CNS lymphoma
Use of this site is subject to you reading and agreeing with the terms set forth in the disclaimer.
Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are invited to contribute to the site.
42 regimens on this page
60 variants on this page
|
Untreated, randomized data
Cytarabine & Methotrexate
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
Ferreri et al. 2009 | Randomized Phase II, >20 per arm | High-dose MTX | Seems to have superior CRR |
- Methotrexate (MTX) 3500 mg/m2 IV once on day 1: first 500 mg/m2 given over 15 minutes, remaining 3000 mg/m2 given over 3 hours
- Cytarabine (Cytosar) 2000 mg/m2 IV bid on days 2 & 3
21-day cycles x 4 cycles
Followed within 4 weeks by whole brain irradiation.
References
- Ferreri AJ, Reni M, Foppoli M, Martelli M, Pangalis GA, Frezzato M, Cabras MG, Fabbri A, Corazzelli G, Ilariucci F, Rossi G, Soffietti R, Stelitano C, Vallisa D, Zaja F, Zoppegno L, Aondio GM, Avvisati G, Balzarotti M, Brandes AA, Fajardo J, Gomez H, Guarini A, Pinotti G, Rigacci L, Uhlmann C, Picozzi P, Vezzulli P, Ponzoni M, Zucca E, Caligaris-Cappio F, Cavalli F; International Extranodal Lymphoma Study Group (IELSG). High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial. Lancet. 2009 Oct 31;374(9700):1512-20. Epub 2009 Sep 18. link to original article contains verified protocol PubMed
Methotrexate (MTX)
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
Ferreri et al. 2009 | Randomized Phase II, >20 per arm | High-dose MTX & Cytarabine | Seems to have inferior CRR |
- Methotrexate (MTX) 3500 mg/m2 IV once on day 1: first 500 mg/m2 given over 15 minutes, remaining 3000 mg/m2 given over 3 hours
21-day cycles x 4 cycles
Followed within 4 weeks by whole brain irradiation.
References
- Ferreri AJ, Reni M, Foppoli M, Martelli M, Pangalis GA, Frezzato M, Cabras MG, Fabbri A, Corazzelli G, Ilariucci F, Rossi G, Soffietti R, Stelitano C, Vallisa D, Zaja F, Zoppegno L, Aondio GM, Avvisati G, Balzarotti M, Brandes AA, Fajardo J, Gomez H, Guarini A, Pinotti G, Rigacci L, Uhlmann C, Picozzi P, Vezzulli P, Ponzoni M, Zucca E, Caligaris-Cappio F, Cavalli F; International Extranodal Lymphoma Study Group (IELSG). High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial. Lancet. 2009 Oct 31;374(9700):1512-20. Epub 2009 Sep 18. link to original article contains verified protocol PubMed
Untreated, non-randomized or retrospective data
Ferreri regimen
back to top |
Regimen
Study | Evidence |
Ferreri et al. 2015 | Phase II |
To be completed
References
- Ferreri AJ, Donadoni G, Cabras MG, Patti C, Mian M, Zambello R, Tarella C, Di Nicola M, D'Arco AM, Doa G, Bruno-Ventre M, Assanelli A, Foppoli M, Citterio G, Fanni A, Mulè A, Caligaris-Cappio F, Ciceri F. High Doses of Antimetabolites Followed by High-Dose Sequential Chemoimmunotherapy and Autologous Stem-Cell Transplantation in Patients With Systemic B-Cell Lymphoma and Secondary CNS Involvement: Final Results of a Multicenter Phase II Trial. J Clin Oncol. 2015 Nov 20;33(33):3903-10. Epub 2015 Aug 17. link to original article PubMed
Lomustine, Methotrexate, Methylprednisolone, Procarbazine
back to top |
Regimen
Study | Evidence |
Hoang-Xuan et al. 2003 (EORTC 26952) | Phase II |
This was the first prospective phase II trial evaluating chemotherapy alone in older patients with PCNSL.
- Methotrexate (MTX) 1000 mg/m2 IV once per day on days 1, 10, 20
- Lomustine (Ceenu) 40 mg/m2 PO once on day 1
- Procarbazine (Matulane) 60 mg/m2 PO once per day on days 1 to 7
- Methylprednisolone (Solumedrol) as follows:
- Days 1 to 20: 120 mg/m2 PO/IV every other day
- Days 20 to 45: 60 mg/m2 PO/IV every other day
Intrathecal component:
- Methotrexate (MTX) 15 mg IT (admixed with Cytarabine (Cytosar)) once per day on days 1, 5, 10, 15
- Cytarabine (Cytosar) 40 mg IT (admixed with Methotrexate (MTX)) once per day on days 1, 5, 10, 15
Supportive medications
- Folinic acid (Leucovorin) 25 mg PO every 6 hours for 3 days, initiated 24 hours after IV Methotrexate (MTX) administrations, and 10 mg PO every 6 hours for 2 days after IT Methotrexate (MTX) administrations
45-day course
Patients achieving PR or CR proceeded to lomustine, methotrexate, procarbazine maintenance.'
References
- Hoang-Xuan K, Taillandier L, Chinot O, Soubeyran P, Bogdhan U, Hildebrand J, Frenay M, De Beule N, Delattre JY, Baron B; European Organization for Research and Treatment of Cancer Brain Tumor Group. Chemotherapy alone as initial treatment for primary CNS lymphoma in patients older than 60 years: a multicenter phase II study (26952) of the European Organization for Research and Treatment of Cancer Brain Tumor Group. J Clin Oncol. 2003 Jul 15;21(14):2726-31. link to original article contains verified protocol PubMed
Methotrexate (MTX)
back to top |
Regimen #1
Study | Evidence |
Thiel et al. 2010 (G-PCNSL-SG-1) | Nonrandomized |
All patients received the same induction regimen; however, the induction regimen was changed after 2006 to high-dose MTX & ifosfamide.
- Methotrexate (MTX) 4000 mg/m2 IV once over 4 hours on day 1
14-day cycle x 6 cycles
Patients with a complete response were randomized to whole-brain irradiation versus no further treatment. Patients with less than a complete response in the WB-XRT arm received salvage whole-brain irradiation and those in the no-WB-XRT arm received salvage HiDAC.
Regimen #2
Study | Evidence |
Montemurro et al. 2007 (OSHO-53) | Phase II |
- Methotrexate (MTX) as follows:
- Patients < 60 years old: 8000 mg/m2 IV over 4 hours once per day on days 1 & 10
- Patients > 60 years old: 6000 mg/m2 IV over 4 hours once per day on days 1 & 10
One course
Responders (CR or PR) proceeded to Bu/TT -> Autologous stem cell transplant.
Regimen #3
Study | Evidence |
Herrlinger et al. 2005 (NOA-03) | Phase II |
This was considered a negative trial by the authors and is included here for historical purposes.
- Methotrexate (MTX) 8000 mg/m2 IV once over 4 hours on day 1
14-day cycle x 6 cycles
Patients intolerant of MTX or not achieving CR after 6 cycles were randomized to salvage whole-brain irradiation versus PCV; see article for details.
Regimen #4
Study | Evidence |
Batchelor et al. 2003 | Phase II |
- Methotrexate (MTX) 8000 mg/m2 IV once over 4 hours on day 1
- The full dose of 8000 mg/m2 was only given if CrCl was at least 100. For CrCl less than 100, the dose was reduced by the percentage reduction below 100. For example, a CrCl of 50 would mandate a 50% dose reduction.
14-day cycle until CR or a maximum of 8 cycles
Patients achieving CR received two more cycles at the same dose and frequency and then proceeded to methotrexate maintenance.
References
- Batchelor T, Carson K, O'Neill A, Grossman SA, Alavi J, New P, Hochberg F, Priet R. Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: a report of NABTT 96-07. J Clin Oncol. 2003 Mar 15;21(6):1044-9. link to original article contains verified protocol PubMed
- Herrlinger U, Küker W, Uhl M, Blaicher HP, Karnath HO, Kanz L, Bamberg M, Weller M; Neuro-Oncology Working Group of the German Society. NOA-03 trial of high-dose methotrexate in primary central nervous system lymphoma: final report. Ann Neurol. 2005 Jun;57(6):843-7. link to original article contains verified protocol PubMed content property of HemOnc.org
- Montemurro M, Kiefer T, Schüler F, Al-Ali HK, Wolf HH, Herbst R, Haas A, Helke K, Theilig A, Lotze C, Hirt C, Niederwieser D, Schwenke M, Krüger WH, Dölken G. Primary central nervous system lymphoma treated with high-dose methotrexate, high-dose busulfan/thiotepa, autologous stem-cell transplantation and response-adapted whole-brain radiotherapy: results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study. Ann Oncol. 2007 Apr;18(4):665-71. Epub 2006 Dec 21. link to original article contains verified protocol PubMed
- Thiel E, Korfel A, Martus P, Kanz L, Griesinger F, Rauch M, Röth A, Hertenstein B, von Toll T, Hundsberger T, Mergenthaler HG, Leithäuser M, Birnbaum T, Fischer L, Jahnke K, Herrlinger U, Plasswilm L, Nägele T, Pietsch T, Bamberg M, Weller M. High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial. Lancet Oncol. 2010 Nov;11(11):1036-47. Epub 2010 Oct 20. link to original article contains verified protocol PubMed
- Update: Abstract: Agnieszka Korfel, Eckhard Thiel, Peter Martus, Robert Moehle, Frank Griesinger, Michael Rauch, Alexander Roeth, Bernd Hertenstein, Thomas Fischer, Thomas Hundsberger, Hans-Guenther Mergenthaler, Christian Junghanss, Tobias Birnbaum, Lars Fischer, Kristoph Jahnke, Ulrich Herrlinger, Ludwig Plasswilm, Thomas Naegele, Torsten Pietsch, Michael Weller. G-PCNSL-SG-1 randomized phase III trial of high-dose methotrexate with or without whole brain radiotherapy for primary central nervous system lymphoma: Long-term follow-up. J Clin Oncol 32:5s, 2014 (suppl; abstr 8527) link to abstract
- Update: Korfel A, Thiel E, Martus P, Möhle R, Griesinger F, Rauch M, Röth A, Hertenstein B, Fischer T, Hundsberger T, Mergenthaler HG, Junghanß C, Birnbaum T, Fischer L, Jahnke K, Herrlinger U, Roth P, Bamberg M, Pietsch T, Weller M. Randomized phase III study of whole-brain radiotherapy for primary CNS lymphoma. Neurology. 2015 Mar 24;84(12):1242-8. Epub 2015 Feb 25. link to original article PubMed
Methotrexate -> Cytarabine
back to top |
Regimen
Study | Evidence |
Abrey et al. 2003 | Phase II |
Part One
- Methotrexate (MTX) 3500 mg/m2 (capped at 7000 mg) IV over 2 hours once on day 1
Supportive medications
- Folinic acid (Leucovorin) 25 mg PO every 6 hours, beginning 24 hours after start of Methotrexate (MTX), continued for 12 doses or until serum MTX level < 0.10
2-week cycle x 5 cycles
Patients proceed to part two 72 hours after 5th dose of MTX or once the 5th dose MTX level has cleared:
Part Two
- Cytarabine (Cytosar) 3000 mg/m2 IV once per day on days 1 & 2
Supportive medications
- Filgrastim (Neupogen) as follows:
- Cycle 1: 10 mcg/kg SC once per day starting on day 4 and continued until stem cell collection complete
- Cycle 2: 5 mcg/kg SC once per day continued for 2 weeks or until ANC > 3000/μL
1-month cycle x 2 cycles
Stem cell collection took place after the first cycle. Treatment was followed by BEAM -> autologous stem cell transplant.
References
- Abrey LE, Moskowitz CH, Mason WP, Crump M, Stewart D, Forsyth P, Paleologos N, Correa DD, Anderson ND, Caron D, Zelenetz A, Nimer SD, DeAngelis LM. Intensive methotrexate and cytarabine followed by high-dose chemotherapy with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma: an intent-to-treat analysis. J Clin Oncol. 2003 Nov 15;21(22):4151-6. link to original article contains verified protocol PubMed
Methotrexate -> Cytarabine & Thiotepa
back to top |
Regimen #1
Study | Evidence |
Illerhaus et al. 2006 | Phase II |
- Methotrexate (MTX) 8000 mg/m2 IV over 4 hours once per day on days 1, 10, 20
Supportive medications
- Folinic acid (Leucovorin) 15 mg/m2 every 6 hours, beginning 24 hours after start of Methotrexate (MTX), continuing until clearance
One course
Patients with CR, PR, or SD "with clinical improvement" after the 2nd dose of MTX proceeded to:
- Cytarabine (Cytosar) 3 g/m2 IV over 3 hours once per day on days 30 & 31
- Thiotepa (Thioplex) 40 mg/m2 (route not specified) once on day 31
One course
This was for stem cell mobilization and was followed by BCNU/TT -> autologous stem cell transplant.
Regimen #2
Study | Evidence |
Illerhaus et al. 2008 | Pilot, <20 patients |
- Methotrexate (MTX) 8000 mg/m2 IV over 4 hours once on day 1
Supportive medications
- Folinic acid (Leucovorin) 15 mg/m2 every 6 hours, beginning 24 hours after start of Methotrexate (MTX), continuing until clearance
10-day cycle x 2 to 4 cycles, followed by:
- Cytarabine (Cytosar) 3 g/m2 IV once per day on days 1 & 2
- Thiotepa (Thioplex) 40 mg/m2 (route not specified) once on day 2
21-day cycle x 2 cycles
Stem cells are mobilized and collected after the first cycle; this part was followed by BCNU/TT -> autologous stem cell transplant.
References
- Illerhaus G, Marks R, Ihorst G, Guttenberger R, Ostertag C, Derigs G, Frickhofen N, Feuerhake F, Volk B, Finke J. High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3865-70. Epub 2006 Jul 24. link to original article contains verified protocol PubMed
- Illerhaus G, Müller F, Feuerhake F, Schäfer AO, Ostertag C, Finke J. High-dose chemotherapy and autologous stem-cell transplantation without consolidating radiotherapy as first-line treatment for primary lymphoma of the central nervous system. Haematologica. 2008 Jan;93(1):147-8. link to original article contains verified protocol PubMed
Methotrexate & Ifosfamide
back to top |
Regimen
Study | Evidence |
Thiel et al. 2010 (G-PCNSL-SG-1) | Nonrandomized |
All patients received the same induction regimen; however, the induction regimen was high-dose MTX until 2006.
- Methotrexate (MTX) 4000 mg/m2 IV over 4 hours once on day 1
- Ifosfamide (Ifex) 1500 g/m2 IV over 3 hours once per day on days 3 to 5
14-day cycle x 6 cycles
Patients with a complete response were randomized to whole-brain irradiation versus no further treatment. Patients with less than a complete response in the WB-XRT arm received salvage whole-brain irradiation and those in the no-WB-XRT arm received salvage HiDAC.
References
- Thiel E, Korfel A, Martus P, Kanz L, Griesinger F, Rauch M, Röth A, Hertenstein B, von Toll T, Hundsberger T, Mergenthaler HG, Leithäuser M, Birnbaum T, Fischer L, Jahnke K, Herrlinger U, Plasswilm L, Nägele T, Pietsch T, Bamberg M, Weller M. High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial. Lancet Oncol. 2010 Nov;11(11):1036-47. Epub 2010 Oct 20. link to original article contains verified protocol PubMed
- Update: Abstract: Agnieszka Korfel, Eckhard Thiel, Peter Martus, Robert Moehle, Frank Griesinger, Michael Rauch, Alexander Roeth, Bernd Hertenstein, Thomas Fischer, Thomas Hundsberger, Hans-Guenther Mergenthaler, Christian Junghanss, Tobias Birnbaum, Lars Fischer, Kristoph Jahnke, Ulrich Herrlinger, Ludwig Plasswilm, Thomas Naegele, Torsten Pietsch, Michael Weller. G-PCNSL-SG-1 randomized phase III trial of high-dose methotrexate with or without whole brain radiotherapy for primary central nervous system lymphoma: Long-term follow-up. J Clin Oncol 32:5s, 2014 (suppl; abstr 8527) link to abstract
- Update: Korfel A, Thiel E, Martus P, Möhle R, Griesinger F, Rauch M, Röth A, Hertenstein B, Fischer T, Hundsberger T, Mergenthaler HG, Junghanß C, Birnbaum T, Fischer L, Jahnke K, Herrlinger U, Roth P, Bamberg M, Pietsch T, Weller M. Randomized phase III study of whole-brain radiotherapy for primary CNS lymphoma. Neurology. 2015 Mar 24;84(12):1242-8. Epub 2015 Feb 25. link to original article PubMed
MPV
back to top |
MPV: Methotrexate, Procarbazine, Vincristine
Regimen
Study | Evidence |
DeAngelis et al. 2002 (RTOG 93-10) | Phase II |
- Methotrexate (MTX) 2500 mg/m2 IV once over 2 to 3 hours on day 1
- Procarbazine (Matulane) 100 mg/m2 PO once per day on days 1 to 7 of odd cycles (1, 3, 5)
- Vincristine (Oncovin) 1.4 mg/m2 (capped at 2.8 mg) IV on day 1
Intrathecal component:
- Methotrexate (MTX) 12 mg IT (via Ommaya) once one week after IV Methotrexate (MTX) administration
- Folinic acid (Leucovorin) 10 mg PO every 6 hours x 8 doses, beginning the evening of IT Methotrexate (MTX) administration
Supportive medications
- Folinic acid (Leucovorin) 20 mg PO every 6 hours x 12 doses, beginning 24 hours after IV Methotrexate (MTX) administration
- Dexamethasone (Decadron) 16 mg PO once per day x 7 days, then 12 mg PO once per day x 7 days, then 8 mg PO once per day x 7 days, then 6 mg PO once per day x 7 days, then 4 mg PO once per day x 7 days, then 2 mg PO once per day x 7 days (starts with first cycle)
14-day cycles x 5 cycles, followed by:
- Whole-brain irradiation to 45 Gy in 1.80-Gy fractions or to 36 Gy in 1.20-Gy twice-daily fractions
References
- DeAngelis LM, Seiferheld W, Schold SC, Fisher B, Schultz CJ; Radiation Therapy Oncology Group Study 93-10. Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10. J Clin Oncol. 2002 Dec 15;20(24):4643-8. link to original article contains verified protocol PubMed
MT-R
back to top |
MT-R: Methotrexate, Temozolomide, Rituximab
Regimen
Study | Evidence |
Rubenstein et al. 2013 (CALGB 50202) | Phase II |
Induction phase
- Methotrexate (MTX) 8000 mg/m2 IV once over 4 hours on day 1
- Given for a total of 7 doses.
- Temozolomide (Temodar) 150 mg/m2 PO once per day on days 7 to 11 (odd cycles only)
- Rituximab (Rituxan) 375 mg/m2 IV once on day 3
- Rituximab omitted for T-cell PCNSL and given for a total of 6 doses in all others.
Supportive medications
- Folinic acid (Leucovorin) 100 mg/m2 IV every 6 hours, start on day 2, continue until MTX level <0.05
14-day cycles x 8 cycles
Patients achieving CR or CRu were given one additional cycle of methotrexate & temozolomide, followed by consolidation therapy:
Consolidation
- Etoposide (Vepesid) 40 mg/kg IV continuous infusion over 96 hours, days 1 to 4
- Cytarabine (Cytosar) 2 gm/m2 IV Q12H over 2 hours × 8 doses, days 1 to 4
One course
References
- Rubenstein JL, Hsi ED, Johnson JL, Jung SH, Nakashima MO, Grant B, Cheson BD, Kaplan LD. Intensive Chemotherapy and Immunotherapy in Patients With Newly Diagnosed Primary CNS Lymphoma: CALGB 50202 (Alliance 50202). J Clin Oncol. 2013 Sep 1;31(25):3061-8. Epub 2013 Apr 8 link to original article contains verified protocol PubMed
MVBP
back to top |
MVBP: Methotrexate, VP16 (Etoposide), BCNU (Carmustine), MethylPrednisolone
Regimen
Study | Evidence |
Colombat et al. 2006 | Phase II |
- Methotrexate (MTX) 3000 mg/m2 IV once per day on days 1 & 15
- Etoposide (Vepesid) 100 mg/m2 IV once on day 2
- Carmustine (BiCNU) 100 mg/m2 IV once on day 3
- Methylprednisolone (Solumedrol) 60 mg/m2 (route not specified) once per day on days 1 to 5
Intrathecal component: 6 doses total, timing is not specified
- Methotrexate (MTX) 20 mg IT (admixed with Cytarabine (Cytosar) and Methylprednisolone (Solumedrol))
- Cytarabine (Cytosar) 50 mg IT (admixed with Methotrexate (MTX) and Methylprednisolone (Solumedrol))
- Methylprednisolone (Solumedrol) 40 mg IT (admixed with Cytarabine (Cytosar) and Methotrexate (MTX))
Supportive medications
- Folinic acid (Leucovorin) details not specified
2 courses, separated by 21 days
Responding patients (CR or PR) proceeded to cytarabine & ifosfamide for stem cell mobilization, followed by BEAM -> autologous stem cell transplant. Non-responders received cytarabine & etoposide salvage
References
- Colombat P, Lemevel A, Bertrand P, Delwail V, Rachieru P, Brion A, Berthou C, Bay JO, Delepine R, Desablens B, Camilleri-Broët S, Linassier C, Lamy T. High-dose chemotherapy with autologous stem cell transplantation as first-line therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter phase II study of the GOELAMS group. Bone Marrow Transplant. 2006 Sep;38(6):417-20. link to original article contains verified protocol PubMed
Nordic Regimen, older patients
back to top |
Regimen
Study | Evidence |
Pulczynski et al. 2015 | Phase II |
This regimen is meant for patients aged 66-75 years.
A cycles
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1 of the 1st A cycle only
- Methotrexate (MTX) 3000 mg/m2 IV once on day 1
- Ifosfamide (Ifex) 800 mg/m2 IV once per day on days 2 to 5 of the 1st A cycle only
- Dexamethasone (Decadron) 10 mg/m2/day PO on days 2 to 5
- Cytarabine liposomal (DepoCyt) 50 mg IT once on day 2
B cycles
- Methotrexate (MTX) 5000 mg/m2 IV once on day 1
- Dexamethasone (Decadron) 10 mg/m2/day PO on days 2 to 5
- Cytarabine liposomal (DepoCyt) 50 mg IT once on day 2
- Cyclophosphamide (Cytoxan) 150 mg/m2 IV once per day on days 2 to 6
C cycles
- Dexamethasone (Decadron) 20 mg/m2/day PO on days 3 to 7
- Cytarabine (Cytosar) 1000 mg/m2 IV q12h on days 1 & 2
- Vindesine (Eldisine) 5 mg IV once on day 1
21-day cycle x 6 cycles (A -> B -> C -> A -> B -> C)
Treatment followed by temozolomide maintenance.
References
- Pulczynski EJ, Kuittinen O, Erlanson M, Hagberg H, Fosså A, Eriksson M, Nordstrøm M, Østenstad B, Fluge Ø, Leppä S, Fiirgaard B, Bersvendsen H, Fagerli UM. Successful change of treatment strategy in elderly patients with primary central nervous system lymphoma by de-escalating induction and introducing temozolomide maintenance: results from a phase II study by the Nordic Lymphoma Group. Haematologica. 2015 Apr;100(4):534-40. Epub 2014 Dec 5. link to original article contains verified protocol in supplement PubMed
Nordic Regimen, younger patients
back to top |
Regimen
Study | Evidence |
Pulczynski et al. 2015 | Phase II |
This regimen is meant for patients aged 18-65 years.
A cycles
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1 of the 1st A cycle only
- Methotrexate (MTX) 5000 mg/m2 IV once on day 1
- Ifosfamide (Ifex) 800 mg/m2 IV once per day on days 2 to 5
- Dexamethasone (Decadron) 10 mg/m2/day PO on days 2 to 5
- Cytarabine liposomal (DepoCyt) 50 mg IT once on day 2
B cycles
- Methotrexate (MTX) 5000 mg/m2 IV once on day 1
- Dexamethasone (Decadron) 10 mg/m2/day PO on days 2 to 5
- Vincristine (Oncovin) 2 mg IV once on day 1
- Cytarabine liposomal (DepoCyt) 50 mg IT once on day 2
- Cyclophosphamide (Cytoxan) 200 mg/m2 IV once per day on days 2 to 5
C cycles
- Dexamethasone (Decadron) 20 mg/m2/day PO on days 3 to 7
- Cytarabine (Cytosar) 1500 mg/m2 IV q12h on days 1 & 2
- Vindesine (Eldisine) 5 mg IV once on day 1
21-day cycle x 6 cycles (A -> B -> C -> A -> B -> C)
References
- Pulczynski EJ, Kuittinen O, Erlanson M, Hagberg H, Fosså A, Eriksson M, Nordstrøm M, Østenstad B, Fluge Ø, Leppä S, Fiirgaard B, Bersvendsen H, Fagerli UM. Successful change of treatment strategy in elderly patients with primary central nervous system lymphoma by de-escalating induction and introducing temozolomide maintenance: results from a phase II study by the Nordic Lymphoma Group. Haematologica. 2015 Apr;100(4):534-40. Epub 2014 Dec 5. link to original article contains verified protocol in supplement PubMed
R-MPV
back to top |
R-MPV: Rituximab, Methotrexate, Procarbazine, Vincristine
Regimen
Study | Evidence |
Shah et al. 2007 | Phase II |
Omuro et al. 2015 | Phase II |
- Rituximab (Rituxan) 500 mg/m2 IV once over 5 hours on day 1
- Methotrexate (MTX) 3500 mg/m2 IV once over 2 hours on day 2
- Procarbazine (Matulane) 100 mg/m2 PO once per day on days 1 to 7 of odd cycles
- Vincristine (Oncovin) 1.4 mg/m2 (capped at 2.8 mg) IV once on day 2
Intrathecal component (only described in the Shah et al. 2007 trial):
- Methotrexate (MTX) 12 mg IT (via Ommaya) once sometime between day 5 and 12 (for patients with positive CSF cytology)
Supportive medications
- Folinic acid (Leucovorin) 20 to 25 mg every 6 hours for at least 72 hours or until serum MTX level < 1e-8 mg/dL, beginning 24 hours after IV Methotrexate (MTX) administration
14-day cycle x 5 to 7 cycles
In Shah et al. 2007, followed in 3 to 5 weeks by whole-brain irradiation. In Omuro et al. 2015, patients proceeded to Bu/TT/Cy -> autologous stem cell transplant, after 5 cycles if CR achieved, or after 7 cycles for PR/CR at that time.
References
- Shah GD, Yahalom J, Correa DD, Lai RK, Raizer JJ, Schiff D, LaRocca R, Grant B, DeAngelis LM, Abrey LE. Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma. J Clin Oncol. 2007 Oct 20;25(30):4730-5. Erratum in: J Clin Oncol. 2008 Jan 10;26(2):340. link to original article contains verified protocol PubMed
- Update: Morris PG, Correa DD, Yahalom J, Raizer JJ, Schiff D, Grant B, Grimm S, Lai RK, Reiner AS, Panageas K, Karimi S, Curry R, Shah G, Abrey LE, DeAngelis LM, Omuro A. Rituximab, methotrexate, procarbazine, and vincristine followed by consolidation reduced-dose whole-brain radiotherapy and cytarabine in newly diagnosed primary CNS lymphoma: final results and long-term outcome. J Clin Oncol. 2013 Nov 1;31(31):3971-9. Epub 2013 Oct 7. link to original article PubMed
- Omuro A, Correa DD, DeAngelis LM, Moskowitz CH, Matasar MJ, Kaley TJ, Gavrilovic IT, Nolan C, Pentsova E, Grommes CC, Panageas KS, Baser RE, Faivre G, Abrey LE, Sauter CS. R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma. Blood. 2015 Feb 26;125(9):1403-10. Epub 2015 Jan 7. link to original article contains verified protocol PubMed
Consolidation and/or maintenance after upfront therapy
BCNU/TT -> Autologous stem cell transplant
back to top |
BCNU/TT: BCNU (Carmustine), ThioTepa
Regimen #1
Study | Evidence |
Illerhaus et al. 2006 | Phase II |
Treatment preceded by HD-MTX -> Ara-C & Thiotepa. Note that the day count starts from the very beginning of treatment.
- Carmustine (BiCNU) 400 mg/m2 IV once on day 50
- Thiotepa (Thioplex) 5 mg/kg (route not specified) once per day on days 51 & 52
Supportive medications
- Granulocyte colony-stimulating factor starting on day 61, continued until WBC > 1x10^9/L for 3 days
- "Standard supportive measures were taken according to institutional guidelines."
Stem cells re-infused on day 56
Treatment followed by whole-brain irradiation.
Regimen #2
Study | Evidence |
Illerhaus et al. 2008 | Pilot, <20 patients |
Treatment preceded by HD-MTX -> Ara-C & Thiotepa.
- Carmustine (BiCNU) 400 mg/m2 IV once on day 1
- Thiotepa (Thioplex) 5 mg/kg (route not specified) BID on days 2 & 3
Stem cells re-infused on day 7
References
- Illerhaus G, Marks R, Ihorst G, Guttenberger R, Ostertag C, Derigs G, Frickhofen N, Feuerhake F, Volk B, Finke J. High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3865-70. Epub 2006 Jul 24. link to original article contains verified protocol PubMed
- Illerhaus G, Müller F, Feuerhake F, Schäfer AO, Ostertag C, Finke J. High-dose chemotherapy and autologous stem-cell transplantation without consolidating radiotherapy as first-line treatment for primary lymphoma of the central nervous system. Haematologica. 2008 Jan;93(1):147-8. link to original article contains verified protocol PubMed
BEAM -> Autologous stem cell transplant
back to top |
BEAM: BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan
Regimen #1
Study | Evidence |
Colombat et al. 2006 | Phase II |
Treatment preceded by MVBP x 2.
- Carmustine (BiCNU) 300 mg/m2 IV once on day 1
- Etoposide (Vepesid) 200 mg/m2 IV once per day on days 2 to 5
- Cytarabine (Cytosar) 100 mg/m2 IV Q12H on days 2 to 5
- Melphalan (Alkeran) 140 mg/m2 IV once on day 6
Day of transplant is not specified
Treatment followed by whole-brain irradiation.
Regimen #2
Study | Evidence |
Abrey et al. 2003 | Phase II |
Treatment preceded by methotrexate -> cytarabine.
- Carmustine (BiCNU) 300 mg/m2 IV once on day -7
- Etoposide (Vepesid) 100 mg/m2 IV q12h on days -6 to -3
- Cytarabine (Cytosar) 200 mg/m2 IV q12h on days -6 to -3
- Melphalan (Alkeran) 140 mg/m2 IV once on day -2
Supportive medications
- Filgrastim (Neupogen) 5 mcg/kg SC q12h starting on day +1, continuing until ANC > 1000/μL for 3 days or > 10,000/μL for 1 day
Stem cells reinfused on day 0
References
- Abrey LE, Moskowitz CH, Mason WP, Crump M, Stewart D, Forsyth P, Paleologos N, Correa DD, Anderson ND, Caron D, Zelenetz A, Nimer SD, DeAngelis LM. Intensive methotrexate and cytarabine followed by high-dose chemotherapy with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma: an intent-to-treat analysis. J Clin Oncol. 2003 Nov 15;21(22):4151-6. link to original article contains verified protocol PubMed
- Colombat P, Lemevel A, Bertrand P, Delwail V, Rachieru P, Brion A, Berthou C, Bay JO, Delepine R, Desablens B, Camilleri-Broët S, Linassier C, Lamy T. High-dose chemotherapy with autologous stem cell transplantation as first-line therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter phase II study of the GOELAMS group. Bone Marrow Transplant. 2006 Sep;38(6):417-20. link to original article contains verified protocol PubMed
Bu/TT -> Autologous stem cell transplant
back to top |
Bu/TT: Busulfan, ThioTepa
Regimen
Study | Evidence |
Montemurro et al. 2007 (OSHO-53) | Phase II |
Treatment preceded by HD-MTX x 2.
- Busulfan (Myleran) 4 mg/kg PO four times per day on days −8 to −5
- Thiotepa (Thioplex) 5 mg/kg IV once per day on days -4 & -3
Stem cell re-infusion occurs on day 0
References
- Montemurro M, Kiefer T, Schüler F, Al-Ali HK, Wolf HH, Herbst R, Haas A, Helke K, Theilig A, Lotze C, Hirt C, Niederwieser D, Schwenke M, Krüger WH, Dölken G. Primary central nervous system lymphoma treated with high-dose methotrexate, high-dose busulfan/thiotepa, autologous stem-cell transplantation and response-adapted whole-brain radiotherapy: results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study. Ann Oncol. 2007 Apr;18(4):665-71. Epub 2006 Dec 21. link to original article contains verified protocol PubMed
Bu/TT/Cy -> Autologous stem cell transplant
back to top |
Bu/TT/Cy: Busulfan, ThioTepa, Cyclophosphamide
Regimen
Study | Evidence |
Omuro et al. 2015 | Phase II |
Treatment preceded by R-MPV.
- Busulfan (Myleran) 3.2 mg/kg IV once per day on days −6, −5, and −4
- Thiotepa (Thioplex) 250 mg/m2 IV once per day on days −9, −8, and −7
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days −3 and −2
Stem cell re-infusion occurs on day 0
References
- Omuro A, Correa DD, DeAngelis LM, Moskowitz CH, Matasar MJ, Kaley TJ, Gavrilovic IT, Nolan C, Pentsova E, Grommes CC, Panageas KS, Baser RE, Faivre G, Abrey LE, Sauter CS. R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma. Blood. 2015 Feb 26;125(9):1403-10. Epub 2015 Jan 7. link to original article contains verified protocol PubMed
Lomustine, Methotrexate, Procarbazine
back to top |
Regimen
Study | Evidence |
Hoang-Xuan et al. 2003 (EORTC 26952) | Phase II |
Treatment was preceded by lomustine, methotrexate, methylprednisolone, procarbazine induction.
- Methotrexate (MTX) 1000 mg/m2 IV once on day 1
- Lomustine (Ceenu) 40 mg/m2 PO once on day 1
- Procarbazine (Matulane) 60 mg/m2 PO once per day on days 1 to 7
Intrathecal component:
- Methotrexate (MTX) 15 mg IT (admixed with Cytarabine (Cytosar)) once on day 1
- Cytarabine (Cytosar) 40 mg IT (admixed with Methotrexate (MTX)) once on day 1
Supportive medications
- Folinic acid (Leucovorin) 25 mg PO every 6 hours for 3 days, initiated 24 hours after IV Methotrexate (MTX) administration
6-week cycle x 5 cycles
References
- Hoang-Xuan K, Taillandier L, Chinot O, Soubeyran P, Bogdhan U, Hildebrand J, Frenay M, De Beule N, Delattre JY, Baron B; European Organization for Research and Treatment of Cancer Brain Tumor Group. Chemotherapy alone as initial treatment for primary CNS lymphoma in patients older than 60 years: a multicenter phase II study (26952) of the European Organization for Research and Treatment of Cancer Brain Tumor Group. J Clin Oncol. 2003 Jul 15;21(14):2726-31. link to original article contains verified protocol PubMed
Methotrexate (MTX)
back to top |
Regimen
Study | Evidence |
Batchelor et al. 2003 | Phase II |
Treatment preceded by methotrexate induction.
- Methotrexate (MTX) 8000 mg/m2 IV over 4 hours once on day 1
- The full dose of 8000 mg/m2 was only given if CrCl was at least 100. For CrCl less than 100, the dose was reduced by the percentage reduction below 100. For example, a CrCl of 50 would mandate a 50% dose reduction.
28-day cycle x 11 cycles
References
- Batchelor T, Carson K, O'Neill A, Grossman SA, Alavi J, New P, Hochberg F, Priet R. Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: a report of NABTT 96-07. J Clin Oncol. 2003 Mar 15;21(6):1044-9. link to original article contains verified protocol PubMed
Observation
back to top |
Regimen
Study | Evidence | Comparator |
Thiel et al. 2010 (G-PCNSL-SG-1) | Phase III | Whole-brain irradiation |
Treatment preceded by high-dose MTX x 6 before 2006 or high-dose methotrexate & ifosfamide x 6 after 2006.
No further treatment
References
- Thiel E, Korfel A, Martus P, Kanz L, Griesinger F, Rauch M, Röth A, Hertenstein B, von Toll T, Hundsberger T, Mergenthaler HG, Leithäuser M, Birnbaum T, Fischer L, Jahnke K, Herrlinger U, Plasswilm L, Nägele T, Pietsch T, Bamberg M, Weller M. High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial. Lancet Oncol. 2010 Nov;11(11):1036-47. Epub 2010 Oct 20. link to original article contains verified protocol PubMed
- Update: Abstract: Agnieszka Korfel, Eckhard Thiel, Peter Martus, Robert Moehle, Frank Griesinger, Michael Rauch, Alexander Roeth, Bernd Hertenstein, Thomas Fischer, Thomas Hundsberger, Hans-Guenther Mergenthaler, Christian Junghanss, Tobias Birnbaum, Lars Fischer, Kristoph Jahnke, Ulrich Herrlinger, Ludwig Plasswilm, Thomas Naegele, Torsten Pietsch, Michael Weller. G-PCNSL-SG-1 randomized phase III trial of high-dose methotrexate with or without whole brain radiotherapy for primary central nervous system lymphoma: Long-term follow-up. J Clin Oncol 32:5s, 2014 (suppl; abstr 8527) link to abstract
- Update: Korfel A, Thiel E, Martus P, Möhle R, Griesinger F, Rauch M, Röth A, Hertenstein B, Fischer T, Hundsberger T, Mergenthaler HG, Junghanß C, Birnbaum T, Fischer L, Jahnke K, Herrlinger U, Roth P, Bamberg M, Pietsch T, Weller M. Randomized phase III study of whole-brain radiotherapy for primary CNS lymphoma. Neurology. 2015 Mar 24;84(12):1242-8. Epub 2015 Feb 25. link to original article PubMed
Temozolomide (Temodar)
back to top |
Regimen
Study | Evidence |
Pulczynski et al. 2015 | Phase II |
Treatment preceded by the Nordic Regimen for older patients.
- Temozolomide (Temodar) 150 mg/m2/day PO on days 1 to 5
28-day cycles for one year or until relapse/progression
References
- Pulczynski EJ, Kuittinen O, Erlanson M, Hagberg H, Fosså A, Eriksson M, Nordstrøm M, Østenstad B, Fluge Ø, Leppä S, Fiirgaard B, Bersvendsen H, Fagerli UM. Successful change of treatment strategy in elderly patients with primary central nervous system lymphoma by de-escalating induction and introducing temozolomide maintenance: results from a phase II study by the Nordic Lymphoma Group. Haematologica. 2015 Apr;100(4):534-40. Epub 2014 Dec 5. link to original article contains verified protocol in supplement PubMed
Whole brain irradiation
back to top |
Regimen #1
Study | Evidence | Comparator |
Thiel et al. 2010 (G-PCNSL-SG-1) | Phase III | No further treatment |
Treatment preceded by high-dose MTX x 6 before 2006 or high-dose methotrexate & ifosfamide x 6 after 2006.
- Whole-brain irradiation to 45 Gy in 1.5-Gy fractions
Regimen #2
Study | Evidence |
Ferreri et al. 2009 | Nonrandomized |
Treatment preceded by high-dose MTX x 4 versus high-dose MTX & cytarabine x4.
- Any responders: Whole-brain irradiation to 36 Gy plus 9 Gy boost to the tumor bed
- Stable or progressive disease: Whole-brain irradiation to 40 Gy plus 9 Gy boost to the tumor bed
Regimen #3
Study | Evidence |
Shah et al. 2007 | Phase II |
Treatment preceded by R-MPV x 5 to 7 cycles.
- Complete responders: Whole-brain irradiation to 23.4 Gy in 1.80-Gy fractions
- All others: Whole-brain irradiation to 45 Gy in 1.80-Gy fractions
Regimen #4
Study | Evidence |
Colombat et al. 2006 | Phase II |
Treatment preceded by BEAM -> autologous stem cell transplant.
- Complete responders: Whole-brain irradiation to 30 Gy in 1.8-Gy fractions
- Partial responders: Whole-brain irradiation to 30 Gy in 1.8-Gy fractions plus 10 Gy boost to the tumor bed
Regimen #5
Study | Evidence |
Illerhaus et al. 2006 | Phase II |
Treatment preceded by BCNU/TT -> autologous stem cell transplant. Note that the day count starts from the very beginning of treatment.
- Complete responders: Whole-brain irradiation to 45 Gy in 1-Gy fractions, starting on day 90
- Partial responders: Whole-brain irradiation to 50 Gy in 1-Gy fractions, starting on day 90
References
- Illerhaus G, Marks R, Ihorst G, Guttenberger R, Ostertag C, Derigs G, Frickhofen N, Feuerhake F, Volk B, Finke J. High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3865-70. Epub 2006 Jul 24. link to original article contains verified protocol PubMed
- Colombat P, Lemevel A, Bertrand P, Delwail V, Rachieru P, Brion A, Berthou C, Bay JO, Delepine R, Desablens B, Camilleri-Broët S, Linassier C, Lamy T. High-dose chemotherapy with autologous stem cell transplantation as first-line therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter phase II study of the GOELAMS group. Bone Marrow Transplant. 2006 Sep;38(6):417-20. link to original article contains verified protocol PubMed
- Shah GD, Yahalom J, Correa DD, Lai RK, Raizer JJ, Schiff D, LaRocca R, Grant B, DeAngelis LM, Abrey LE. Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma. J Clin Oncol. 2007 Oct 20;25(30):4730-5. Erratum in: J Clin Oncol. 2008 Jan 10;26(2):340. link to original article contains verified protocol PubMed
- Update: Morris PG, Correa DD, Yahalom J, Raizer JJ, Schiff D, Grant B, Grimm S, Lai RK, Reiner AS, Panageas K, Karimi S, Curry R, Shah G, Abrey LE, DeAngelis LM, Omuro A. Rituximab, methotrexate, procarbazine, and vincristine followed by consolidation reduced-dose whole-brain radiotherapy and cytarabine in newly diagnosed primary CNS lymphoma: final results and long-term outcome. J Clin Oncol. 2013 Nov 1;31(31):3971-9. Epub 2013 Oct 7. link to original article PubMed
- Ferreri AJ, Reni M, Foppoli M, Martelli M, Pangalis GA, Frezzato M, Cabras MG, Fabbri A, Corazzelli G, Ilariucci F, Rossi G, Soffietti R, Stelitano C, Vallisa D, Zaja F, Zoppegno L, Aondio GM, Avvisati G, Balzarotti M, Brandes AA, Fajardo J, Gomez H, Guarini A, Pinotti G, Rigacci L, Uhlmann C, Picozzi P, Vezzulli P, Ponzoni M, Zucca E, Caligaris-Cappio F, Cavalli F; International Extranodal Lymphoma Study Group (IELSG). High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial. Lancet. 2009 Oct 31;374(9700):1512-20. Epub 2009 Sep 18. link to original article contains verified protocol PubMed
- Thiel E, Korfel A, Martus P, Kanz L, Griesinger F, Rauch M, Röth A, Hertenstein B, von Toll T, Hundsberger T, Mergenthaler HG, Leithäuser M, Birnbaum T, Fischer L, Jahnke K, Herrlinger U, Plasswilm L, Nägele T, Pietsch T, Bamberg M, Weller M. High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial. Lancet Oncol. 2010 Nov;11(11):1036-47. Epub 2010 Oct 20. link to original article contains verified protocol PubMed
- Update: Abstract: Agnieszka Korfel, Eckhard Thiel, Peter Martus, Robert Moehle, Frank Griesinger, Michael Rauch, Alexander Roeth, Bernd Hertenstein, Thomas Fischer, Thomas Hundsberger, Hans-Guenther Mergenthaler, Christian Junghanss, Tobias Birnbaum, Lars Fischer, Kristoph Jahnke, Ulrich Herrlinger, Ludwig Plasswilm, Thomas Naegele, Torsten Pietsch, Michael Weller. G-PCNSL-SG-1 randomized phase III trial of high-dose methotrexate with or without whole brain radiotherapy for primary central nervous system lymphoma: Long-term follow-up. J Clin Oncol 32:5s, 2014 (suppl; abstr 8527) link to abstract
- Update: Korfel A, Thiel E, Martus P, Möhle R, Griesinger F, Rauch M, Röth A, Hertenstein B, Fischer T, Hundsberger T, Mergenthaler HG, Junghanß C, Birnbaum T, Fischer L, Jahnke K, Herrlinger U, Roth P, Bamberg M, Pietsch T, Weller M. Randomized phase III study of whole-brain radiotherapy for primary CNS lymphoma. Neurology. 2015 Mar 24;84(12):1242-8. Epub 2015 Feb 25. link to original article PubMed
Relapsed/refractory
Cytarabine (Cytosar)
back to top |
Regimen
Study | Evidence |
Thiel et al. 2010 (G-PCNSL-SG-1) | Non-randomized |
Treatment preceded by non-response to HD-MTX prior to 2006 or methotrexate & ifosfamide after 2006.
- Cytarabine (Cytosar) 3000 mg/m2 IV over 3 hours q12h on days 1 & 2
21-day cycle x 4 cycles
References
- Thiel E, Korfel A, Martus P, Kanz L, Griesinger F, Rauch M, Röth A, Hertenstein B, von Toll T, Hundsberger T, Mergenthaler HG, Leithäuser M, Birnbaum T, Fischer L, Jahnke K, Herrlinger U, Plasswilm L, Nägele T, Pietsch T, Bamberg M, Weller M. High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial. Lancet Oncol. 2010 Nov;11(11):1036-47. Epub 2010 Oct 20. link to original article contains verified protocol PubMed
- Update: Abstract: Agnieszka Korfel, Eckhard Thiel, Peter Martus, Robert Moehle, Frank Griesinger, Michael Rauch, Alexander Roeth, Bernd Hertenstein, Thomas Fischer, Thomas Hundsberger, Hans-Guenther Mergenthaler, Christian Junghanss, Tobias Birnbaum, Lars Fischer, Kristoph Jahnke, Ulrich Herrlinger, Ludwig Plasswilm, Thomas Naegele, Torsten Pietsch, Michael Weller. G-PCNSL-SG-1 randomized phase III trial of high-dose methotrexate with or without whole brain radiotherapy for primary central nervous system lymphoma: Long-term follow-up. J Clin Oncol 32:5s, 2014 (suppl; abstr 8527) link to abstract
- Update: Korfel A, Thiel E, Martus P, Möhle R, Griesinger F, Rauch M, Röth A, Hertenstein B, Fischer T, Hundsberger T, Mergenthaler HG, Junghanß C, Birnbaum T, Fischer L, Jahnke K, Herrlinger U, Roth P, Bamberg M, Pietsch T, Weller M. Randomized phase III study of whole-brain radiotherapy for primary CNS lymphoma. Neurology. 2015 Mar 24;84(12):1242-8. Epub 2015 Feb 25. link to original article PubMed
Cytarabine & Etoposide
back to top |
Regimen
Study | Evidence |
Colombat et al. 2006 | Phase II |
Treatment preceded by non-response to MVBP x 2.
- Cytarabine (Cytosar) 1000 mg/m2 IV Q12H on days 1 & 2
- Etoposide (Vepesid) 150 mg/m2 IV once per day on days 1 & 2
Two courses
Treatment followed by whole-brain irradiation.
References
- Colombat P, Lemevel A, Bertrand P, Delwail V, Rachieru P, Brion A, Berthou C, Bay JO, Delepine R, Desablens B, Camilleri-Broët S, Linassier C, Lamy T. High-dose chemotherapy with autologous stem cell transplantation as first-line therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter phase II study of the GOELAMS group. Bone Marrow Transplant. 2006 Sep;38(6):417-20. link to original article contains verified protocol PubMed
High-dose Methotrexate & Ifosfamide
back to top |
Regimen
Study | Evidence |
Fischer et al. 2008 | Retrospective |
- Methotrexate (MTX) 4000 mg/m2 IV over 4 hours once on day 1
- Ifosfamide (Ifex) 1500 to 2000 mg/m2 IV over 3 hours once per day on days 3 to 5
Supportive medications
- Mesna (Mesnex) for prophylaxis of hemorrhagic cystitis
- Folinic acid (Leucovorin) rescue starting 24 hours after start of Methotrexate (MTX) infusion
- Sodium bicarbonate via IV fluid or PO routes used for urine alkalinization to maintain urine pH of at least 8
- Check methotrexate levels 24, 48, and 72 hours after completion of methotrexate infusion.
Methotrexate (MTX) dose adjusted for creatinine clearances <100 mL/min according to the following formula:
- Dose of methotrexate = (creatinine clearance/100) x 4000 mg/m2; the paper did not specify what method was used for calculating creatinine clearance. Patients with creatinine clearance <50 mL/min were excluded from the study.
up to 8 cycles (reference did not list timing/criteria to be used for next cycle of therapy)
References
- Fischer L, Korfel A, Kiewe P, Neumann M, Jahnke K, Thiel E. Systemic high-dose methotrexate plus ifosfamide is highly effective for central nervous system (CNS) involvement of lymphoma. Ann Hematol. 2009 Feb;88(2):133-9. Epub 2008 Aug 5. link to original article contains verified protocol PubMed
Topotecan (Hycamtin)
back to top |
Regimen
Study | Evidence |
Fischer et al. 2006 | Phase II |
Voloschin et al. 2008 | Phase II, <20 pts |
- Topotecan (Hycamtin) 1.5 mg/m2 IV over 30 minutes once per day on days 1 to 5
Supportive medications:
- Voloschin et al. 2008: Ondansetron (Zofran) (dose/route not specified) prior to chemotherapy
21-day cycle x 6 to 10 cycles
References
- Fischer L, Thiel E, Klasen HA, Birkmann J, Jahnke K, Martus P, Korfel A. Prospective trial on topotecan salvage therapy in primary CNS lymphoma. Ann Oncol. 2006 Jul;17(7):1141-5. Epub 2006 Apr 7. link to original article contains verified protocol PubMed
- Voloschin AD, Betensky R, Wen PY, Hochberg F, Batchelor T. Topotecan as salvage therapy for relapsed or refractory primary central nervous system lymphoma. J Neurooncol. 2008 Jan;86(2):211-5. Epub 2007 Sep 21. link to original article contains verified protocol PubMed
Whole brain irradiation
back to top |
Regimen #1
Study | Evidence |
Thiel et al. 2010 (G-PCNSL-SG-1) | Non-randomized |
Treatment preceded by non-response to high-dose MTX x 6 before 2006 or high-dose methotrexate & ifosfamide x 6 after 2006.
- Whole-brain irradiation to 45 Gy in 1.5-Gy fractions
Regimen #2
Study | Evidence |
Colombat et al. 2006 | Phase II |
Treatment preceded by cytarabine & etoposide salvage.
- Whole-brain irradiation to 30 Gy in 1.8-Gy fractions plus 10 Gy boost to the tumor bed
Regimen #3
Study | Evidence |
Nguyen et al. 2005 | Phase II |
The authors do not clearly describe a pre-determined dosing protocol but report that the most common fraction size was 1.5 Gy.
- Median dose:
- Patients not receiving a boost: 36 Gy (range 28 to 45 Gy)
- Patients receiving a boost: 36 Gy (range 19.6 to 40 Gy) + 10 Gy (range 10 to 21.6 Gy)
References
- Nguyen PL, Chakravarti A, Finkelstein DM, Hochberg FH, Batchelor TT, Loeffler JS. Results of whole-brain radiation as salvage of methotrexate failure for immunocompetent patients with primary CNS lymphoma. J Clin Oncol. 2005 Mar 1;23(7):1507-13. link to original article contains verified protocol PubMed
- Colombat P, Lemevel A, Bertrand P, Delwail V, Rachieru P, Brion A, Berthou C, Bay JO, Delepine R, Desablens B, Camilleri-Broët S, Linassier C, Lamy T. High-dose chemotherapy with autologous stem cell transplantation as first-line therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter phase II study of the GOELAMS group. Bone Marrow Transplant. 2006 Sep;38(6):417-20. link to original article contains verified protocol PubMed
- Thiel E, Korfel A, Martus P, Kanz L, Griesinger F, Rauch M, Röth A, Hertenstein B, von Toll T, Hundsberger T, Mergenthaler HG, Leithäuser M, Birnbaum T, Fischer L, Jahnke K, Herrlinger U, Plasswilm L, Nägele T, Pietsch T, Bamberg M, Weller M. High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial. Lancet Oncol. 2010 Nov;11(11):1036-47. Epub 2010 Oct 20. link to original article contains verified protocol PubMed
- Update: Abstract: Agnieszka Korfel, Eckhard Thiel, Peter Martus, Robert Moehle, Frank Griesinger, Michael Rauch, Alexander Roeth, Bernd Hertenstein, Thomas Fischer, Thomas Hundsberger, Hans-Guenther Mergenthaler, Christian Junghanss, Tobias Birnbaum, Lars Fischer, Kristoph Jahnke, Ulrich Herrlinger, Ludwig Plasswilm, Thomas Naegele, Torsten Pietsch, Michael Weller. G-PCNSL-SG-1 randomized phase III trial of high-dose methotrexate with or without whole brain radiotherapy for primary central nervous system lymphoma: Long-term follow-up. J Clin Oncol 32:5s, 2014 (suppl; abstr 8527) link to abstract
- Update: Korfel A, Thiel E, Martus P, Möhle R, Griesinger F, Rauch M, Röth A, Hertenstein B, Fischer T, Hundsberger T, Mergenthaler HG, Junghanß C, Birnbaum T, Fischer L, Jahnke K, Herrlinger U, Roth P, Bamberg M, Pietsch T, Weller M. Randomized phase III study of whole-brain radiotherapy for primary CNS lymphoma. Neurology. 2015 Mar 24;84(12):1242-8. Epub 2015 Feb 25. link to original article PubMed