner M, Yang JC, Mazieres J, Orlandi FJ, Luft A, Gümüş M, Kato T, Kalemkerian GP, Luo Y, Ebiana V, Pietanza MC, Kim HR; KEYNOTE-604 Investigators. Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study. J Clin Oncol. 2020 Jul 20;38(21):2369-2379. Epub 2020 May 29. [https://doi.org/10.1200/jco.20.00793 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7474472/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32468956/ PubMed] NCT03066778
-==CAV {{#subobject:cbb2ff|Regimen=1}}==
-CAV: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine
-<br> CAO: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine)
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 1000/40/1, capped by BSA {{#subobject:51b1f9|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 17%"|Study
-!style="width: 15%"|Years of enrollment
-!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 17%"|Comparator
-!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
-|-
-|[https://pubmed.ncbi.nlm.nih.gov/3020700 Bunn et al. 1986]
-|NR in abstract
-| style="background-color:#1a9851" |Randomized (C)
-|[[#CDE|CDE]]
-| style="background-color:#fc8d59" |Seems to have inferior OS
-|
-|-
-|[https://doi.org/10.1200/JCO.1987.5.11.1731 Johnson et al. 1987]
-|1982-1984
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#CAV_2|CAV]]; high-dose
-| style="background-color:#ffffbf" |Did not meet endpoint of OS
-| style="background-color:#1a9850" |Less toxic
-|-
-|}
-''Note: the original manuscript with dosing for Bunn et al. 1986 is not available for review.''
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> (maximum dose of 2000 mg) IV once on day 1
-*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> (maximum dose of 80 mg) IV once on day 1
-*[[Vincristine (Oncovin)]] 1 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
-'''21-day cycle for 6 cycles'''
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, 1000/50/1.4, uncapped vincristine {{#subobject:d8e9d5|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 17%"|Study
-!style="width: 15%"|Years of enrollment
-!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 17%"|Comparator
-!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
-|-
-|[https://doi.org/10.1200/JCO.1990.8.2.230 Ettinger et al. 1990]
-|1982-1985
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#CAV.2FHEM_88|CAV/HEM]]
-| style="background-color:#d73027" |Inferior OS
-|
-|-
-| rowspan="2" |[https://doi.org/10.1016/s0169-5002(02)00074-0 Ettinger et al. 2002 (ECOG E1588)]
-|rowspan=2|1988-1990
-| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
-|1. [[Small_cell_lung_cancer#Ifosfamide_monotherapy|Ifosfamide]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-| style="background-color:#d73027" |More toxic
-|-
-|2. [[Small_cell_lung_cancer#Teniposide_monotherapy|Teniposide]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-| style="background-color:#d73027" |More toxic
-|-
-|[https://doi.org/10.1016/S0140-6736(96)02005-3 Girling 1996]
-|1992-1995
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Etoposide_monotherapy|Etoposide]]; oral
-| style="background-color:#91cf60" |Seems to have superior OS
-|
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1
-*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
-*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1
-'''21-day cycle for 4 to 6 cycles'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*ECOG E1588, CR: [[#CAV_2|CAV]] x 2 (6 to 8 total), then [[#Whole_brain_irradiation_2|PCI]]
-*ECOG E1588, PR: [[#CAV_2|CAV]] until progression of disease, then salvage [[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #3, 1000/50/2, flat-dose vincristine {{#subobject:3dc31b|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 17%"|Study
-!style="width: 15%"|Years of enrollment
-!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 17%"|Comparator
-!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
-|-
-|[https://jamanetwork.com/journals/jama/article-abstract/352016 Holoye et al. 1977]
-|1973-1974
-| style="background-color:#91cf61" |Non-randomized
-| style="background-color:#d3d3d3" |
-| style="background-color:#d3d3d3" |
-| style="background-color:#d3d3d3" |
-|-
-|[https://doi.org/10.7326/0003-4819-107-4-451 Evans et al. 1987]
-|1982-1985
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#CAV.2FPE|CAV/PE]]
-| style="background-color:#fc8d59" |Seems to have inferior OS
-| style="background-color:#ffffbf" |Similar toxicity
-|-
-|[https://doi.org/10.1200/JCO.1994.12.1.70 Maksymiuk et al. 1994]
-|1987-1990
-| style="background-color:#91cf61" |Non-randomized portion of RCT
-| style="background-color:#d3d3d3" |
-| style="background-color:#d3d3d3" |
-| style="background-color:#d3d3d3" |
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1
-*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
-*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
-'''21-day cycle for 6 cycles'''
 </div></div>
 ===References===
-# Holoye PY, Samuels ML, Lanzotti VJ, Smith T, Barkley HT Jr. Combination chemotherapy and radiation therapy for small cell carcinoma. JAMA. 1977 Mar 21;237(12):1221-4. [https://jamanetwork.com/journals/jama/article-abstract/352016 link to original article] [https://pubmed.ncbi.nlm.nih.gov/190427 PubMed]
+# '''PROUD-PV:''' Gisslinger H, Klade C, Georgiev P, Krochmalczyk D, Gercheva-Kyuchukova L, Egyed M, Rossiev V, Dulicek P, Illes A, Pylypenko H, Sivcheva L, Mayer J, Yablokova V, Krejcy K, Grohmann-Izay B, Hasselbalch HC, Kralovics R, Kiladjian JJ; PROUD-PV Study Group. Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study. Lancet Haematol. 2020 Mar;7(3):e196-e208. Epub 2020 Jan 31. [https://doi.org/10.1016/s2352-3026(19)30236-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32014125 PubMed] NCT01949805
-# Bunn PA Jr, Greco FA, Einhorn L. Cyclophosphamide, doxorubicin, and etoposide as first-line therapy in the treatment of small-cell lung cancer. Semin Oncol. 1986 Sep;13(3 Suppl 3):45-53. [https://pubmed.ncbi.nlm.nih.gov/3020700 PubMed]
+=Relapsed, refractory, or intolerant=
-# Evans WK, Feld R, Murray N, Willan A, Coy P, Osoba D, Shepherd FA, Clark DA, Levitt M, MacDonald A, Wilson K, Shelley W, Pater J. Superiority of alternating non-cross-resistant chemotherapy in extensive small cell lung cancer: a multicenter, randomized clinical trial by the National Cancer Institute of Canada. Ann Intern Med. 1987 Oct;107(4):451-8. Erratum in: Ann Intern Med 1988 Mar;108(3):496. [https://doi.org/10.7326/0003-4819-107-4-451 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/2820289 PubMed]
+==Anagrelide monotherapy {{#subobject:7c6a2d|Regimen=1}}==
-# Johnson DH, Einhorn LH, Birch R, Vollmer R, Perez C, Krauss S, Omura G, Greco FA; Southeastern Cancer Study Group. A randomized comparison of high-dose versus conventional-dose cyclophosphamide, doxorubicin, and vincristine for extensive-stage small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group. J Clin Oncol. 1987 Nov;5(11):1731-8. [https://doi.org/10.1200/JCO.1987.5.11.1731 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2824707 PubMed]
-# Ettinger DS, Finkelstein DM, Abeloff MD, Ruckdeschel JC, Aisner SC, Eggleston JC; [[Study_Groups#ECOG|ECOG]]. A randomized comparison of standard chemotherapy versus alternating chemotherapy and maintenance versus no maintenance therapy for extensive-stage small-cell lung cancer: a phase III study of the Eastern Cooperative Oncology Group. J Clin Oncol. 1990 Feb;8(2):230-40. [https://doi.org/10.1200/JCO.1990.8.2.230 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2153765 PubMed]
-# Maksymiuk AW, Jett JR, Earle JD, Su JQ, Diegert FA, Mailliard JA, Kardinal CG, Krook JE, Veeder MH, Wiesenfeld M, Tschetter LK, Levitt R; North Central Cancer Treatment Group. Sequencing and schedule effects of cisplatin plus etoposide in small-cell lung cancer: results of a North Central Cancer Treatment Group randomized clinical trial. J Clin Oncol. 1994 Jan;12(1):70-6. [https://doi.org/10.1200/JCO.1994.12.1.70 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8270988 PubMed]
-# Girling DJ; Medical Research Council Lung Cancer Working Party. Comparison of oral etoposide and standard intravenous multidrug chemotherapy for small-cell lung cancer: a stopped multicentre randomised trial. Lancet. 1996 Aug 31;348(9027):563-6. [https://doi.org/10.1016/S0140-6736(96)02005-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8774567 PubMed]
-# '''ECOG E1588:''' Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; [[Study_Groups#ECOG|ECOG]]. Study of either ifosfamide or teniposide compared to a standard chemotherapy for extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group randomized study (E1588). Lung Cancer. 2002 Sep;37(3):311-8. [https://doi.org/10.1016/s0169-5002(02)00074-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12234701 PubMed]
-==CAV/PE {{#subobject:55aede|Regimen=1}}==
-CAV/PE: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine alternating with '''<u>P</u>'''latinol (Cisplatin) & '''<u>E</u>'''toposide
 <div class="toccolours" style="background-color:#eeeeee">
-===Protocol {{#subobject:2a8dee|Variant=1}}===
+===Regimen {{#subobject:50dda2|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 498: / Line 154: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.1990.8.1.39 Goodman et al. 1990 (SWOG S8232)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ Vannucchi et al. 2015 (RESPONSE)]
-|1982-1984
+|2010-2013
-| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+|style="background-color:#1a9851"|Phase 3 (C)
-|[[#CAVE|CAVE]]
+|[[#Ruxolitinib_monotherapy|Ruxolitinib]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|style="background-color:#d73027"|Inferior disease control
-|-
-|[https://doi.org/10.7326/0003-4819-107-4-451 Evans et al. 1987]
-|1982-1985
-| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[#CAV_2|CAV]]
-| style="background-color:#91cf60" |Seems to have superior OS
-|-
-|[https://doi.org/10.1200/JCO.1992.10.2.282 Roth et al. 1992]
-|1985-1989
-| style="background-color:#1a9851" |Phase 3 (E-esc)
-|1. [[#CAV_2|CAV]]<br>2. [[Small_cell_lung_cancer#Cisplatin_.26_Etoposide_.28EP.29_2|EP]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS50%
-|-
-|[https://doi.org/10.1200/JCO.1998.16.6.2126 Furuse et al. 1998 (JCOG9106)]
-|1991-1995
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[Stub#CODE|CODE]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS50%
-|-
-|[https://doi.org/10.1200/JCO.1999.17.8.2300 Murray et al. 1999]
-|1992-1996
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[Stub#CODE|CODE]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+To be completed
-====Chemotherapy, CAV portion====
+====Anticoagulation====
-*[[Cyclophosphamide (Cytoxan)]]
+*[[Anagrelide (Agrylin)]]
-*[[Doxorubicin (Adriamycin)]]
-*[[Vincristine (Oncovin)]]
-====Chemotherapy, PE portion====
-*[[Cisplatin (Platinol)]]
-*[[Etoposide (Vepesid)]]
 </div></div>
 ===References===
-# Evans WK, Feld R, Murray N, Willan A, Coy P, Osoba D, Shepherd FA, Clark DA, Levitt M, MacDonald A, Wilson K, Shelley W, Pater J. Superiority of alternating non-cross-resistant chemotherapy in extensive small cell lung cancer: a multicenter, randomized clinical trial by the National Cancer Institute of Canada. Ann Intern Med. 1987 Oct;107(4):451-8. Erratum in: Ann Intern Med 1988 Mar;108(3):496. [https://doi.org/10.7326/0003-4819-107-4-451 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/2820289 PubMed]
+# '''RESPONSE:''' Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. [https://doi.org/10.1056/NEJMoa1409002 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25629741 PubMed] NCT01243944
-# '''SWOG S8232:''' Goodman GE, Crowley JJ, Blasko JC, Livingston RB, Beck TM, Demattia MD, Bukowski RM. Treatment of limited small-cell lung cancer with etoposide and cisplatin alternating with vincristine, doxorubicin, and cyclophosphamide versus concurrent etoposide, vincristine, doxorubicin, and cyclophosphamide and chest radiotherapy: a Southwest Oncology Group Study. J Clin Oncol. 1990 Jan;8(1):39-47. [https://doi.org/10.1200/JCO.1990.8.1.39 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2153194 PubMed]
+## '''Update:''' Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with Polycythemia Vera: 80 Week follow up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. Epub 2016 Apr 21. [http://www.haematologica.org/content/101/7/821 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004461/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27102499 PubMed]
-# Roth BJ, Johnson DH, Einhorn LH, Schacter LP, Cherng NC, Cohen HJ, Crawford J, Randolph JA, Goodlow JL, Broun GO, Omura GA, Greco FA; Southeastern Cancer Study Group. Randomized study of cyclophosphamide, doxorubicin, and vincristine versus etoposide and cisplatin versus alternation of these two regimens in extensive small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group. J Clin Oncol. 1992 Feb;10(2):282-91. [https://doi.org/10.1200/JCO.1992.10.2.282 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1310103 PubMed]
+## '''Update:''' Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. Epub 2020 Jan 23. [https://doi.org/10.1016/s2352-3026(19)30207-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31982039 PubMed]
-# '''JCOG9106:''' Furuse K, Fukuoka M, Nishiwaki Y, Kurita Y, Watanabe K, Noda K, Ariyoshi Y, Tamura T, Saijo N; [[Study_Groups#JCOG|JCOG]]. Phase III study of intensive weekly chemotherapy with recombinant human granulocyte colony-stimulating factor versus standard chemotherapy in extensive-disease small-cell lung cancer. J Clin Oncol. 1998 Jun;16(6):2126-32. [https://doi.org/10.1200/JCO.1998.16.6.2126 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9626212 PubMed]
+==Hydroxyurea monotherapy {{#subobject:82ab4d|Regimen=1}}==
-# Murray N, Livingston RB, Shepherd FA, James K, Zee B, Langleben A, Kraut M, Bearden J, Goodwin JW, Grafton C, Turrisi A, Walde D, Croft H, Osoba D, Ottaway J, Gandara D; National Cancer Institute of Canada Clinical Trials Group; [[Study_Groups#SWOG|SWOG]]. Randomized study of CODE versus alternating CAV/EP for extensive-stage small-cell lung cancer: an Intergroup Study of the National Cancer Institute of Canada Clinical Trials Group and the Southwest Oncology Group. J Clin Oncol. 1999 Aug;17(8):2300-8. [https://doi.org/10.1200/JCO.1999.17.8.2300 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10561291 PubMed]
-==CAVE {{#subobject:55aede|Regimen=1}}==
-CAVE: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine, '''<u>E</u>'''toposide
-<br>CAV-E: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine, '''<u>E</u>'''toposide
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:2a8dee|Variant=1}}===
+===Regimen {{#subobject:14ace8|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 556: / Line 179: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.1990.8.1.39 Goodman et al. 1990 (SWOG S8232)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ Vannucchi et al. 2015 (RESPONSE)]
-|1982-1984
+|2010-2013
-| style="background-color:#1a9851" |Phase 3 (C)
+|style="background-color:#1a9851"|Phase 3 (C)
-|[[#CAV.2FPE|CAV/PE]]
+|[[#Ruxolitinib_monotherapy|Ruxolitinib]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|style="background-color:#d73027"|Inferior disease control
-|-
-|[https://doi.org/10.1002/%28SICI)1097-0142%2819971215%2980%3A12%3C2222%3A%3AAID-CNCR2%3E3.0.CO%3B2-W Tummarello et al. 1997]
-|1990-1995
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#CAV-T_99|CAV-T]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS50%
 |-
 |}
-''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
+''The following is the approach recommended by Vannucchi in How I Treat (2014).''
-<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]]
+*[[Hydroxyurea (Hydrea)]] 500 mg PO twice per day, with titration based on the target hematocrit and hematologic toxicity
-*[[Doxorubicin (Adriamycin)]]
+'''Continued indefinitely'''
-*[[Vincristine (Oncovin)]]
-*[[Etoposide (Vepesid)]]
 </div></div>
 ===References===
-# '''SWOG S8232:''' Goodman GE, Crowley JJ, Blasko JC, Livingston RB, Beck TM, Demattia MD, Bukowski RM. Treatment of limited small-cell lung cancer with etoposide and cisplatin alternating with vincristine, doxorubicin, and cyclophosphamide versus concurrent etoposide, vincristine, doxorubicin, and cyclophosphamide and chest radiotherapy: a Southwest Oncology Group Study. J Clin Oncol. 1990 Jan;8(1):39-47. [https://doi.org/10.1200/JCO.1990.8.1.39 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2153194 PubMed]
+# '''RESPONSE:''' Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. [https://doi.org/10.1056/NEJMoa1409002 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25629741 PubMed] NCT01243944
-# Tummarello D, Mari D, Graziano F, Isidori P, Cetto G, Pasini F, Santo A, Cellerino R. A randomized, controlled phase III study of cyclophosphamide, doxorubicin, and vincristine with etoposide (CAV-E) or teniposide (CAV-T), followed by recombinant interferon-alpha maintenance therapy or observation, in small cell lung carcinoma patients with complete responses. Cancer. 1997 Dec 15;80(12):2222-9. [https://doi.org/10.1002/%28SICI)1097-0142%2819971215%2980%3A12%3C2222%3A%3AAID-CNCR2%3E3.0.CO%3B2-W link to original article] [https://pubmed.ncbi.nlm.nih.gov/9404698 PubMed]
+## '''Update:''' Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with Polycythemia Vera: 80 Week follow up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. Epub 2016 Apr 21. [http://www.haematologica.org/content/101/7/821 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004461/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27102499 PubMed]
-==CDE {{#subobject:344f89|Regimen=1}}==
+## '''Update:''' Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. Epub 2020 Jan 23. [https://doi.org/10.1016/s2352-3026(19)30207-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31982039 PubMed]
-CDE: '''<u>C</u>'''yclophosphamide, '''<u>D</u>'''oxorubicin, '''<u>E</u>'''toposide
+==Lenalidomide monotherapy {{#subobject:0dd38f|Regimen=1}}==
-<br>CAE: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>E</u>'''toposide
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:be62e9|Variant=1}}===
+===Regimen {{#subobject:b51df3|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 592: / Line 205: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://pubmed.ncbi.nlm.nih.gov/3020700 Bunn et al. 1986]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ Vannucchi et al. 2015 (RESPONSE)]
-|NR in abstract
+|2010-2013
-| style="background-color:#1a9851" |Randomized (E-switch-ic)
+|style="background-color:#1a9851"|Phase 3 (C)
-|[[#CAV_2|CAV]]
+|[[#Ruxolitinib_monotherapy|Ruxolitinib]]
-| style="background-color:#91cf60" |Seems to have superior OS
+|style="background-color:#d73027"|Inferior disease control
-|-
-|[https://doi.org/10.1016/0959-8049(96)00145-1 Postmus et al. 1996]
-|1988-1992
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#CDE.2FVIMP_99|CDE/VIMP]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-|-
-|[https://doi.org/10.1200/JCO.2002.02.069 Ardizzoni et al. 2002 (EORTC 08923)]
-|1994-1999
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#CDE|CDE]]; intensified
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-|-
-|[https://doi.org/10.1016/j.ejca.2007.07.029 de Jong et al. 2007 (CKVO-9802)]
-|1999-2005
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Carboplatin_.26_Paclitaxel_.28CP.29_99|CP]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+To be completed
-====Chemotherapy====
+====Targeted therapy====
-*[[Cyclophosphamide (Cytoxan)]]
+*[[Lenalidomide (Revlimid)]]
-*[[Doxorubicin (Adriamycin)]]
-*[[Etoposide (Vepesid)]]
 </div></div>
 ===References===
-# Bunn PA Jr, Greco FA, Einhorn L. Cyclophosphamide, doxorubicin, and etoposide as first-line therapy in the treatment of small-cell lung cancer. Semin Oncol. 1986 Sep;13(3 Suppl 3):45-53. [https://pubmed.ncbi.nlm.nih.gov/3020700 PubMed]
+# '''RESPONSE:''' Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. [https://doi.org/10.1056/NEJMoa1409002 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25629741 PubMed] NCT01243944
-# Postmus PE, Scagliotti G, Groen HJ, Gozzelino F, Burghouts JT, Curran D, Sahmoud T, Kirkpatrick A, Giaccone G, Splinter TA. Standard versus alternating non-cross-resistant chemotherapy in extensive small cell lung cancer: an EORTC phase III trial. Eur J Cancer. 1996 Aug;32A(9):1498-503. [https://doi.org/10.1016/0959-8049(96)00145-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8911108 PubMed]
+## '''Update:''' Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with Polycythemia Vera: 80 Week follow up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. Epub 2016 Apr 21. [http://www.haematologica.org/content/101/7/821 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004461/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27102499 PubMed]
-# '''EORTC 08923:''' Ardizzoni A, Tjan-Heijnen VC, Postmus PE, Buchholz E, Biesma B, Karnicka-Mlodkowska H, Dziadziuszko R, Burghouts J, Van Meerbeeck JP, Gans S, Legrand C, Debruyne C, Giaccone G, Manegold C; [[Study_Groups#EORTC|EORTC]]-Lung Cancer Group. Standard versus intensified chemotherapy with granulocyte colony-stimulating factor support in small-cell lung cancer: a prospective European Organisation for Research and Treatment of Cancer-Lung Cancer Group Phase III Trial-08923. J Clin Oncol. 2002 Oct 1;20(19):3947-55. [https://doi.org/10.1200/JCO.2002.02.069 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12351591 PubMed]
+## '''Update:''' Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. Epub 2020 Jan 23. [https://doi.org/10.1016/s2352-3026(19)30207-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31982039 PubMed]
-# '''CKVO-9802:''' de Jong WK, Groen HJ, Koolen MG, Biesma B, Willems LN, Kwa HB, van Bochove A, van Tinteren H, Smit EF. Phase III study of cyclophosphamide, doxorubicin, and etoposide compared with carboplatin and paclitaxel in patients with extensive disease small-cell lung cancer. Eur J Cancer. 2007 Nov;43(16):2345-50. Epub 2007 Sep 10. [https://doi.org/10.1016/j.ejca.2007.07.029 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17826977 PubMed] NCT00003696
+==Peginterferon alfa-2a monotherapy {{#subobject:2519d0|Regimen=1}}==
-==CEV (Cyclophosphamide/Epirubicin) {{#subobject:ec643a|Regimen=1}}==
-CEV: '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''pirubicin, '''<u>V</u>'''incristine
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:e4488b|Variant=1}}===
+===Regimen variant #1, 45 mcg starting dose {{#subobject:8615e6|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 20%"|Study
+!style="width: 33%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 33%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/jco.2002.12.111 Sundstrøm et al. 2002]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6839950/ Yacoub et al. 2019 (MPD-RC-111)]
-|1989-1994
+|2012-2015
-| style="background-color:#1a9851" |Phase 3 (C)
+|style="background-color:#91cf61"|Phase 2
-|[[Small_cell_lung_cancer#Cisplatin_.26_Etoposide_.28EP.29_2|Cisplatin & Etoposide]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
+====Immunotherapy====
-*[[Cyclophosphamide (Cytoxan)]]
+*[[Peginterferon alfa-2a (Pegasys)]] 45 mcg SC once per day on days 1, 8, 15, 22
-*[[Epirubicin (Ellence)]]
+**Titrated up by 45 mcg every month in the absence of toxicity to goal dose of 180 mcg
-*[[Vincristine (Oncovin)]]
+'''28-day cycles'''
-</div></div>
+</div></div><br>
-===References===
-# Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002 Dec 15;20(24):4665-72. [https://doi.org/10.1200/jco.2002.12.111 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12488411 PubMed]
-==CEV (Cyclophosphamide/Etoposide) {{#subobject:eu7r3a|Regimen=1}}==
-CEV: '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide, '''<u>V</u>'''incristine
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:yr328b|Variant=1}}===
+===Regimen variant #2, 90 mcg starting dose {{#subobject:868ce6|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 20%"|Study
+!style="width: 33%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 33%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1200/JCO.1989.7.4.450 Hong et al. 1989]
-|NR
-| style="background-color:#1a9851" |Randomized (E-esc)
-|1. [[#CAV_2|CAV]]<br>2. [[#Cyclophosphamide_.26_Vincristine_.28CV.29_88|CV]]
-| style="background-color:#1a9850" |Superior OS
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Etoposide (Vepesid)]]
-*[[Vincristine (Oncovin)]]
-</div></div>
-===References===
-# Hong WK, Nicaise C, Lawson R, Maroun JA, Comis R, Speer J, Luedke D, Hurtubise M, Lanzotti V, Goodlow J, Rozencweig M; Bristol Lung Cancer Study Group. Etoposide combined with cyclophosphamide plus vincristine compared with doxorubicin plus cyclophosphamide plus vincristine and with high-dose cyclophosphamide plus vincristine in the treatment of small-cell carcinoma of the lung: a randomized trial of the Bristol Lung Cancer Study Group. J Clin Oncol. 1989 Apr;7(4):450-6. [https://doi.org/10.1200/JCO.1989.7.4.450 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2538577 PubMed]
-==CEV (Carboplatin/Etoposide) {{#subobject:ec321a|Regimen=1}}==
-CEV: '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide, '''<u>V</u>'''incristine
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:e4488b|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://academic.oup.com/jnci/article/95/15/1118/2520358 Reck et al. 2003]
-|1998-1999
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#PCE|TEC]]
-| style="background-color:#fc8d59" |Seems to have inferior OS
 |-
-|}
+|[http://www.bloodjournal.org/content/112/8/3065.long Kiladjian et al. 2008 (PVN1)]
-<div class="toccolours" style="background-color:#b3e2cd">
+|2004-2005
-====Chemotherapy====
+|style="background-color:#91cf61"|Phase 2
-*[[Carboplatin (Paraplatin)]]
-*[[Etoposide (Vepesid)]]
-*[[Vincristine (Oncovin)]]
-</div></div>
-===References===
-# Reck M, von Pawel J, Macha HN, Kaukel E, Deppermann KM, Bonnet R, Ulm K, Hessler S, Gatzemeier U. Randomized phase III trial of paclitaxel, etoposide, and carboplatin versus carboplatin, etoposide, and vincristine in patients with small-cell lung cancer. J Natl Cancer Inst. 2003 Aug 6;95(15):1118-27. [https://academic.oup.com/jnci/article/95/15/1118/2520358 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12902441 PubMed]
-==Cisplatin & Etoposide (EP) & Pembrolizumab {{#subobject:eeja26|Regimen=1}}==
-EP & Pembrolizumab: '''<u>E</u>'''toposide, '''<u>P</u>'''latinol (Cisplatin), Pembrolizumab
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:3ci91m|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7474472/ Rudin et al. 2020 (KEYNOTE-604)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881362/ Quintás-Cardama et al. 2009 (MDACC DM03-0109)]
-|2017-2018
+|2005-2009
-|style="background-color:#1a9851" |Phase 3 (E-esc)
+|style="background-color:#91cf61"|Phase 2
-|1a. [[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]<br>1b. [[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]
-| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup><br>OS24: 22.5% vs 11.2%<br>(HR 0.80, 95% CI 0.64-0.98)
 |-
 |}
-''<sup>1</sup>This result did not meet the pre-specified threshold for statistical significance, and was the basis for withdrawal of the FDA indication.''
+''Quintás-Cardama et al. 2009 does not provide guidance on dose escalation or target dosing. Kiladjian et al. 2008 does not provide details on the dose escalation procedure.''
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Cisplatin (Platinol)]] as follows:
-**Cycles 1 to 4: 75 mg/m<sup>2</sup> IV once on day 1
-*[[Etoposide (Vepesid)]] as follows:
-**Cycles 1 to 4: 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
 ====Immunotherapy====
-*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
+*[[Peginterferon alfa-2a (Pegasys)]] 90 mcg SC once per day on days 1, 8, 15, 22
-'''21-day cycle for up to 35 cycles (2 years)'''
+**Titrated up every two weeks in the absence of toxicity to 135 mcg SC once per day on days 1, 8, 15, 22
+**In the absence of hematologic response, dose increased to 180 mcg SC once per day on days 1, 8, 15, 22
+====Supportive therapy====
+*[[Aspirin]] 100 mg PO once per day unless intolerant (Kiladjian et al. 2008)
+'''28-day cycles'''
 </div></div>
 ===References===
-# '''KEYNOTE-604:''' Rudin CM, Awad MM, Navarro A, Gottfried M, Peters S, Csőszi T, Cheema PK, Rodriguez-Abreu D, Wollner M, Yang JC, Mazieres J, Orlandi FJ, Luft A, Gümüş M, Kato T, Kalemkerian GP, Luo Y, Ebiana V, Pietanza MC, Kim HR; KEYNOTE-604 Investigators. Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study. J Clin Oncol. 2020 Jul 20;38(21):2369-2379. Epub 2020 May 29. [https://doi.org/10.1200/jco.20.00793 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7474472/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32468956/ PubMed] NCT03066778
+<!-- no pre-pub disclosed -->
-==Cyclophosphamide & Lomustine {{#subobject:ab365b|Regimen=1}}==
+# '''PVN1:''' Kiladjian JJ, Cassinat B, Chevret S, Turlure P, Cambier N, Roussel M, Bellucci S, Grandchamp B, Chomienne C, Fenaux P. Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera. Blood. 2008 Oct 15;112(8):3065-72. Epub 2008 Jul 23. [http://www.bloodjournal.org/content/112/8/3065.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18650451 PubMed] NCT00241241
+<!-- no pre-pub disclosed -->
+# '''MDACC DM03-0109:''' Quintás-Cardama A, Kantarjian H, Manshouri T, Luthra R, Estrov Z, Pierce S, Richie MA, Borthakur G, Konopleva M, Cortes J, Verstovsek S. Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera. J Clin Oncol. 2009 Nov 10;27(32):5418-24. Epub 2009 Oct 13. [https://doi.org/10.1200/jco.2009.23.6075 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881362/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19826111 PubMed] NCT00452023
+## '''Update:''' Quintás-Cardama A, Abdel-Wahab O, Manshouri T, Kilpivaara O, Cortes J, Roupie AL, Zhang SJ, Harris D, Estrov Z, Kantarjian H, Levine RL, Verstovsek S. Molecular analysis of patients with polycythemia vera or essential thrombocythemia receiving pegylated interferon α-2a. Blood. 2013 Aug 8;122(6):893-901. Epub 2013 Jun 19. [http://www.bloodjournal.org/content/122/6/893.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739035/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23782935 PubMed]
+## '''Update:''' Masarova L, Patel KP, Newberry KJ, Cortes J, Borthakur G, Konopleva M, Estrov Z, Kantarjian H, Verstovsek S. Pegylated interferon alfa-2a in patients with essential thrombocythaemia or polycythaemia vera: a post-hoc, median 83 month follow-up of an open-label, phase 2 trial. Lancet Haematol. 2017 Apr;4(4):e165-e175. Epub 2017 Mar 10. [https://doi.org/10.1016/S2352-3026(17)30030-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421384/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28291640 PubMed]
+# '''MPD-RC-111:''' Yacoub A, Mascarenhas J, Kosiorek H, Prchal JT, Berenzon D, Baer MR, Ritchie E, Silver RT, Kessler C, Winton E, Finazzi MC, Rambaldi A, Vannucchi AM, Leibowitz D, Rondelli D, Arcasoy MO, Catchatourian R, Vadakara J, Rosti V, Hexner E, Kremyanskaya M, Sandy L, Tripodi J, Najfeld V, Farnoud N, Papaemmanuil E, Salama M, Singer-Weinberg R, Rampal R, Goldberg JD, Barbui T, Mesa R, Dueck AC, Hoffman R. Pegylated interferon alfa-2a for polycythemia vera or essential thrombocythemia resistant or intolerant to hydroxyurea. Blood. 2019 Oct 31;134(18):1498-1509. [https://doi.org/10.1182/blood.2019000428 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6839950/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31515250 PubMed] NCT01259856
+==Pipobroman monotherapy {{#subobject:f9eb67|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:th1b8b|Variant=1}}===
+===Regimen {{#subobject:26b5d3|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 747: / Line 282: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1002/1097-0142(19820415)49:8%3C1544::aid-cncr2820490806%3E3.0.co;2-j Ettinger & Lagakos 1982]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ Vannucchi et al. 2015 (RESPONSE)]
-|1973-1977
+|2010-2013
-| style="background-color:#1a9851" |Phase 3 (C)
+|style="background-color:#1a9851"|Phase 3 (C)
-|[[#Cyclophosphamide.2C_Lomustine.2C_Procarbazine|Cyclophosphamide, Lomustine, Procarbazine]]
+|[[#Ruxolitinib_monotherapy|Ruxolitinib]]
-| style="background-color:#fc8d59" |Seems to have inferior ORR
+|style="background-color:#d73027"|Inferior disease control
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+To be completed for historical reference
 ====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]]
+*[[Pipobroman (Vercyte)]]
-*[[Lomustine (CCNU)]]
 </div></div>
 ===References===
-#Ettinger DS, Lagakos S; ECOG. Phase III study of CCNU, cyclophosphamide, adriamycin, vincristine, and VP-16 in small-cell carcinoma of the lung. Cancer. 1982 Apr 15;49(8):1544-54. [https://doi.org/10.1002/1097-0142(19820415)49:8%3C1544::aid-cncr2820490806%3E3.0.co;2-j link to original article] [https://pubmed.ncbi.nlm.nih.gov/6279269/ PubMed]
+# '''Review:''' Passamonti F, Lazzarino M. Treatment of polycythemia vera and essential thrombocythemia: the role of pipobroman. Leuk Lymphoma. 2003 Sep;44(9):1483-8. [http://www.tandfonline.com/doi/full/10.3109/10428190309178768 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14565648 PubMed]
-==Cyclophosphamide, Lomustine, Methotrexate {{#subobject:ab343a|Regimen=1}}==
+# '''RESPONSE:''' Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. [https://doi.org/10.1056/NEJMoa1409002 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25629741 PubMed] NCT01243944
+## '''Update:''' Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with Polycythemia Vera: 80 Week follow up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. Epub 2016 Apr 21. [http://www.haematologica.org/content/101/7/821 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004461/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27102499 PubMed]
+## '''Update:''' Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. Epub 2020 Jan 23. [https://doi.org/10.1016/s2352-3026(19)30207-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31982039 PubMed]
+==Ruxolitinib monotherapy {{#subobject:f35a21|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:e4338b|Variant=1}}===
+===Regimen {{#subobject:364cac|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 771: / Line 308: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://jamanetwork.com/journals/jama/fullarticle/364557 Cohen et al. 1979]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4231215/ Verstovsek et al. 2014 (INCB18424-256)]
-|1975-1977
+|2008-NR
-| style="background-color:#1a9851" |Phase 3 (C)
+|style="background-color:#91cf61"|Phase 2
-|Chemotherapy & Thymosin fraction V
+|style="background-color:#d3d3d3"|
-| style="background-color:#fc8d59" |Seems to have inferior OS
+|style="background-color:#d3d3d3"|
 |-
-|}
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ Vannucchi et al. 2015 (RESPONSE)]
-<div class="toccolours" style="background-color:#b3e2cd">
+|2010-2013
-====Chemotherapy====
+|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ooc)
-*[[Cyclophosphamide (Cytoxan)]]
+|Standard therapy
-*[[Lomustine (CCNU)]]
+|style="background-color:#1a9850"|Superior disease control
-*[[Methotrexate (MTX)]]
-</div></div>
-===References===
-# Cohen MH, Chretien PB, Ihde DC, Fossieck BE Jr, Makuch R, Bunn PA Jr, Johnston AV, Shackney SE, Matthews MJ, Lipson SD, Kenady DE, Minna JD. Thymosin fraction V and intensive combination chemotherapy: prolonging the survival of patients with small-cell lung cancer. JAMA. 1979 Apr 27;241(17):1813-5. [https://jamanetwork.com/journals/jama/fullarticle/364557 link to original article] [https://pubmed.ncbi.nlm.nih.gov/219267 PubMed]
-==Cyclophosphamide, Lomustine, Procarbazine {{#subobject:abug71|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:thg1tb|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1002/1097-0142(19820415)49:8%3C1544::aid-cncr2820490806%3E3.0.co;2-j Ettinger & Lagakos 1982]
+|[https://doi.org/10.1016/S1470-2045(16)30558-7 Passamonti et al. 2016 (RESPONSE-2)]
-|1973-1977
+|2014-2015
-| style="background-color:#1a9851" |Phase 3 (E-esc)
+|style="background-color:#1a9851"|Phase 3b (E-switch-ooc)
-|[[#Cyclophosphamide_.26_Lomustine|Cyclophosphamide & Lomustine]]
+|Standard therapy
-| style="background-color:#91cf60" |Seems to have superior ORR
+|style="background-color:#1a9850"|Superior disease control
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Lomustine (CCNU)]]
-*[[Procarbazine (Matulane)]]
-</div></div>
-===References===
-#Ettinger DS, Lagakos S; ECOG. Phase III study of CCNU, cyclophosphamide, adriamycin, vincristine, and VP-16 in small-cell carcinoma of the lung. Cancer. 1982 Apr 15;49(8):1544-54. [https://doi.org/10.1002/1097-0142(19820415)49:8%3C1544::aid-cncr2820490806%3E3.0.co;2-j link to original article] [https://pubmed.ncbi.nlm.nih.gov/6279269/ PubMed]
-==EVI {{#subobject:21fa55|Regimen=1}}==
-EVI: '''<u>E</u>'''pirubicin, '''<u>V</u>'''indesine, '''<u>I</u>'''fosfamide
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:2fc579|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363948/ Sculier et al. 2001]
-|rowspan=2|1993-2000
-|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
-|1. [[#EVI_.26_GM-CSF_99|EVI & GM-CSF]]; accelerated
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-|-
-|2. Accelerated EVI & antibiotics
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-|-
-|}
-''Not commonly used but was a comparator arm for at least one RCT; here for reference purposes only.''
-====Chemotherapy====
-*[[Epirubicin (Ellence)]]
-*[[Vindesine (Eldisine)]]
-*[[Ifosfamide (Ifex)]]
-</div></div>
-===References===
-# Sculier JP, Paesmans M, Lecomte J, Van Cutsem O, Lafitte JJ, Berghmans T, Koumakis G, Florin MC, Thiriaux J, Michel J, Giner V, Berchier MC, Mommen P, Ninane V, Klastersky J; European Lung Cancer Working Party. A three-arm phase III randomised trial assessing, in patients with extensive-disease small-cell lung cancer, accelerated chemotherapy with support of haematological growth factor or oral antibiotics. Br J Cancer. 2001 Nov 16;85(10):1444-51. [https://doi.org/10.1054/bjoc.2001.2114 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363948/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/11720426 PubMed]
-==ICE {{#subobject:f535c2|Regimen=1}}==
-ICE: '''<u>I</u>'''fosfamide, '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:b30a1b|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://academic.oup.com/jnci/article/97/9/666/2544232 Lorigan et al. 2005]
-|1994-2001
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Dose-dense_ICE.2C_then_auto_HSCT_99|Dose-dense ICE, then auto HSCT]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Ifosfamide (Ifex)]]
-*[[Carboplatin (Paraplatin)]]
-*[[Etoposide (Vepesid)]]
-</div></div>
-===References===
-# Lorigan P, Woll PJ, O'Brien ME, Ashcroft LF, Sampson MR, Thatcher N. Randomized phase III trial of dose-dense chemotherapy supported by whole-blood hematopoietic progenitors in better-prognosis small-cell lung cancer. J Natl Cancer Inst. 2005 May 4;97(9):666-74. Erratum in: J Natl Cancer Inst. 2005 Jun 15;97(12):941. [https://academic.oup.com/jnci/article/97/9/666/2544232 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15870437 PubMed]
-==ICE-V {{#subobject:f5jbc2|Regimen=1}}==
-ICE-V: '''<u>I</u>'''fosfamide, '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide, '''<u>V</u>'''incristine
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:tr4a1b|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1200/jco.2004.00.9969 Thatcher et al. 2005 (MRC LU21)]
-|NR in abstract
-| style="background-color:#1a9851" |Phase 3 (E-esc)
-|1. [[#CDE|CDE]]<br>2. [[Small_cell_lung_cancer#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]
-| style="background-color:#1a9850" |Superior OS<br>Median OS: 15.6 vs 11.6 mo<br>(HR 0.74, 95% CI 0.60-0.91)
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Ifosfamide (Ifex)]]
-*[[Carboplatin (Paraplatin)]]
-*[[Etoposide (Vepesid)]]
-*[[Vincristine (Oncovin)]]
-</div></div>
-===References===
-#'''MRC LU21:''' Thatcher N, Qian W, Clark PI, Hopwood P, Sambrook RJ, Owens R, Stephens RJ, Girling DJ. Ifosfamide, carboplatin, and etoposide with midcycle vincristine versus standard chemotherapy in patients with small-cell lung cancer and good performance status: clinical and quality-of-life results of the British Medical Research Council multicenter randomized LU21 trial. J Clin Oncol. 2005 Nov 20;23(33):8371-9. [https://doi.org/10.1200/jco.2004.00.9969 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16293867/ PubMed] NCT00002822
-==PCDE {{#subobject:b5f588|Regimen=1}}==
-PCDE: '''<u>P</u>'''latinol (Cisplatin), '''<u>C</u>'''yclophosphamide, Epi'''<u>D</u>'''oxorubicin (Epirubicin), '''<u>E</u>'''toposide
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:bc58e8|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1200/JCO.1997.15.5.2082 Pujol et al. 1997]
-|1991-1994
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#PCDE|PCDE]]; high-dose
-| style="background-color:#1a9850" |Superior OS
-|-
-|[https://academic.oup.com/jnci/article/93/4/300/2906465 Pujol et al. 2001 (FNCLCC 95012)]
-|1996-1999
-| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[Small_cell_lung_cancer#Cisplatin_.26_Etoposide_.28EP.29_2|EP]]
-| style="background-color:#1a9850" |Superior OS
-|-
-|[https://doi.org/10.1200/JCO.2007.11.8109 Pujol et al. 2007 (FNCLCC cleo04 IFCT 00-01)]
-|2000-2004
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#PCDE_.26_Thalidomide_99|PCDE & Thalidomide]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Cisplatin (Platinol)]]
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Epirubicin (Ellence)]]
-*[[Etoposide (Vepesid)]]
-</div></div>
-===References===
-# Pujol JL, Douillard JY, Rivière A, Quoix E, Lagrange JL, Berthaud P, Bardonnet-Comte M, Polin V, Gautier V, Milleron B, Chomy F, Chomy P, Spaeth D, Le Chevalier T. Dose-intensity of a four-drug chemotherapy regimen with or without recombinant human granulocyte-macrophage colony-stimulating factor in extensive-stage small-cell lung cancer: a multicenter randomized phase III study. J Clin Oncol. 1997 May;15(5):2082-9. [https://doi.org/10.1200/JCO.1997.15.5.2082 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9164221 PubMed]
-# '''FNCLCC 95012:''' Pujol JL, Daurès JP, Rivière A, Quoix E, Westeel V, Quantin X, Breton JL, Lemarié E, Poudenx M, Milleron B, Moro D, Debieuvre D, Le Chevalier T. Etoposide plus cisplatin with or without the combination of 4'-epidoxorubicin plus cyclophosphamide in treatment of extensive small-cell lung cancer: a French Federation of Cancer Institutes multicenter phase III randomized study. J Natl Cancer Inst. 2001 Feb 21;93(4):300-8. [https://academic.oup.com/jnci/article/93/4/300/2906465 link to original article]  [https://pubmed.ncbi.nlm.nih.gov/11181777 PubMed] NCT00003606
-# '''FNCLCC cleo04/IFCT 00-01:''' Pujol JL, Breton JL, Gervais R, Tanguy ML, Quoix E, David P, Janicot H, Westeel V, Gameroff S, Genève J, Maraninchi D. Phase III double-blind, placebo-controlled study of thalidomide in extensive-disease small-cell lung cancer after response to chemotherapy: an intergroup study FNCLCC cleo04 IFCT 00-01. J Clin Oncol. 2007 Sep 1;25(25):3945-51. [https://doi.org/10.1200/JCO.2007.11.8109 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17761978 PubMed]
-==PCE {{#subobject:8703fa|Regimen=1}}==
-PCE: '''<u>P</u>'''aclitaxel, '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide
-<br>TEC: '''<u>T</u>'''axol (Paclitaxel) '''<u>E</u>'''toposide), '''<u>C</u>'''arboplatin
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:b2c397|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://academic.oup.com/jnci/article/95/15/1118/2520358 Reck et al. 2003]
-|1998-1999
-| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[#CEV_.28Carboplatin.2FEtoposide.29|CEV]]
-| style="background-color:#91cf60" |Seems to have superior OS
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Paclitaxel (Taxol)]]
-*[[Carboplatin (Paraplatin)]]
-*[[Etoposide (Vepesid)]]
-</div></div>
-===References===
-# Reck M, von Pawel J, Macha HN, Kaukel E, Deppermann KM, Bonnet R, Ulm K, Hessler S, Gatzemeier U. Randomized phase III trial of paclitaxel, etoposide, and carboplatin versus carboplatin, etoposide, and vincristine in patients with small-cell lung cancer. J Natl Cancer Inst. 2003 Aug 6;95(15):1118-27. [https://academic.oup.com/jnci/article/95/15/1118/2520358 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12902441 PubMed]
-==VIP {{#subobject:8703fa|Regimen=1}}==
-VIP: '''<u>V</u>'''epesid (Etoposide), '''<u>I</u>'''fosfamide, '''<u>P</u>'''latinol (Cisplatin)
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:b2c397|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1200/JCO.1995.13.10.2594 Loehrer et al. 1995]
-|1989-1993
-| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[Small_cell_lung_cancer#Cisplatin_.26_Etoposide_.28EP.29_2|Cisplatin & Etoposide]]
-| style="background-color:#91cf60" |Seems to have superior OS
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 1 to 4
-*[[Ifosfamide (Ifex)]] 1200 mg/m<sup>2</sup> IV once per day on days 1 to 4
-*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 4
-'''21-day cycle for 4 cycles'''
-</div></div>
-===References===
-# Loehrer PJ Sr, Ansari R, Gonin R, Monaco F, Fisher W, Sandler A, Einhorn LH; Hoosier Oncology Group. Cisplatin plus etoposide with and without ifosfamide in extensive small-cell lung cancer: a Hoosier Oncology Group study. J Clin Oncol. 1995 Oct;13(10):2594-9. [https://doi.org/10.1200/JCO.1995.13.10.2594 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/7595712 PubMed]
-==VMV-VAC {{#subobject:240cc3|Regimen=1}}==
-VMV-VAC: '''<u>V</u>'''incristine, '''<u>M</u>'''ethotrexate, '''<u>V</u>'''P-16 (Etoposide), '''<u>V</u>'''P-16 (Etoposide),  '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:5dd088|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1200/JCO.1984.2.6.585 Livingston et al. 1984 (SWOG S7828)]
-|1978-1980
-| style="background-color:#1a9851" |Phase 3 (E-esc)
-|1. [[#CAV_2|VAC]]<br>2. [[#VMV_88|VMV]]
-| style="background-color:#ffffbf" |Did not meet endpoint of OS
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''There were several doses evaluated in INCB18424-256; the median total daily dose was 21.7 mg corresponding to approximately 10 mg PO twice per day. The most common comparator in RESPONSE and RESPONSE-2 was [[#Hydroxyurea_monotherapy_2|hydroxyurea]].''
-====Chemotherapy====
+====Targeted therapy====
-*[[Vincristine (Oncovin)]]
+*[[Ruxolitinib (Jakafi)]] 10 mg PO twice per day
-*[[Methotrexate (MTX)]]
+'''Continued indefinitely'''
-*[[Etoposide (Vepesid)]]
-*[[Doxorubicin (Adriamycin)]]
-*[[Cyclophosphamide (Cytoxan)]]
 </div></div>
 ===References===
-# '''SWOG S7828:''' Livingston RB, Mira JG, Chen TT, McGavran M, Costanzi JJ, Samson M. Combined modality treatment of extensive small cell lung cancer: a Southwest Oncology Group study. J Clin Oncol. 1984 Jun;2(6):585-90. [https://doi.org/10.1200/JCO.1984.2.6.585 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6327927 PubMed]
+# '''INCB18424-256:''' Verstovsek S, Passamonti F, Rambaldi A, Barosi G, Rosen PJ, Rumi E, Gattoni E, Pieri L, Guglielmelli P, Elena C, He S, Contel N, Mookerjee B, Sandor V, Cazzola M, Kantarjian HM, Barbui T, Vannucchi AM. A phase 2 study of ruxolitinib, an oral JAK1 and JAK2 Inhibitor, in patients with advanced polycythemia vera who are refractory or intolerant to hydroxyurea. Cancer. 2014 Feb 15;120(4):513-20. [https://doi.org/10.1002/cncr.28441 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4231215/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24258498 PubMed] content property of [http://hemonc.org HemOnc.org] NCT00726232
-=Relapsed or refractory disease=
+# '''RESPONSE:''' Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. [https://doi.org/10.1056/NEJMoa1409002 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25629741 PubMed] NCT01243944
-==CAV {{#subobject:d3d3e|Regimen=1}}==
+<!-- ## '''Update: Abstract:''' Jean-Jacques Kiladjian, Alessandro M. Vannucchi, Martin Griesshammer, Tamas Masszi, Simon Durrant, Francesco Passamonti, Claire N. Harrison, Fabrizio Pane, Pierre Zachee, Keita Kirito, Mario Cazzola, Carlos Besses, Igor Blau, Ruben Mesa, Mark M. Jones, Shui He, Huiling Zhen, Jingjin Li, Nathalie Francillard, Dany Habr, Srdan Verstovsek. Ruxolitinib versus best available therapy in patients with polycythemia vera: 80-week follow-up from the response trial. EHA 2015 Abstract: S447 [http://learningcenter.ehaweb.org/eha/2015/20th/103108/jean-jacques.kiladjian.ruxolitinib.versus.best.available.therapy.in.patients.html?f=l5449p16m3 link to abstract] -->
-CAV: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine
+## '''Update:''' Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with Polycythemia Vera: 80 Week follow up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. Epub 2016 Apr 21. [http://www.haematologica.org/content/101/7/821 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004461/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27102499 PubMed]
+## '''Update:''' Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. Epub 2020 Jan 23. [https://doi.org/10.1016/s2352-3026(19)30207-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31982039 PubMed]
+# '''RESPONSE-2:''' Passamonti F, Griesshammer M, Palandri F, Egyed M, Benevolo G, Devos T, Callum J, Vannucchi AM, Sivgin S, Bensasson C, Khan M, Mounedji N, Saydam G. Ruxolitinib for the treatment of inadequately controlled polycythaemia vera without splenomegaly (RESPONSE-2): a randomised, open-label, phase 3b study. Lancet Oncol. 2017 Jan;18(1):88-99. Epub 2016 Dec 2. [https://doi.org/10.1016/S1470-2045(16)30558-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27916398 PubMed] NCT02038036
+##'''Update:''' Passamonti F, Palandri F, Saydam G, Callum J, Devos T, Guglielmelli P, Vannucchi AM, Zor E, Zuurman M, Gilotti G, Zhang Y, Griesshammer M. Ruxolitinib versus best available therapy in inadequately controlled polycythaemia vera without splenomegaly (RESPONSE-2): 5-year follow up of a randomised, phase 3b study. Lancet Haematol. 2022 Jul;9(7):e480-e492. Epub 2022 May 18. [https://doi.org/10.1016/s2352-3026(22)00102-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35597252/ PubMed]
+==Thalidomide monotherapy {{#subobject:cfd2c6|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, no capping {{#subobject:1ugcbf|Variant=1}}===
+===Regimen {{#subobject:63b4bf|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 1,028: / Line 350: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1016/s2213-2600(22)00309-5 Aix et al. 2022 (ATLANTIS)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ Vannucchi et al. 2015 (RESPONSE)]
-|2016-2018
+|2010-2013
-| style="background-color:#1a9851" |Phase 3 (C)
+|style="background-color:#1a9851"|Phase 3 (C)
-|[[#Doxorubicin_.26_Lurbinectedin|Doxorubicin & Lurbinectedin]]
+|[[#Ruxolitinib_monotherapy|Ruxolitinib]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|style="background-color:#d73027"|Inferior disease control
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+To be completed
-====Chemotherapy====
+====Targeted therapy====
-*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1
+*[[Thalidomide (Thalomid)]]
-*[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> IV once on day 1
-*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
-'''21-day cycles'''
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, capped {{#subobject:83cdbf|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1200/jco.1999.17.2.658 von Pawel et al. 1999]
-|NR
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[Small_cell_lung_cancer#Topotecan_monotherapy|Topotecan]]
-| style="background-color:#ffffbf" |Did not meet primary endpoints of ORR/DOR
-|-
-|}
-''von Pawel et al. 1999 does not clearly state the duration of each cycle, but 21 days is used in other CAV regimens, and there was no information in the paper that contradicted this.''
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> (maximum dose of 2000 mg) (route not specified) once on day 1
-*[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> (maximum dose of 100 mg) IV once on day 1
-*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
-====Supportive therapy====
-*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] use per physician discretion
-'''21-day cycle for up to 6 cycles beyond maximal response'''
-''Patients with stable disease after 4 cycles could have treatment discontinued at physician discretion.''
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #3 {{#subobject:531cce|Variant=1}}===
-{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://doi.org/10.1200/jco.1994.12.10.2022 Ihde et al. 1994]
-|1983-1991
-| style="background-color:#91cf61" |Non-randomized portion of RCT
-|-
-|}
-''Note: Ihde et al. 1994 did not specifically say that the three medications were all given on day 1, but this is assumed to be the case based on other CAV regimens.''
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*[[#Cisplatin_.26_Etoposide_.28EP.29_2|EP]]; standard-dose versus [[#Cisplatin_.26_Etoposide_.28EP.29|EP]]; high-dose, with progression
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1
-*[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> IV once on day 1
-*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
-'''21-day cycle for 4 cycles'''
-</div></div>
-===References===
-# Ihde DC, Mulshine JL, Kramer BS, Steinberg SM, Linnoila RI, Gazdar AF, Edison M, Phelps RM, Lesar M, Phares JC, Grayson J, Minna JD, Johnson BE. Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer. J Clin Oncol. 1994 Oct;12(10):2022-34. [https://doi.org/10.1200/jco.1994.12.10.2022 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/7931470 PubMed]
-# von Pawel J, Schiller JH, Shepherd FA, Fields SZ, Kleisbauer JP, Chrysson NG, Stewart DJ, Clark PI, Palmer MC, Depierre A, Carmichael J, Krebs JB, Ross G, Lane SR, Gralla R. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol. 1999 Feb;17(2):658-67. [https://doi.org/10.1200/jco.1999.17.2.658 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10080612 PubMed]
-#'''ATLANTIS:''' Aix SP, Ciuleanu TE, Navarro A, Cousin S, Bonanno L, Smit EF, Chiappori A, Olmedo ME, Horvath I, Grohé C, Farago AF, López-Vilariño JA, Cullell-Young M, Nieto A, Vasco N, Gómez J, Kahatt C, Zeaiter A, Carcereny E, Roubec J, Syrigos K, Lo G, Barneto I, Pope A, Sánchez A, Kattan J, Zarogoulidis K, Waller CF, Bischoff H, Juan-Vidal O, Reinmuth N, Dómine M, Paz-Ares L. Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial. Lancet Respir Med. 2023 Jan;11(1):74-86. Epub 2022 Oct 14. [https://doi.org/10.1016/s2213-2600(22)00309-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/36252599/ PubMed] NCT02566993
-==CDE {{#subobject:fd0ec6|Regimen=1}}==
-CDE: '''<u>C</u>'''yclophosphamide, '''<u>D</u>'''oxorubicin, '''<u>E</u>'''toposide
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:65860f|Variant=1}}===
-{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://doi.org/10.1016/0277-5379(87)90128-3 Postmus et al. 1987]
-|NR
-| style="background-color:#91cf61" |Phase 2
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1
-*[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> IV once on day 1
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
-'''21-day cycle for 5 cycles'''
-</div></div>
-===References===
-# Postmus PE, Berendsen HH, van Zandwijk N, Splinter TA, Burghouts JT, Bakker W. Retreatment with the induction regimen in small cell lung cancer relapsing after an initial response to short term chemotherapy. Eur J Cancer Clin Oncol. 1987 Sep;23(9):1409-11. [https://doi.org/10.1016/0277-5379(87)90128-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2824211 PubMed]
-==Ipilimumab & Nivolumab {{#subobject:7bc416|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1 {{#subobject:aa43c1|Variant=1}}===
-{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://doi.org/10.1016/S1470-2045(16)30098-5 Antonia et al. 2016 (CheckMate 032)]
-|2013-2015
-| style="background-color:#91cf61" |Phase 1/2 (RT)
-|-
-|}
-''Note: it is unclear which schedule of ipilimumab & nivolumab is preferred based on the abstract.''
-<div class="toccolours" style="background-color:#b3e2cd">
-====Immunotherapy====
-*[[Ipilimumab (Yervoy)]] as follows:
-**Cycles 1 to 4: 1 mg/kg IV once on day 1
-*[[Nivolumab (Opdivo)]] 3 mg/kg IV once on day 1
-'''21-day cycle for 4 cycles, then 14-day cycles'''
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2 {{#subobject:b6a1ee|Variant=1}}===
-{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://doi.org/10.1016/S1470-2045(16)30098-5 Antonia et al. 2016 (CheckMate 032)]
-|2013-2015
-| style="background-color:#91cf61" |Phase 1/2 (RT)
-|-
-|}
-''Note: it is unclear which schedule of ipilimumab & nivolumab is preferred based on the abstract.''
-<div class="toccolours" style="background-color:#b3e2cd">
-====Immunotherapy====
-*[[Ipilimumab (Yervoy)]] as follows:
-**Cycles 1 to 4: 3 mg/kg IV once on day 1
-*[[Nivolumab (Opdivo)]] as follows:
-**Cycles 1 to 4: 1 mg/kg IV once on day 1
-**Cycle 5 onwards: 3 mg/kg IV once on day 1
-'''21-day cycle for 4 cycles, then 14-day cycles'''
-</div></div>
-===References===
-# '''CheckMate 032:''' Antonia SJ, López-Martin JA, Bendell J, Ott PA, Taylor M, Eder JP, Jäger D, Pietanza MC, Le DT, de Braud F, Morse MA, Ascierto PA, Horn L, Amin A, Pillai RN, Evans J, Chau I, Bono P, Atmaca A, Sharma P, Harbison CT, Lin CS, Christensen O, Calvo E. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol. 2016 Jul;17(7):883-95. Epub 2016 Jun 4. [https://doi.org/10.1016/S1470-2045(16)30098-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27269741 PubMed] NCT01928394
-##'''Update:''' Ready NE, Ott PA, Hellmann MD, Zugazagoitia J, Hann CL, de Braud F, Antonia SJ, Ascierto PA, Moreno V, Atmaca A, Salvagni S, Taylor M, Amin A, Camidge DR, Horn L, Calvo E, Li A, Lin WH, Callahan MK, Spigel DR. Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Recurrent Small Cell Lung Cancer: Results From the CheckMate 032 Randomized Cohort. J Thorac Oncol. 2020 Mar;15(3):426-435. Epub 2019 Oct 17. [https://doi.org/10.1016/j.jtho.2019.10.004 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31629915/ PubMed]
-==Nivolumab monotherapy {{#subobject:67a13c|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, weight-based {{#subobject:5a9324|Variant=1}}===
-{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://doi.org/10.1016/S1470-2045(16)30098-5 Antonia et al. 2016 (CheckMate 032)]
-|2013-2015
-| style="background-color:#91cf61" |Phase 1/2 (RT)
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Immunotherapy====
-*[[Nivolumab (Opdivo)]] 3 mg/kg IV once on day 1
-'''14-day cycles'''
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, flat dose {{#subobject:5a8guac|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1016/j.annonc.2021.01.071 Spigel et al. 2021 (CheckMate 331)]
-|2015-2017
-| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
-|1. [[Small_cell_lung_cancer#Amrubicin_monotherapy|Amrubicin]]<br>2. [[Small_cell_lung_cancer#Topotecan_monotherapy|Topotecan]]
-| style="background-color:#d9ef8b" |Might have superior OS<br>Median OS: 7.5 vs 8.4 mo<br>(HR 0.86, 95% CI 0.72-1.04)
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Immunotherapy====
-*[[Nivolumab (Opdivo)]] 240 mg IV over 30 minutes once on day 1
-'''14-day cycles'''
-</div></div>
-===References===
-# '''CheckMate 032:''' Antonia SJ, López-Martin JA, Bendell J, Ott PA, Taylor M, Eder JP, Jäger D, Pietanza MC, Le DT, de Braud F, Morse MA, Ascierto PA, Horn L, Amin A, Pillai RN, Evans J, Chau I, Bono P, Atmaca A, Sharma P, Harbison CT, Lin CS, Christensen O, Calvo E. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol. 2016 Jul;17(7):883-95. Epub 2016 Jun 4. [https://doi.org/10.1016/S1470-2045(16)30098-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27269741 PubMed] NCT01928394
-##'''Update:''' Ready NE, Ott PA, Hellmann MD, Zugazagoitia J, Hann CL, de Braud F, Antonia SJ, Ascierto PA, Moreno V, Atmaca A, Salvagni S, Taylor M, Amin A, Camidge DR, Horn L, Calvo E, Li A, Lin WH, Callahan MK, Spigel DR. Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Recurrent Small Cell Lung Cancer: Results From the CheckMate 032 Randomized Cohort. J Thorac Oncol. 2020 Mar;15(3):426-435. Epub 2019 Oct 17. [https://doi.org/10.1016/j.jtho.2019.10.004 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31629915/ PubMed]
-# '''CheckMate 331:''' Spigel DR, Vicente D, Ciuleanu TE, Gettinger S, Peters S, Horn L, Audigier-Valette C, Pardo Aranda N, Juan-Vidal O, Cheng Y, Zhang H, Shi M, Luft A, Wolf J, Antonia S, Nakagawa K, Fairchild J, Baudelet C, Pandya D, Doshi P, Chang H, Reck M. Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331. Ann Oncol. 2021 May;32(5):631-641. Epub 2021 Feb 1. [https://doi.org/10.1016/j.annonc.2021.01.071 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33539946/ PubMed] NCT02481830
-==Pembrolizumab monotherapy {{#subobject:bc1cf4|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 10 mg/kg q2wk {{#subobject:96a1cg|Variant=1}}===
-{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://doi.org/10.1200/JCO.2017.72.5069 Ott et al. 2017c (KEYNOTE-028)]
-|2014-2015
-| style="background-color:#91cf61" |Phase 1b (RT)
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Immunotherapy====
-*[[Pembrolizumab (Keytruda)]] 10 mg/kg IV once on day 1
-'''14-day cycle for up to 52 cycles (2 years)'''
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, 200 mg q3wk {{#subobject:ac7fd1|Variant=1}}===
-{| class="wikitable" style="color:white; background-color:#404040"
-|<small>'''FDA-recommended dose'''</small>
-|-
-|}
-{| class="wikitable" style="width: 40%; text-align:center;"
-! style="width: 50%" |Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://www.clinicaltrials.gov/ct2/show/NCT02628067 Awaiting publication (KEYNOTE-158)]
-| style="background-color:#91cf61" |Phase 2
-|-
-|}
-''Note: this arm of KEYNOTE-158 has not been published yet, to our knowledge.''
-<div class="toccolours" style="background-color:#b3e2cd">
-====Immunotherapy====
-*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
-'''21-day cycle for up to 35 cycles (2 years)'''
 </div></div>
 ===References===
-# '''KEYNOTE-028:''' Ott PA, Elez E, Hiret S, Kim DW, Morosky A, Saraf S, Piperdi B, Mehnert JM. Pembrolizumab in patients With extensive-stage small-cell lung cancer: results from the phase Ib KEYNOTE-028 study. J Clin Oncol. 2017 Dec 1;35(34):3823-3829. Epub 2017 Aug 16. [https://doi.org/10.1200/JCO.2017.72.5069 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28813164 PubMed] NCT02054806
+# '''RESPONSE:''' Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. [https://doi.org/10.1056/NEJMoa1409002 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25629741 PubMed] NCT01243944
-# '''KEYNOTE-158:''' NCT02628067
+## '''Update:''' Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with Polycythemia Vera: 80 Week follow up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. Epub 2016 Apr 21. [http://www.haematologica.org/content/101/7/821 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004461/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27102499 PubMed]
-[[Category:Small cell lung cancer regimens]]
+## '''Update:''' Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. Epub 2020 Jan 23. [https://doi.org/10.1016/s2352-3026(19)30207-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31982039 PubMed]
-[[Category:Historical regimens]]
+=Response criteria=
+==ELN==
+*'''2009:''' [http://www.bloodjournal.org/content/113/20/4829.long Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference]
+[[Category:Polycythemia vera regimens]]
 [[Category:Disease-specific pages]]
-[[Category:Lung cancers]]
+[[Category:Myeloproliferative neoplasms]]

Difference between revisions of "Staging page"

Revision as of 12:53, 31 December 2022

Guidelines

ELN

ESMO

"How I Treat"

NCCN

First-line therapy

Aspirin monotherapy

Regimen

Anticoagulation

References

Hydroxyurea monotherapy

Regimen

Chemotherapy

Supportive therapy

References

Placebo

Regimen

References

Ropeginterferon alfa-2b monotherapy

Regimen

Immunotherapy

References

Relapsed, refractory, or intolerant

Anagrelide monotherapy

Regimen

Anticoagulation

References

Hydroxyurea monotherapy

Regimen

Chemotherapy

References

Lenalidomide monotherapy

Regimen

Targeted therapy

References

Peginterferon alfa-2a monotherapy

Regimen variant #1, 45 mcg starting dose

Immunotherapy

Regimen variant #2, 90 mcg starting dose

Immunotherapy

Supportive therapy

References

Pipobroman monotherapy

Regimen

Chemotherapy

References

Ruxolitinib monotherapy

Regimen

Targeted therapy

References

Thalidomide monotherapy

Regimen

Targeted therapy

References

Response criteria

ELN

Navigation menu

Search