Difference between revisions of "Peripheral T-cell lymphoma"
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# O'Connor OA, Horwitz S, Masszi T, Van Hoof A, Brown P, Doorduijn J, Hess G, Jurczak W, Knoblauch P, Chawla S, Bhat G, Choi MR, Walewski J, Savage K, Foss F, Allen LF, Shustov A. Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study. J Clin Oncol. 2015 Aug 10;33(23):2492-9. Epub 2015 Jun 22. [http://jco.ascopubs.org/content/33/23/2492.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/26101246 PubMed] | # O'Connor OA, Horwitz S, Masszi T, Van Hoof A, Brown P, Doorduijn J, Hess G, Jurczak W, Knoblauch P, Chawla S, Bhat G, Choi MR, Walewski J, Savage K, Foss F, Allen LF, Shustov A. Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study. J Clin Oncol. 2015 Aug 10;33(23):2492-9. Epub 2015 Jun 22. [http://jco.ascopubs.org/content/33/23/2492.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/26101246 PubMed] | ||
− | ==Bendamustine ( | + | ==Bendamustine (Bendeka) {{#subobject:47c984|Regimen=1}}== |
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− | *[[Bendamustine ( | + | *[[Bendamustine (Bendeka)]] 120 mg/m2 IV over 30 to 60 minutes once per day on days 1 & 2 |
'''3-week cycle x 6 cycles''' | '''3-week cycle x 6 cycles''' |
Revision as of 21:13, 2 April 2016
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30 regimens on this page
37 variants on this page
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Untreated, randomized data
CHOP
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CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
Synonyms: CHOP-21, ACOP, CAVP, COPA, VACP, VCAP
Structured Concept: C9549 (NCI-T), C0055598 (NCI-MT/UMLS)
Regimen
Study | Evidence | Comparator |
Simon et al. 2010 (GOELAMS LTP95) | Phase III | VIP-rABVD |
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose per cycle: 2 mg) IV once on day 1
- Prednisone (Sterapred) 100 mg/m2 PO once per day on days 1 to 5
21-day cycle x 8 cycles
Radiation therapy for initial bulky disease
"Initial bulky disease": patients with "diameter = 5 cm"
- Radiation therapy, 40 Gy at 1.8 Gy/day to the involved field
References
- Simon A, Peoch M, Casassus P, Deconinck E, Colombat P, Desablens B, Tournilhac O, Eghbali H, Foussard C, Jaubert J, Vilque JP, Rossi JF, Lucas V, Delwail V, Thyss A, Maloisel F, Milpied N, le Gouill S, Lamy T, Gressin R. Upfront VIP-reinforced-ABVD (VIP-rABVD) is not superior to CHOP/21 in newly diagnosed peripheral T cell lymphoma. Results of the randomized phase III trial GOELAMS-LTP95. Br J Haematol. 2010 Oct;151(2):159-66. Epub 2010 Aug 25. link to original article contains verified protocol PubMed
Untreated, non-randomized or retrospective data
CHOEP-14 -> upfront autologous SCT
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CHOEP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Etoposide, Prednisone
Regimen
Study | Evidence |
d'Amore et al. 2012 (NLG-T-01) | Phase II |
Etoposide is omitted for patients older than 60 years of age.
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
- Prednisone (Sterapred) 50 mg PO BID on days 1 to 5
14-day cycle x 6 cycles
If patients in PR or CR after three cycles, stem cells are mobilized off of cycles 5 and 6, followed by:
References
- d'Amore F, Relander T, Lauritzsen GF, Jantunen E, Hagberg H, Anderson H, Holte H, Österborg A, Merup M, Brown P, Kuittinen O, Erlanson M, Østenstad B, Fagerli UM, Gadeberg OV, Sundström C, Delabie J, Ralfkiaer E, Vornanen M, Toldbod HE. Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01. J Clin Oncol. 2012 Sep 1;30(25):3093-9. Epub 2012 Jul 30. link to original article contains verified protocol PubMed
CHOP
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CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
Synonyms: CHOP-21, ACOP, CAVP, COPA, VACP, VCAP
Structured Concept: C9549 (NCI-T), C0055598 (NCI-MT/UMLS)
Regimen
Study | Evidence |
Reimer et al. 2004 | Phase II |
This study reports using CHOP but doesn't specify the doses; below is a fairly standard CHOP regimen:
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
21-day cycle x 4 to 6 cycles
If CR obtained after 4 cycles or at least a PR after 6 cycles, patients proceeded to autologous stem cell transplant.
References
- Reimer P, Schertlin T, Rüdiger T, Geissinger E, Roth S, Kunzmann V, Weissinger F, Nerl C, Schmitz N, Müller-Hermelink HK, Wilhelm M. Myeloablative radiochemotherapy followed by autologous peripheral blood stem cell transplantation as first-line therapy in peripheral T-cell lymphomas: first results of a prospective multicenter study. Hematol J. 2004;5(4):304-11. PubMed
- Update: Reimer P, Rüdiger T, Geissinger E, Weissinger F, Nerl C, Schmitz N, Engert A, Einsele H, Müller-Hermelink HK, Wilhelm M. Autologous stem-cell transplantation as first-line therapy in peripheral T-cell lymphomas: results of a prospective multicenter study. J Clin Oncol. 2009 Jan 1;27(1):106-13. Epub 2008 Nov 24. link to original article PubMed
- Meta-analysis: Abouyabis AN, Shenoy PJ, Sinha R, Flowers CR, Lechowicz MJ. A Systematic Review and Meta-Analysis of Front-line Anthracycline-Based Chemotherapy Regimens for Peripheral T-Cell Lymphoma. ISRN Hematol. 2011;2011:623924. Epub 2011 Jun 16. link to original article PubMed
CHOP-AL -> HyperCHidam
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CHOP-AL: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone, ALemtuzumab
HyperCHidam: Hyperfractionated Cyclophosphamide, Hiigh-dose ara-c (Cytarabine) & methotrexate
Regimen
Study | Evidence |
Corradini et al. 2014 | Phase II |
These are the details for "Clin A" which was the regimen used for patients younger than 60.
CHOP portion
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
- Alemtuzumab (Campath) as follows
- 3 mg IV once on day -2 before cycle 1
- 10 mg IV once on day -1 before cycle 1
- 20 mg IV once on day 0 before cycle 1
- 30 mg IV once on day 0 before cycle 2 (= day 21 of cycle 1)
21-day cycle x 2 cycles, followed by:
HyperCHidam
- Methotrexate (MTX) 1.6 g/m2 IV as a continuous infusion on day 1
- Cyclophosphamide (Cytoxan) 300 mg/m2 IV q12h for 3 days (start day not specified)
- Cytarabine (Cytosar) 2 g/m2 IV q12h for 3 days (start day not specified)
Supportive medications:
- Granulocyte-colony stimulating factor 5 mcg/kg once per day was given from day +5 (stop date not specified)
Duration not specified x 2 cycles
Responders (PR/CR) proceeded to allogeneic stem cell transplant.
References
- Corradini P, Vitolo U, Rambaldi A, Miceli R, Patriarca F, Gallamini A, Olivieri A, Benedetti F, Todeschini G, Rossi G, Salvi F, Bruno B, Baldini L, Ferreri A, Patti C, Tarella C, Pileri S, Dodero A. Intensified chemo-immunotherapy with or without stem cell transplantation in newly diagnosed patients with peripheral T-cell lymphoma. Leukemia. 2014 Sep;28(9):1885-91. Epub 2014 Feb 20. link to original article contains verified protocol PubMed
DD-CHOP
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DD-CHOP: Denileukin, Diftitox, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
Regimen
Study | Evidence |
Foss et al. 2013 (CONCEPT) | Phase II |
- Denileukin diftitox (Ontak) 18 mcg/kg IV over 60 minutes once per day on days 1 & 2
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 3
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 3
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 3
- Prednisone (Sterapred) 100 mg PO once per day on days 3 to 7
Supportive medications:
- Dexamethasone (Decadron) 4 to 8 mg IV/PO prior to Denileukin diftitox (Ontak)
- Acetaminophen (Tylenol) 650 mg PO prior to Denileukin diftitox (Ontak)
- Diphenhydramine (Benadryl) 25 mg IV prior to Denileukin diftitox (Ontak)
- Normal saline 250 to 500 cc before and after each Denileukin diftitox (Ontak) infusion
- Antiemetics "per institutional standard"
- G-CSF support beginning on day 4
21-day cycles x 6 to 8 cycles
References
- Foss FM, Sjak-Shie N, Goy A, Jacobsen E, Advani R, Smith MR, Komrokji R, Pendergrass K, Bolejack V. A multicenter phase II trial to determine the safety and efficacy of combination therapy with denileukin diftitox and cyclophosphamide, doxorubicin, vincristine and prednisone in untreated peripheral T-cell lymphoma: the CONCEPT study. Leuk Lymphoma. 2013 Jul;54(7):1373-9. Epub 2013 Jan 29. link to original article contains verified protocol PubMed
Consolidation and/or maintenance after upfront therapy
Allogeneic stem cell transplant
To be completed. Usually reserved for younger and very fit individuals. See details about preparative regimens.
Regimen
Study | Evidence |
Corradini et al. 2014 | Phase II |
Treatment preceded by CHOP-AL x 2, HyperCHidam x 2.
Details to be completed.
References
- Corradini P, Tarella C, Olivieri A, Gianni AM, Voena C, Zallio F, Ladetto M, Falda M, Lucesole M, Dodero A, Ciceri F, Benedetti F, Rambaldi A, Sajeva MR, Tresoldi M, Pileri A, Bordignon C, Bregni M. Reduced-intensity conditioning followed by allografting of hematopoietic cells can produce clinical and molecular remissions in patients with poor-risk hematologic malignancies. Blood. 2002 Jan 1;99(1):75-82. link to original article PubMed
- Corradini P, Vitolo U, Rambaldi A, Miceli R, Patriarca F, Gallamini A, Olivieri A, Benedetti F, Todeschini G, Rossi G, Salvi F, Bruno B, Baldini L, Ferreri A, Patti C, Tarella C, Pileri S, Dodero A. Intensified chemo-immunotherapy with or without stem cell transplantation in newly diagnosed patients with peripheral T-cell lymphoma. Leukemia. 2014 Sep;28(9):1885-91. Epub 2014 Feb 20. link to original article contains verified protocol PubMed
Autologous stem cell transplant
To be completed. See details about preparative regimens.
Regimen
Study | Evidence |
Reimer et al. 2004 | Phase II |
Treatment preceded by CHOP x 4 to 6 cycles.
Patients received either DexaBEAM or ESHAP followed by autologous stem cell transplant. Details are not available with regards to the conditioning regimens.
References
- Reimer P, Schertlin T, Rüdiger T, Geissinger E, Roth S, Kunzmann V, Weissinger F, Nerl C, Schmitz N, Müller-Hermelink HK, Wilhelm M. Myeloablative radiochemotherapy followed by autologous peripheral blood stem cell transplantation as first-line therapy in peripheral T-cell lymphomas: first results of a prospective multicenter study. Hematol J. 2004;5(4):304-11. PubMed
- Update: Reimer P, Rüdiger T, Geissinger E, Weissinger F, Nerl C, Schmitz N, Engert A, Einsele H, Müller-Hermelink HK, Wilhelm M. Autologous stem-cell transplantation as first-line therapy in peripheral T-cell lymphomas: results of a prospective multicenter study. J Clin Oncol. 2009 Jan 1;27(1):106-13. Epub 2008 Nov 24. link to original article PubMed
Relapsed/refractory, randomized data
DHAP
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DHAP: Dexamethasone, High-dose Ara-C (Cytarabine), Platinol (Cisplatin)
Regimen
Study | Evidence | Comparator |
Crump et al. 2014 (NCIC-CTG LY.12) | Phase III, <20 in this arm | GDP |
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
- Cytarabine (Cytosar) 2000 mg/m2 IV over 3 hours Q12H x 2 doses on day 2 (total of 2 doses)
- Cisplatin (Platinol) 100 mg/m2 IV continuous infusion over 24 hours on day 1
21-day cycles x up to 3 cycles
References
- Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized Comparison of Gemcitabine, Dexamethasone, and Cisplatin Versus Dexamethasone, Cytarabine, and Cisplatin Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed and Refractory Aggressive Lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. link to original article contains verified protocol PubMed
GDP
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GDP: Gemcitabine, Dexamethasone, Platinol (Cisplatin)
Regimen
Study | Evidence | Comparator |
Crump et al. 2014 (NCIC-CTG LY.12) | Phase III, <20 in this arm | DHAP |
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
21-day cycles x up to 3 cycles
References
- Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized Comparison of Gemcitabine, Dexamethasone, and Cisplatin Versus Dexamethasone, Cytarabine, and Cisplatin Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed and Refractory Aggressive Lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. link to original article contains verified protocol PubMed
Relapsed/refractory, non-randomized or retrospective data
Belinostat (Beleodaq)
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Regimen
Study | Evidence | ||
Foss et al. 2014 | Phase II | ||
O'Connor et al. 2015 (BELIEF) | Phase II |
- Belinostat (Beleodaq) 1000 mg/m2 IV over 30 minutes once per day on days 1 to 5
3-week cycles
References
- Foss F, Advani R, Duvic M, Hymes KB, Intragumtornchai T, Lekhakula A, Shpilberg O, Lerner A, Belt RJ, Jacobsen ED, Laurent G, Ben-Yehuda D, Beylot-Barry M, Hillen U, Knoblauch P, Bhat G, Chawla S, Allen LF, Pohlman B. A Phase II trial of Belinostat (PXD101) in patients with relapsed or refractory peripheral or cutaneous T-cell lymphoma. Br J Haematol. 2014 Nov 17. [Epub ahead of print] link to original article contains protocol PubMed
- O'Connor OA, Horwitz S, Masszi T, Van Hoof A, Brown P, Doorduijn J, Hess G, Jurczak W, Knoblauch P, Chawla S, Bhat G, Choi MR, Walewski J, Savage K, Foss F, Allen LF, Shustov A. Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study. J Clin Oncol. 2015 Aug 10;33(23):2492-9. Epub 2015 Jun 22. link to original article contains verified protocol PubMed
Bendamustine (Bendeka)
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Regimen
Study | Evidence |
Demaj et al. 2013 (BENTLY) | Phase II |
- Bendamustine (Bendeka) 120 mg/m2 IV over 30 to 60 minutes once per day on days 1 & 2
3-week cycle x 6 cycles
References
- Damaj G, Gressin R, Bouabdallah K, Cartron G, Choufi B, Gyan E, Banos A, Jaccard A, Park S, Tournilhac O, Schiano-de Collela JM, Voillat L, Joly B, Le Gouill S, Saad A, Cony-Makhoul P, Vilque JP, Sanhes L, Schmidt-Tanguy A, Bubenheim M, Houot R, Diouf M, Marolleau JP, Béné MC, Martin A, Lamy T. Results from a prospective, open-label, phase II trial of bendamustine in refractory or relapsed T-cell lymphomas: the BENTLY trial. J Clin Oncol. 2013 Jan 1;31(1):104-10. Epub 2012 Oct 29. link to original article contains verified protocol PubMed
Brentuximab vedotin (Adcetris)
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Regimen
Study | Evidence |
Horwitz et al. 2014 | Phase II |
- Brentuximab vedotin (Adcetris) 1.8 mg/kg IV on day 1
3-week cycle until progression or unacceptable toxicity
References
- Horwitz SM, Advani RH, Bartlett NL, Jacobsen ED, Sharman JP, O'Connor OA, Siddiqi T, Kennedy DA, Oki Y. Objective responses in relapsed T-cell lymphomas with single-agent brentuximab vedotin. Blood. 2014 May 15;123(20):3095-100. Epub 2014 Mar 20. link to original article contains verified protocol PubMed
Lenalidomide (Revlimid)
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Regimen
Study | Evidence | ||
Dueck et al. 2010 | Phase II | ||
Morschhauser et al. 2013 (EXPECT) | Phase II |
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
28-day cycles
Dueck et al. 2010 specifies indefinite duration, stopping for progression or intolerance. EXPECT specifies a treatment duration of up to 2 years.
References
- Morschhauser F, Fitoussi O, Haioun C, Thieblemont C, Quach H, Delarue R, Glaisner S, Gabarre J, Bosly A, Lister J, Li J, Coiffier B. A phase 2, multicentre, single-arm, open-label study to evaluate the safety and efficacy of single-agent lenalidomide (Revlimid®) in subjects with relapsed or refractory peripheral T-cell non-Hodgkin lymphoma: The EXPECT trial. Eur J Cancer. 2013 Sep;49(13):2869-76. Epub 2013 May 31. link to original article contains protocol PubMed
- Dueck G, Chua N, Prasad A, Finch D, Stewart D, White D, van der Jagt R, Johnston J, Belch A, Reiman T. Interim report of a phase 2 clinical trial of lenalidomide for T-cell non-Hodgkin lymphoma. Cancer. 2010 Oct 1;116(19):4541-8. link to original article contains verified protocol PubMed
- Update: Toumishey E, Prasad A, Dueck G, Chua N, Finch D, Johnston J, van der Jagt R, Stewart D, White D, Belch A, Reiman T. Final report of a phase 2 clinical trial of lenalidomide monotherapy for patients with T-cell lymphoma. Cancer. 2014 Oct 29. [Epub ahead of print] link to original article PubMed
Pralatrexate (Folotyn)
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Regimen
Study | Evidence |
O'Connor et al. 2011 (PROPEL) | Phase II |
- Pralatrexate (Folotyn) 30 mg/m2 IV push over 3 to 5 minutes once per day on days 1, 8, 15, 22, 29, 36
Supportive medications:
- Cyanocobalamin (Vitamin B12) 1 mg IM once every 8 to 10 weeks
- Folic acid (Folate) 1 to 1.25 mg PO once per day
- "Elevated methylmalonic acid (>200 nmol/L) and/or homocysteine (>10 µmol/L) at screening required initiation of Folic acid (Folate) and Cyanocobalamin (Vitamin B12) = 10 days before the first dose of Pralatrexate (Folotyn)."
7-week cycles, given until progression of disease, unacceptable toxicity, or patient/physician preference
Example orders
References
- O'Connor OA, Pro B, Pinter-Brown L, Bartlett N, Popplewell L, Coiffier B, Lechowicz MJ, Savage KJ, Shustov AR, Gisselbrecht C, Jacobsen E, Zinzani PL, Furman R, Goy A, Haioun C, Crump M, Zain JM, Hsi E, Boyd A, Horwitz S. Pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma: results from the pivotal PROPEL study. J Clin Oncol. 2011 Mar 20;29(9):1182-9. link to original article contains verified protocol PubMed
Romidepsin (Istodax)
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Regimen
Study | Evidence | ||
Piekarz et al. 2011 | Phase II | ||
Coiffier et al. 2012 | Phase II |
- Romidepsin (Istodax) 14 mg/m2 IV over 4 hours once per day on days 1, 8, 15
28-day cycles, up to 6 cycles, with optional extension of treatment for patients with stable disease or response
References
- Piekarz RL, Frye R, Prince HM, Kirschbaum MH, Zain J, Allen SL, Jaffe ES, Ling A, Turner M, Peer CJ, Figg WD, Steinberg SM, Smith S, Joske D, Lewis I, Hutchins L, Craig M, Fojo AT, Wright JJ, Bates SE. Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma. Blood. 2011 Jun 2;117(22):5827-34. Epub 2011 Feb 25. link to original article contains verified protocol PubMed
- Coiffier B, Pro B, Prince HM, Foss F, Sokol L, Greenwood M, Caballero D, Borchmann P, Morschhauser F, Wilhelm M, Pinter-Brown L, Padmanabhan S, Shustov A, Nichols J, Carroll S, Balser J, Balser B, Horwitz S. Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy. J Clin Oncol. 2012 Feb 20;30(6):631-6. Epub 2012 Jan 23. link to original article contains verified protocol PubMed
- Update: Coiffier B, Pro B, Prince HM, Foss F, Sokol L, Greenwood M, Caballero D, Morschhauser F, Wilhelm M, Pinter-Brown L, Padmanabhan Iyer S, Shustov A, Nielsen T, Nichols J, Wolfson J, Balser B, Horwitz S. Romidepsin for the treatment of relapsed/refractory peripheral T-cell lymphoma: pivotal study update demonstrates durable responses. J Hematol Oncol. 2014 Jan 23;7(1):11. link to original article PubMed