Revision as of 12:12, 15 October 2022

Back to Top

Section editor transclusions Note: these are regimens tested in biomarker-specific populations and includes gastric and gastroesophageal cancers. Please see the main gastric cancer page or the main esophageal cancer page for other regimens.

0 regimens on this page 0 variants on this page

Guidelines

CAP/ASCP/ASCO

2017: Bartley et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma PubMed

Metastatic or locally advanced disease, first-line

Capecitabine & Cisplatin (CX)

CX: Cisplatin & Xeloda (Capecitabine)
XP: Xeloda (Capecitabine) & Platinol (Cisplatin)

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Bang et al. 2010 (ToGA)	2005-2008	Phase 3 (C)	1. CF & Trastuzumab 2. CX & Trastuzumab	Inferior OS

Patients:100% adenocarcinoma (19% gastroesophageal junction, 81% gastric). 10% with ECOG of 2.

Biomarker eligibility criteria

Overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV over 2 hours once on day 1
Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14

21-day cycles

References

ToGA: Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. link to original article contains dosing details in manuscript PubMed NCT01041404

Capecitabine & Cisplatin (CX) & Trastuzumab

CX & Trastuzumab: Cisplatin, Xeloda (Capecitabine), Trastuzumab

Regimen variant #1, 80/1600

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Shah et al. 2017 (HELOISE)	2011-2015	Phase 3b (C)	CX & Trastuzumab; high-dose	Did not meet primary endpoint of OS

Patients: 79% gastric, 21% GE junction, and all patients had an ECOG of 2

Biomarker eligibility criteria

Patients had overexpression of HER2 protein by immunohistochemistry AND gene amplification by in-situ hybridization.

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV once on day 1
Capecitabine (Xeloda) 800 mg/m² PO twice per day on days 1 to 14

Targeted therapy

Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1

21-day cycle for up to 6 cycles

Subsequent treatment

Trastuzumab maintenance

Regimen variant #2, 80/2000

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Bang et al. 2010 (ToGA)	2005-2008	Phase 3 (E-RT-esc)	1. CF 2. CX	Superior OS Median OS: 13.8 vs 11.1 mo (HR 0.74, 95% CI 0.60-0.91)
Tabernero et al. 2018 (JACOB)	2013-2016	Phase 3 (C)	CX, Pertuzumab, Trastuzumab	Seems to have inferior OS Median OS: 14.2 vs 17.5 mo (HR 1.19, 95% CI 1.00-1.41)

ToGA patients: 81% gastric, 19% GE junction. 10% of patients with ECOG of 2.

Biomarker eligibility criteria

ToGA: overexpression of HER2 protein by immunohistochemistry OR gene amplification by fluorescence in-situ hybridization.

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV once on day 1
Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14

Targeted therapy

Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1

21-day cycles

References

ToGA: Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. link to original article contains dosing details in manuscript PubMed NCT01041404
HELOISE: Shah MA, Xu RH, Bang YJ, Hoff PM, Liu T, Herráez-Baranda LA, Xia F, Garg A, Shing M, Tabernero J. HELOISE: Phase IIIb randomized multicenter study comparing standard-of-care and higher-dose trastuzumab regimens combined with chemotherapy as first-line therapy in patients with human epidermal growth factor receptor 2-positive metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol. 2017 Aug 1;35(22):2558-2567. Epub 2017 Jun 2.link to original article contains dosing details in manuscript PubMed NCT01450696
JACOB: Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Cheng K, Song C, Wu H, Eng-Wong J, Kim K, Kang YK. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018 Oct;19(10):1372-1384. Epub 2018 Sep 11. link to original article contains dosing details in abstract PubMed NCT01774786

CapeOx

CapeOx: Capecitabine and Oxaliplatin

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Hecht et al. 2015 (LOGiC)	2008-2012	Phase 3 (C)	CapeOx & Lapatinib	Did not meet primary endpoint of OS Median OS: 10.5 vs 12.2 mo (HR 1.10, 95% CI 0.89-1.37)

100% adenocarcinoma histology (4% esophagus, 9% gastroesophageal junction, 87% gastric origin). 9% with ECOG PS of 2.

Biomarker eligibility criteria

HER2 positive

Chemotherapy

Capecitabine (Xeloda) 850 mg/m² PO twice per day on days 1 to 14
Oxaliplatin (Eloxatin) 130 mg/m² IV once on day 1

21-day cycle for up to 8 cycles

References

LOGiC: Hecht JR, Bang YJ, Qin SK, Chung HC, Xu JM, Park JO, Jeziorski K, Shparyk Y, Hoff PM, Sobrero A, Salman P, Li J, Protsenko SA, Wainberg ZA, Buyse M, Afenjar K, Houé V, Garcia A, Kaneko T, Huang Y, Khan-Wasti S, Santillana S, Press MF, Slamon D. Lapatinib in combination with capecitabine plus oxaliplatin in human epidermal growth factor receptor 2-positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma: TRIO-013/LOGiC--a randomized phase III trial. J Clin Oncol. 2016 Feb 10;34(5):443-51. Epub 2015 Nov 30. link to original article PubMed NCT00680901
HERIZON-GEA-01: NCT05152147

CapeOx, Pembrolizumab, Trastuzumab

CapeOx, Pembrolizumab, Trastuzumab: Capecitabine, Oxaliplatin, Pembrolizumab, Trastuzumab

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Janjigian et al. 2021 (KEYNOTE-811)	2018-2020	Phase 3 (E-RT-esc)	1. CapeOx & Trastuzumab 2. CF & Trastuzumab	Superior ORR¹

¹This is an interim secondary endpoint; primary endpoints are PFS and OS.

Biomarker eligibility criteria

HER2 positive

Chemotherapy

Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14
Oxaliplatin (Eloxatin) 130 mg/m² IV over 2 hours once on day 1

Immunotherapy

Pembrolizumab (Keytruda) 200 mg IV once on day 1

Targeted therapy

Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1

21-day cycles

References

KEYNOTE-811: Janjigian YY, Kawazoe A, Yañez P, Li N, Lonardi S, Kolesnik O, Barajas O, Bai Y, Shen L, Tang Y, Wyrwicz LS, Xu J, Shitara K, Qin S, Van Cutsem E, Tabernero J, Li L, Shah S, Bhagia P, Chung HC. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature. 2021 Dec;600(7890):727-730. Epub 2021 Dec 15. link to original article link to PMC article contains dosing details in manuscript PubMed NCT03615326

CapeOx & Trastuzumab

CapeOx & Trastuzumab: Capecitabine, Oxaliplatin, Trastuzumab

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Janjigian et al. 2021 (KEYNOTE-811)	2018-2020	Phase 3 (C)	1. CapeOx, Pembrolizumab, Trastuzumab 2. CF, Pembrolizumab, Trastuzumab	Inferior ORR¹

¹This is an interim secondary endpoint; primary endpoints are PFS and OS.
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.

Biomarker eligibility criteria

HER2 positive

Chemotherapy

Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14
Oxaliplatin (Eloxatin) 130 mg/m² IV over 2 hours once on day 1

Targeted therapy

Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1

21-day cycles

References

KEYNOTE-811: Janjigian YY, Kawazoe A, Yañez P, Li N, Lonardi S, Kolesnik O, Barajas O, Bai Y, Shen L, Tang Y, Wyrwicz LS, Xu J, Shitara K, Qin S, Van Cutsem E, Tabernero J, Li L, Shah S, Bhagia P, Chung HC. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature. 2021 Dec;600(7890):727-730. Epub 2021 Dec 15. link to original article link to PMC article contains dosing details in manuscript PubMed NCT03615326

Cisplatin & Fluorouracil (CF)

CF: Cisplatin & Fluorouracil
FP: Fluorouracil & Platinol (Cisplatin)

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Bang et al. 2010 (ToGA)	2005-2008	Phase 3 (C)	1. CF & Trastuzumab 2. CX & Trastuzumab	Inferior OS

ToGA Patients: 100% adenocarcinoma (19% gastroesophageal junction, 81% gastric). 10% with ECOG of 2.

Biomarker eligibility criteria

Overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation.

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV over 1 to 3 hours once on day 1, given first
Fluorouracil (5-FU) 800 mg/m²/day IV continuous infusion over 120 hours, started on day 1, given second (total dose per cycle: 4000 mg/m²)

21-day cycle for up to 6 cycles

References

ToGA: Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. link to original article contains dosing details in manuscript PubMed NCT01041404

Cisplatin & Fluorouracil (CF) & Trastuzumab

CF & Trastuzumab: Cisplatin, Fluorouracil, Trastuzumab

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Bang et al. 2010 (ToGA)	2005-2008	Phase 3 (E-esc)	1. CF 2. CX	Superior OS Median OS: 13.8 vs 11.1 mo (HR 0.74, 95% CI 0.60-0.91)

Patients: 100% adenocarcinoma (19% gastroesophageal junction, 81% gastric). 10% with ECOG of 2.

Biomarker eligibility criteria

Patients had overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation.

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV once on day 1
Fluorouracil (5-FU) 800 mg/m²/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m²)

Targeted therapy

Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1

21-day cycles

References

ToGA: Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. link to original article contains dosing details in manuscript PubMed NCT01041404
HERIZON-GEA-01: NCT05152147
KEYNOTE-811: NCT03615326

Metastatic or locally advanced disease, subsequent lines of therapy

Docetaxel monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Thuss-Patience et al. 2017 (GATSBY)	2012-2013	Phase 2/3 (C)	T-DM1	Did not meet primary endpoint of OS Median OS: 8.6 vs 7.9 mo (HR 0.87, 95% CI 0.66-1.15)

Note: study patients could only have been treated by one other regimen and could not have been exposed to anthracyclines Patients: 68% gastric, 32% GEJ

Biomarker eligibility criteria

HER2-positive disease

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV once on day 1

21-day cycles

References

GATSBY: Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017 May;18(5):640-653. Epub 2017 Mar 23. link to original article contains dosing details in abstract PubMed NCT01641939

Trastuzumab deruxtecan monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Shitara et al. 2020 (DESTINY-Gastric01)	2017-2019	Randomized Phase 2 (E-RT-switch-ooc)	Investigator's choice of: 1. Irinotecan 2. Paclitaxel	Superior OS Median OS: 12.5 vs 8.4 mo (HR 0.59, 95% CI 0.39-0.88)

Note: the dose is different from the FDA-approved dose for breast cancer. Patients had received a median of two prior therapies for advanced or metastatic disease (17% had received at least four prior therapies, 72% had previously received ramucirumab and 86% had received taxanes). The median time since the last administration of trastuzumab was 5.9 months in the trastuzumab deruxtecan group and 6.5 months among those in the investigator's choice group.

Biomarker eligibility criteria

HER2 over-expression

Antibody-drug conjugate therapy

Trastuzumab deruxtecan (Enhertu) 6.4 mg/kg IV once on day 1

21-day cycles

References

DESTINY-Gastric01: Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419-2430. Epub 2020 May 29. link to original article contains dosing details in manuscript PubMed NCT03329690

Irinotecan monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Shitara et al. 2020 (DESTINY-Gastric01)	2017-2019	Randomized Phase 2 (C)	Trastuzumab deruxtecan	Inferior OS

Biomarker eligibility criteria

DESTINY-Gastric01: HER2 over-expression

Chemotherapy

Irinotecan (Camptosar) 150 mg/m² IV once on day 1

14-day cycles

References

DESTINY-Gastric01: Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419-2430. Epub 2020 May 29. link to original article contains dosing details in manuscript PubMed NCT03329690

Paclitaxel monotherapy

Regimen variant #1, 80 mg/m² weekly

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Thuss-Patience et al. 2017 (GATSBY)	2012-2013	Phase 2/3 (C)	T-DM1	Did not meet primary endpoint of OS Median OS: 8.6 vs 7.9 mo (HR 0.87, 95% CI 0.66-1.15)

GATSBY included patients with GE junction malignancy (68% gastric, 32% GE junction)

Biomarker eligibility criteria

Overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation

Chemotherapy

Paclitaxel (Taxol) 80 mg/m² IV once per day on days 1, 8, 15

21-day cycles

Regimen variant #2, 80 mg/m², 3 out of 4 weeks

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Satoh et al. 2014 (TyTAN)	2007-2009	Phase 3 (C)	Lapatinib & Paclitaxel	Did not meet primary endpoint of OS Median OS: 8.9 vs 11 mo (HR 1.19, 95% CI 0.90-1.56)
Shitara et al. 2020 (DESTINY-Gastric01)	2017-2019	Randomized Phase 2 (C)	Trastuzumab deruxtecan	Inferior OS

Biomarker eligibility criteria

HER2-positive disease

Chemotherapy

Paclitaxel (Taxol) 80 mg/m² IV over 60 minutes once per day on days 1, 8, 15

28-day cycles

References

TyTAN: Satoh T, Xu RH, Chung HC, Sun GP, Doi T, Xu JM, Tsuji A, Omuro Y, Li J, Wang JW, Miwa H, Qin SK, Chung IJ, Yeh KH, Feng JF, Mukaiyama A, Kobayashi M, Ohtsu A, Bang YJ. Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: TyTAN--a randomized, phase III study. J Clin Oncol. 2014 Jul 1;32(19):2039-49. Epub 2014 May 27. link to original article contains dosing details in manuscript PubMed NCT00486954
GATSBY: Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017 May;18(5):640-653. Epub 2017 Mar 23. link to original article contains dosing details in abstract PubMed NCT01641939
DESTINY-Gastric01: Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419-2430. Epub 2020 May 29. link to original article contains dosing details in manuscript PubMed NCT03329690

Paclitaxel & Ramucirumab

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Awaiting publication (DESTINY-Gastric04)	2021-ongoing	Phase 3 (C)	Trastuzumab deruxtecan	In progress

Note: Dosing information is from CT.gov.

Targeted therapy

Ramucirumab (Cyramza) 8 mg/kg IV once per day on days 1 & 15

Chemotherapy

Paclitaxel (Taxol) 80 mg/m² IV once per day on days 1, 8, 15

28-day cycles

References

DESTINY-Gastric04: NCT04704934

@@ Line 3: / Line 3: @@
 [[#top|Back to Top]]
 </div>
-{| class="wikitable" style="text-align:center; width:100%;"
+{{#lst:Section editor transclusions|gi}}
-!colspan="4" align="center" style="color:white; font-size:125%; background-color:#de2d26"|'''Section editors'''
+<big>'''Note: these are regimens tested in biomarker-specific populations and includes gastric and gastroesophageal cancers. Please see the [[gastric cancer|main gastric cancer page]] or the [[esophageal cancer|main esophageal cancer page]] for other regimens.'''</big>
-|-
-|style="background-color:#F0F0F0; width: 15%"|[[File:SeemaNagpal.jpg|frameless|upright=0.3|center]]
-|style="width:35%" |<big>[[User:Seemanagpal|Seema Nagpal, MD]]<br>Stanford University<br>Palo Alto, CA</big>
-|style="background-color:#F0F0F0; width: 15%"|[[File:TarsheenSethi.jpg|frameless|upright=0.3|center]]
-|style="width:35%" |<big>[[User:Tarsheensethi|Tarsheen Sethi, MD, MSCI]]<br>Yale University<br>New Haven, CT</big><br>[[File:Social-twitter-icon.png|frameless|upright=0.1]] [https://twitter.com/tarsheen2 tarsheen2]
-|-
-|}
-''Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit [[CNS lymphoma - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''
 {| class="wikitable" style="float:right; margin-right: 5px;"
 |-
@@ Line 20: / Line 12: @@
 {{TOC limit|limit=3}}
 =Guidelines=
-==BSH==
+==CAP/ASCP/ASCO==
-*'''2018:''' Fox et al. [https://doi.org/10.1111/bjh.15661 Guidelines for the diagnosis and management of primary central nervous system diffuse large B-cell lymphoma]
+*'''2017:''' Bartley et al. [https://doi.org/10.1200/JCO.2016.69.4836 HER2 testing and clinical decision making in gastroesophageal adenocarcinoma] [https://pubmed.ncbi.nlm.nih.gov/28129524 PubMed]
-==EANO==
+=Metastatic or locally advanced disease, first-line=
-*'''2015:''' Hoang-Xuan et al. [http://www.zora.uzh.ch/id/eprint/114449/ Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for Neuro-Oncology]
+==Capecitabine & Cisplatin (CX) {{#subobject:c58325|Regimen=1}}==
-==ESH==
+CX: '''<u>C</u>'''isplatin & '''<u>X</u>'''eloda (Capecitabine)
-*'''2019:''' Fox et al. [https://doi.org/10.1111/bjh.15661 Guidelines for the diagnosis and management of primary central nervous system diffuse large B-cell lymphoma]
+<br>XP: '''<u>X</u>'''eloda (Capecitabine) & '''<u>P</u>'''latinol (Cisplatin)
-==[http://www.esmo.org/ ESMO]==
-*'''2016:''' Vitolo et al. [http://annonc.oxfordjournals.org/content/27/suppl_5/v91.full.pdf+html Extranodal diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/27377716 PubMed]
-==GEL/TAMO==
-*'''2016:''' Peñalver et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5286932/ Guidelines for diagnosis, prevention and management of central nervous system involvement in diffuse large B-cell lymphoma patients by the Spanish Lymphoma Group (GELTAMO)]
-==[https://www.nccn.org/ NCCN]==
-*[https://www.nccn.org/professionals/physician_gls/pdf/cns.pdf NCCN Guidelines - Central Nervous System Cancers]
-=CNS prophylaxis, systemic therapy=
-==High-dose Cytarabine monotherapy (HiDAC) {{#subobject:75c24e|Regimen=1}}==
-HiDAC: '''<u>Hi</u>'''gh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:0258f4|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/10.1093/annonc/mds621 Holte et al. 2013 (NLG LBC-04)]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-''Note: IT treatment was not part of prophylaxis, except that [[Methotrexate (MTX)]] 15 mg IT was allowed at time of diagnostic LP.''
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*[[Diffuse_large_B-cell_lymphoma#R-CHOEP-14|R-CHOEP-14]] x 8
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Cytarabine (Ara-C)]] by the following age-based criteria:
-**Younger than 60: 3000 mg/m<sup>2</sup> IV twice per day on days 1 & 2 (total dose: 12,000 mg/m<sup>2</sup>)
-**60 to 65 years: 2000 mg/m<sup>2</sup> IV twice per day on days 1 & 2 (total dose: 8000 mg/m<sup>2</sup>)
-**Older than 65: not defined
-'''21-day course'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*[[#Methotrexate_monotherapy|HD-MTX]]
-</div></div>
-===References===
-# '''NLG LBC-04:''' Holte H, Leppä S, Björkholm M, Fluge O, Jyrkkiö S, Delabie J, Sundström C, Karjalainen-Lindsberg ML, Erlanson M, Kolstad A, Fosså A, Ostenstad B, Löfvenberg E, Nordström M, Janes R, Pedersen LM, Anderson H, Jerkeman M, Eriksson M; Nordic Lymphoma Group. Dose-densified chemoimmunotherapy followed by systemic central nervous system prophylaxis for younger high-risk diffuse large B-cell/follicular grade 3 lymphoma patients: results of a phase II Nordic Lymphoma Group study. Ann Oncol. 2013 May;24(5):1385-92. Epub 2012 Dec 17. [https://doi.org/10.1093/annonc/mds621 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23247661 PubMed] NCT01502982
-==Methotrexate monotherapy {{#subobject:e89965|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:a5d109|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/10.1093/annonc/mds621 Holte et al. 2013 (NLG LBC-04)]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-''Note: IT treatment was not part of prophylaxis, except that [[Methotrexate (MTX)]] 15 mg IT was allowed at time of diagnostic LP.''
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*[[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]]
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
-====Supportive therapy====
-*[[Folinic acid (Leucovorin)]] (dose/frequency not specified) starting at 36 hours
-'''One course'''
-</div></div>
-===References===
-# '''NLG LBC-04:''' Holte H, Leppä S, Björkholm M, Fluge O, Jyrkkiö S, Delabie J, Sundström C, Karjalainen-Lindsberg ML, Erlanson M, Kolstad A, Fosså A, Ostenstad B, Löfvenberg E, Nordström M, Janes R, Pedersen LM, Anderson H, Jerkeman M, Eriksson M; Nordic Lymphoma Group. Dose-densified chemoimmunotherapy followed by systemic central nervous system prophylaxis for younger high-risk diffuse large B-cell/follicular grade 3 lymphoma patients: results of a phase II Nordic Lymphoma Group study. Ann Oncol. 2013 May;24(5):1385-92. Epub 2012 Dec 17. [https://doi.org/10.1093/annonc/mds621 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23247661 PubMed] NCT01502982
-=CNS treatment, local therapy=
-==IT Cytarabine monotherapy {{#subobject:867516|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:a436da|Variant=1}}===
+===Regimen {{#subobject:130681|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 100: / Line 27: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/jco.1999.17.10.3110 Glantz et al. 1999]
+|[https://doi.org/10.1016/S0140-6736(10)61121-X Bang et al. 2010 (ToGA)]
-|1994-1998
+|2005-2008
-|style="background-color:#1a9851"|Phase 3 (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#IT_Cytarabine_liposomal_monotherapy|IT liposomal cytarabine]]
+|1. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Trastuzumab|CF & Trastuzumab]]<br>2. [[#Capecitabine_.26_Cisplatin_.28CX.29_.26_Trastuzumab|CX & Trastuzumab]]
-|style="background-color:#d73027"|Inferior ORR
+| style="background-color:#d73027" |Inferior OS
 |-
 |}
+''Patients:100% adenocarcinoma (19% gastroesophageal junction, 81% gastric). 10% with ECOG of 2.''
+<div class="toccolours" style="background-color:#fdcdac">
+====Biomarker eligibility criteria====
+*Overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation
+</div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====CNS therapy, treatment====
+====Chemotherapy====
-*[[Cytarabine (Ara-C)]] 50 mg IT once per day on days 1, 4, 8, 11, 15, 18, 22, 25
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 2 hours once on day 1
-'''4-week course'''
+*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-</div>
+'''21-day cycles'''
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*Further therapy was given to responders; see text for details
 </div></div>
 ===References===
-# Glantz MJ, LaFollette S, Jaeckle KA, Shapiro W, Swinnen L, Rozental JR, Phuphanich S, Rogers LR, Gutheil JC, Batchelor T, Lyter D, Chamberlain M, Maria BL, Schiffer C, Bashir R, Thomas D, Cowens W, Howell SB. Randomized trial of a slow-release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis. J Clin Oncol. 1999 Oct;17(10):3110-6. [https://doi.org/10.1200/jco.1999.17.10.3110 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10506606 PubMed]
+#'''ToGA:''' Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [https://doi.org/10.1016/S0140-6736(10)61121-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20728210 PubMed] NCT01041404
-==IT Cytarabine liposomal monotherapy {{#subobject:fbf1d4|Regimen=1}}==
+==Capecitabine & Cisplatin (CX) & Trastuzumab {{#subobject:7cbb79|Regimen=1}}==
+CX & Trastuzumab: '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine), Trastuzumab
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:c43afb|Variant=1}}===
+===Regimen variant #1, 80/1600 {{#subobject:cdee6d|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/jco.1999.17.10.3110 Glantz et al. 1999]
+|[https://doi.org/10.1200/JCO.2016.71.6852 Shah et al. 2017 (HELOISE)]
-|1994-1998
+|2011-2015
-|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ic)
+| style="background-color:#1a9851" |Phase 3b (C)
-|[[#IT_Cytarabine_monotherapy_2|IT cytarabine]]
+|[[#Capecitabine_.26_Cisplatin_.28CX.29_.26_Trastuzumab|CX & Trastuzumab]]; high-dose
-|style="background-color:#1a9850"|Superior ORR
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''Patients: 79% gastric, 21% GE junction, and all patients had an ECOG of 2''
-====CNS therapy, treatment====
+<div class="toccolours" style="background-color:#fdcdac">
-*[[Cytarabine liposomal (DepoCyt)]] 50 mg IT once on day 1
+====Biomarker eligibility criteria====
-'''14-day cycle for 2 cycles'''
+Patients had overexpression of HER2 protein by immunohistochemistry AND gene amplification by in-situ hybridization.
 </div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*Further therapy was given to responders; see text for details
-</div></div>
-===References===
-# Glantz MJ, LaFollette S, Jaeckle KA, Shapiro W, Swinnen L, Rozental JR, Phuphanich S, Rogers LR, Gutheil JC, Batchelor T, Lyter D, Chamberlain M, Maria BL, Schiffer C, Bashir R, Thomas D, Cowens W, Howell SB. Randomized trial of a slow-release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis. J Clin Oncol. 1999 Oct;17(10):3110-6. [https://doi.org/10.1200/jco.1999.17.10.3110 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10506606 PubMed]
-=Upfront therapy, randomized data=
-==Cytarabine & Methotrexate (CYM) {{#subobject:eef91c|Regimen=1}}==
-CYM: '''<u>CY</u>'''tarabine & '''<u>M</u>'''ethotrexate
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:5ead03|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/S0140-6736(09)61416-1 Ferreri et al. 2009 (IELSG20)]
-|2004-2007
-|style="background-color:#1a9851"|Randomized Phase 2, >20 per arm (E-esc)
-|[[#Methotrexate_monotherapy_2|High-dose MTX]]
-|style="background-color:#91cf60"|Seems to have superior CR rate
-|-
-|rowspan=2|[https://doi.org/10.1016/S2352-3026(16)00036-3 Ferreri et al. 2016 (IELSG32)]
-|rowspan=2|2010-2014
-|rowspan=2 style="background-color:#1a9851"|Randomized Phase 2 (C)
-|1. [[#Cytarabine.2C_Methotrexate.2C_Rituximab|Cytarabine, Methotrexate, Rituximab]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of CR rate
-|-
-|2. [[#MATRix|MATRix]]
-|style="background-color:#d73027"|Inferior CR rate
-|-
-|}
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 60 minutes every 12 hours on days 2 & 3
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
-*[[Methotrexate (MTX)]] 500 mg/m<sup>2</sup> IV over 15 minutes, then 3000 mg/m<sup>2</sup> IV over 3 hours once on day 1 (total dose per cycle: 3500 mg/m<sup>2</sup>)
+*[[Capecitabine (Xeloda)]] 800 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-====Supportive therapy====
+====Targeted therapy====
-*As described in Ferreri et al. 2016:
+*[[Trastuzumab (Herceptin)]] as follows:
-*[[Levoleucovorin (Fusilev)]] 15 mg/m<sup>2</sup> IV every 6 hours for 12 doses, beginning 24 hours after the '''start''' of [[Methotrexate (MTX)]]
+**Cycle 1: 8 mg/kg IV once on day 1
-**Modifications if MTX level is high 48 hours after the '''end''' of the infusion; see paper for details
+**Cycle 2 onwards: 6 mg/kg IV once on day 1
-'''21-day cycle for 4 cycles'''
+'''21-day cycle for up to 6 cycles'''
 </div>
 <div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
-*IELSG20: [[#Whole_brain_irradiation|Whole brain irradiation]], within 4 weeks
+*Trastuzumab maintenance
-*IELSG32: [[#Whole_brain_irradiation|Whole brain irradiation]] versus [[#BCNU.2FTT.2C_then_auto_HSCT|Carmustine & Thiotepa with auto HSCT]]
+</div></div><br>
-</div></div>
-===References===
-# '''IELSG20:''' 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. 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. [https://doi.org/10.1016/S0140-6736(09)61416-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19767089 PubMed] NCT00210314
-# '''IELSG32:''' Ferreri AJ, Cwynarski K, Pulczynski E, Ponzoni M, Deckert M, Politi LS, Torri V, Fox CP, Rosée PL, Schorb E, Ambrosetti A, Roth A, Hemmaway C, Ferrari A, Linton KM, Rudà R, Binder M, Pukrop T, Balzarotti M, Fabbri A, Johnson P, Gørløv JS, Hess G, Panse J, Pisani F, Tucci A, Stilgenbauer S, Hertenstein B, Keller U, Krause SW, Levis A, Schmoll HJ, Cavalli F, Finke J, Reni M, Zucca E, Illerhaus G; International Extranodal Lymphoma Study Group. Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial. Lancet Haematol. 2016 May;3(5):e217-27. Epub 2016 Apr 6. [https://doi.org/10.1016/S2352-3026(16)00036-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27132696 PubMed] NCT01011920
-==Cytarabine, Methotrexate, Rituximab {{#subobject:a4671e|Regimen=1}}==
-R-HD-MTX/ARA-C: '''<u>R</u>'''ituximab, '''<u>H</u>'''igh-'''<u>D</u>'''ose '''<u>M</u>'''etho'''<u>T</u>'''re'''<u>X</u>'''ate, '''<u>ARA-C</u>''' (Cytarabine)
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:1c6830|Variant=1}}===
+===Regimen variant #2, 80/2000 {{#subobject:27adc6|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1200/jco.2015.61.1236 Ferreri et al. 2015 (SCNSL1)]
-|2006-2013
-|style="background-color:#91cf61"|Phase 2
-| style="background-color:#d3d3d3" |
-| style="background-color:#d3d3d3" |
 |-
-|rowspan=2|[https://doi.org/10.1016/S2352-3026(16)00036-3 Ferreri et al. 2016 (IELSG32)]
+|[https://doi.org/10.1016/S0140-6736(10)61121-X Bang et al. 2010 (ToGA)]
-|rowspan=2|2010-2014
+|2005-2008
-|rowspan=2 style="background-color:#1a9851"|Randomized Phase 2 (E-esc)
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
-|1. [[#Cytarabine_.26_Methotrexate_.28CYM.29|CYM]]
+|1. [[#Cisplatin_.26_Fluorouracil_.28CF.29_4|CF]]<br>2. [[#Capecitabine_.26_Cisplatin_.28CX.29|CX]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of CR rate
+| style="background-color:#1a9850" |Superior OS<br>Median OS: 13.8 vs 11.1 mo<br>(HR 0.74, 95% CI 0.60-0.91)
 |-
-|2. [[#MATRix|MATRix]]
+|[https://doi.org/10.1016/S1470-2045(18)30481-9 Tabernero et al. 2018 (JACOB)]
-|style="background-color:#fc8d59"|Seems to have inferior CR rate
+|2013-2016
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Capecitabine_.26_Cisplatin_.28CX.29.2C_Pertuzumab.2C_Trastuzumab_88|CX, Pertuzumab, Trastuzumab]]
+| style="background-color:#fc8d59" |Seems to have inferior OS<br>Median OS: 14.2 vs 17.5 mo<br>(HR 1.19, 95% CI 1.00-1.41)
 |-
 |}
-''Note: SCNSL1 was intended for secondary CNS lymphoma, whereas IELSG32 was intended for primary CNS lymphoma.''
+''ToGA patients: 81% gastric, 19% GE junction. 10% of patients with ECOG of 2.''
-<div class="toccolours" style="background-color:#cbd5e8">
+<div class="toccolours" style="background-color:#fdcdac">
-====Preceding treatment====
+====Biomarker eligibility criteria====
-*SCNSL1: [[#R-CHOP_88|R-CHOP]] x 1
+*ToGA: overexpression of HER2 protein by immunohistochemistry OR gene amplification by fluorescence in-situ hybridization.
 </div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 60 minutes every 12 hours on days 2 & 3
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
-*[[Methotrexate (MTX)]] 500 mg/m<sup>2</sup> IV over 15 minutes, then 3000 mg/m<sup>2</sup> IV over 3 hours once on day 1 (total dose per cycle: 3500 mg/m<sup>2</sup>)
+*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 ====Targeted therapy====
-*[[Rituximab (Rituxan)]] 375  mg/m<sup>2</sup> IV once per day on days -5 & 0
+*[[Trastuzumab (Herceptin)]] as follows:
-====CNS therapy====
+**Cycle 1: 8 mg/kg IV once on day 1
-*SCNSL1: [[Cytarabine liposomal (DepoCyt)]]
+**Cycle 2 onwards: 6 mg/kg IV once on day 1
-====Supportive therapy====
+'''21-day cycles'''
-*[[Levoleucovorin (Fusilev)]] 15 mg/m<sup>2</sup> IV every 6 hours for 12 doses, beginning 24 hours after the '''start''' of [[Methotrexate (MTX)]]
-**Modifications if MTX level is high 48 hours after the '''end''' of the infusion; see paper for details
-'''21-day cycle for 4 cycles'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*SCNSL1: Intensification phase (see paper for details)
-*IELSG 32: [[#Whole_brain_irradiation|Whole brain irradiation]] versus [[#BCNU.2FTT.2C_then_auto_HSCT|Carmustine & Thiotepa with auto HSCT]]
 </div></div>
 ===References===
-# '''SCNSL1:''' 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. [https://doi.org/10.1200/jco.2015.61.1236 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26282634 PubMed] NCT00801216
+#'''ToGA:''' Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [https://doi.org/10.1016/S0140-6736(10)61121-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20728210 PubMed] NCT01041404
-# '''IELSG32:''' Ferreri AJ, Cwynarski K, Pulczynski E, Ponzoni M, Deckert M, Politi LS, Torri V, Fox CP, Rosée PL, Schorb E, Ambrosetti A, Roth A, Hemmaway C, Ferrari A, Linton KM, Rudà R, Binder M, Pukrop T, Balzarotti M, Fabbri A, Johnson P, Gørløv JS, Hess G, Panse J, Pisani F, Tucci A, Stilgenbauer S, Hertenstein B, Keller U, Krause SW, Levis A, Schmoll HJ, Cavalli F, Finke J, Reni M, Zucca E, Illerhaus G; International Extranodal Lymphoma Study Group. Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial. Lancet Haematol. 2016 May;3(5):e217-27. Epub 2016 Apr 6. [https://doi.org/10.1016/S2352-3026(16)00036-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27132696 PubMed] NCT01011920
+#'''HELOISE:''' Shah MA, Xu RH, Bang YJ, Hoff PM, Liu T, Herráez-Baranda LA, Xia F, Garg A, Shing M, Tabernero J. HELOISE: Phase IIIb randomized multicenter study comparing standard-of-care and higher-dose trastuzumab regimens combined with chemotherapy as first-line therapy in patients with human epidermal growth factor receptor 2-positive metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol. 2017 Aug 1;35(22):2558-2567. Epub 2017 Jun 2.[https://doi.org/10.1200/JCO.2016.71.6852 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28574779 PubMed] NCT01450696
-==MATRix {{#subobject:7b7130|Regimen=1}}==
+#'''JACOB:''' Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Cheng K, Song C, Wu H, Eng-Wong J, Kim K, Kang YK. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018 Oct;19(10):1372-1384. Epub 2018 Sep 11. [https://doi.org/10.1016/S1470-2045(18)30481-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30217672 PubMed] NCT01774786
-MATRix: '''<u>M</u>'''ethotrexate, '''<u>A</u>'''ra-C (Cytarabine), '''<u>T</u>'''hiotepa, '''<u>Ri</u>'''tu'''<u>x</u>'''imab
+==CapeOx {{#subobject:c699c3|Regimen=1}}==
+CapeOx: '''<u>Cape</u>'''citabine and '''<u>Ox</u>'''aliplatin
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:278704|Variant=1}}===
+===Regimen {{#subobject:d1aac0|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
 !style="width: 20%"|Years of enrollment
@@ Line 256: / Line 136: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|rowspan=2|[https://doi.org/10.1016/S2352-3026(16)00036-3 Ferreri et al. 2016 (IELSG32)]
+|[https://doi.org/10.1200/JCO.2015.62.6598 Hecht et al. 2015 (LOGiC)]
-|rowspan=2|2010-2014
+|2008-2012
-|rowspan=2 style="background-color:#1a9851"|Randomized Phase 2 (E-esc)
+| style="background-color:#1a9851" |Phase 3 (C)
-|1. [[#Cytarabine_.26_Methotrexate_.28CYM.29|CYM]]
+|[[#CapeOx_.26_Lapatinib_99|CapeOx & Lapatinib]]
-|style="background-color:#1a9850"|Superior CR rate
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 10.5 vs 12.2 mo<br>(HR 1.10, 95% CI 0.89-1.37)
-|-
-|2. [[#Cytarabine.2C_Methotrexate.2C_Rituximab|Cytarabine, Methotrexate, Rituximab]]
-|style="background-color:#91cf60"|Seems to have superior CR rate
 |-
 |}
+''100% adenocarcinoma histology (4% esophagus, 9% gastroesophageal junction, 87% gastric origin). 9% with ECOG PS of 2.''
+<div class="toccolours" style="background-color:#fdcdac">
+====Biomarker eligibility criteria====
+*HER2 positive
+</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Methotrexate (MTX)]] 500 mg/m<sup>2</sup> IV over 15 minutes, then 3000 mg/m<sup>2</sup> IV over 3 hours once on day 1 (total dose per cycle: 3500 mg/m<sup>2</sup>)
+*[[Capecitabine (Xeloda)]] 850 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 60 minutes every 12 hours on days 2 & 3
+*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
-*[[Thiotepa (Thioplex)]] 30 mg/m<sup>2</sup> IV over 30 minutes once on day 4
+'''21-day cycle for up to 8 cycles'''
-====Targeted therapy====
-*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days -5 & 0
-====Supportive therapy====
-*[[Levoleucovorin (Fusilev)]] 15 mg/m<sup>2</sup> IV every 6 hours for 12 doses, beginning 24 hours after the '''start''' of [[Methotrexate (MTX)]]
-**Modifications if MTX level is high 48 hours after the '''end''' of the infusion; see paper for details
-'''21-day cycle for 4 cycles'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*[[#Whole_brain_irradiation|Whole brain irradiation]] versus [[#BCNU.2FTT.2C_then_auto_HSCT|Carmustine & Thiotepa with auto HSCT]]
 </div></div>
 ===References===
-# '''IELSG32:''' Ferreri AJ, Cwynarski K, Pulczynski E, Ponzoni M, Deckert M, Politi LS, Torri V, Fox CP, Rosée PL, Schorb E, Ambrosetti A, Roth A, Hemmaway C, Ferrari A, Linton KM, Rudà R, Binder M, Pukrop T, Balzarotti M, Fabbri A, Johnson P, Gørløv JS, Hess G, Panse J, Pisani F, Tucci A, Stilgenbauer S, Hertenstein B, Keller U, Krause SW, Levis A, Schmoll HJ, Cavalli F, Finke J, Reni M, Zucca E, Illerhaus G; International Extranodal Lymphoma Study Group. Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial. Lancet Haematol. 2016 May;3(5):e217-27. Epub 2016 Apr 6. [https://doi.org/10.1016/S2352-3026(16)00036-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27132696 PubMed] NCT01011920
+#'''LOGiC:''' Hecht JR, Bang YJ, Qin SK, Chung HC, Xu JM, Park JO, Jeziorski K, Shparyk Y, Hoff PM, Sobrero A, Salman P, Li J, Protsenko SA, Wainberg ZA, Buyse M, Afenjar K, Houé V, Garcia A, Kaneko T, Huang Y, Khan-Wasti S, Santillana S, Press MF, Slamon D. Lapatinib in combination with capecitabine plus oxaliplatin in human epidermal growth factor receptor 2-positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma: TRIO-013/LOGiC--a randomized phase III trial. J Clin Oncol. 2016 Feb 10;34(5):443-51. Epub 2015 Nov 30. [https://doi.org/10.1200/JCO.2015.62.6598 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26628478 PubMed] NCT00680901
-==MBVP {{#subobject:7b8320|Regimen=1}}==
+#'''HERIZON-GEA-01:''' NCT05152147
-MBVP: '''<u>M</u>'''ethotrexate, '''<u>B</u>'''CNU (Carmustine), '''<u>V</u>'''umon (Teniposide), '''<u>P</u>'''rednisone
+==CapeOx, Pembrolizumab, Trastuzumab {{#subobject:gjg8c3|Regimen=1}}==
+CapeOx, Pembrolizumab, Trastuzumab: '''<u>Cape</u>'''citabine, '''<u>Ox</u>'''aliplatin, Pembrolizumab, Trastuzumab
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:27aa04|Variant=1}}===
+===Regimen {{#subobject:gzbcc0|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
 !style="width: 20%"|Years of enrollment
@@ Line 295: / Line 168: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1016/S1470-2045(18)30747-2 Bromberg et al. 2019 (HOVON 105/ALLG NHL 24)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8959470/ Janjigian et al. 2021 (KEYNOTE-811)]
-|2010-2016
+|2018-2020
-|style="background-color:#1a9851"|Phase 3 (C)
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
-|[[#R-MBVP_99|R-MBVP]]
+|1. [[#CapeOx_.26_Trastuzumab|CapeOx & Trastuzumab]]<br>2. [[#Cisplatin_.2C_Fluorouracil_.28CF.29_.26_Trastuzumab|CF & Trastuzumab]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
+| style="background-color:#1a9850" |Superior ORR<sup>1</sup>
 |-
 |}
+''<sup>1</sup>This is an interim secondary endpoint; primary endpoints are PFS and OS.''
+<div class="toccolours" style="background-color:#fdcdac">
+====Biomarker eligibility criteria====
+*HER2 positive
+</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV once per day on days 1 & 15
+*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-*[[Carmustine (BCNU)]] 100 mg/m<sup>2</sup> IV once on day 4
+*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
-*[[Teniposide (Vumon)]] 100 mg/m<sup>2</sup> IV once per day on days 2 & 3
+====Immunotherapy====
-====Glucocorticoid therapy====
+*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
-*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 5
+====Targeted therapy====
-'''28-day cycle for 2 cycles'''
+*[[Trastuzumab (Herceptin)]] as follows:
-</div>
+**Cycle 1: 8 mg/kg IV once on day 1
-<div class="toccolours" style="background-color:#cbd5e7">
+**Cycle 2 onwards: 6 mg/kg IV once on day 1
-====Subsequent treatment====
+'''21-day cycles'''
-*Responders, all ages: [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29_2|HiDAC]] consolidation
-**Patients younger than 60 also received: [[#Whole_brain_irradiation|low-dose WBRT]]
 </div></div>
 ===References===
-# '''HOVON 105/ALLG NHL 24:''' Bromberg JEC, Issa S, Bakunina K, Minnema MC, Seute T, Durian M, Cull G, Schouten HC, Stevens WBC, Zijlstra JM, Baars JW, Nijland M, Mason KD, Beeker A, van den Bent MJ, Beijert M, Gonzales M, de Jong D, Doorduijn JK; HOVON; ALLG. Rituximab in patients with primary CNS lymphoma (HOVON 105/ALLG NHL 24): a randomised, open-label, phase 3 intergroup study. Lancet Oncol. 2019 Feb;20(2):216-228. Epub 2019 Jan 7. [https://doi.org/10.1016/S1470-2045(18)30747-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30630772 PubMed] ACTRN12610000908033
+#'''KEYNOTE-811:''' Janjigian YY, Kawazoe A, Yañez P, Li N, Lonardi S, Kolesnik O, Barajas O, Bai Y, Shen L, Tang Y, Wyrwicz LS, Xu J, Shitara K, Qin S, Van Cutsem E, Tabernero J, Li L, Shah S, Bhagia P, Chung HC. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature. 2021 Dec;600(7890):727-730. Epub 2021 Dec 15. [https://doi.org/10.1038/s41586-021-04161-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8959470/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34912120/ PubMed] NCT03615326
-## '''HRQoL analysis:''' van der Meulen M, Bakunina K, Nijland M, Minnema MC, Cull G, Stevens WBC, Baars JW, Mason KD, Beeker A, Beijert M, Taphoorn MJB, van den Bent MJ, Issa S, Doorduijn JK, Bromberg JEC, Dirven L. Health-related quality of life after chemotherapy with or without rituximab in primary central nervous system lymphoma patients: results from a randomised phase III study. Ann Oncol. 2020 Aug;31(8):1046-1055. Epub 2020 May 3. [https://doi.org/10.1016/j.annonc.2020.04.014 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32371123 PubMed]
+==CapeOx & Trastuzumab {{#subobject:gh6cc3|Regimen=1}}==
-==Methotrexate monotherapy {{#subobject:031ce9|Regimen=1}}==
+CapeOx & Trastuzumab: '''<u>Cape</u>'''citabine, '''<u>Ox</u>'''aliplatin, Trastuzumab
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 3500 mg/m<sup>2</sup> {{#subobject:8ce96f|Variant=1}}===
+===Regimen {{#subobject:d1aac0|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
 !style="width: 20%"|Years of enrollment
@@ Line 330: / Line 205: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1016/S0140-6736(09)61416-1 Ferreri et al. 2009 (IELSG20)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8959470/ Janjigian et al. 2021 (KEYNOTE-811)]
-|2004-2007
+|2018-2020
-|style="background-color:#1a9851"|Randomized Phase 2 (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Cytarabine_.26_Methotrexate_.28CYM.29|CYM]]; high-dose
+|1. [[#CapeOx.2C_Pembrolizumab.2C_Trastuzumab|CapeOx, Pembrolizumab, Trastuzumab]]<br>2. [[#Cisplatin_.2C_Fluorouracil_.28CF.29.2C_Pembrolizumab.2C_Trastuzumab_88|CF, Pembrolizumab, Trastuzumab]]
-|style="background-color:#fc8d59"|Seems to have inferior CR rate
+| style="background-color:#d73027" |Inferior ORR<sup>1</sup>
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Methotrexate (MTX)]] 500 mg/m<sup>2</sup> IV over 15 minutes, then 3000 mg/m<sup>2</sup> IV over 3 hours once on day 1 (total dose per cycle: 3500 mg/m<sup>2</sup>)
-'''21-day cycle for 4 cycles'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*[[#Whole_brain_irradiation|Whole brain irradiation]], within 4 weeks
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, 4000 mg/m<sup>2</sup> {{#subobject:dcc365|Variant=1}}===
-{| class="wikitable" 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(10)70229-1 Thiel et al. 2010 (G-PCNSL-SG-1)]
-|2000-2009
-|style="background-color:#91cf61"|Non-randomized portion of RCT
-|-
-|}
-''All patients received the same induction regimen; however, the induction regimen was changed after 2006 to [[#Ifosfamide_.26_Methotrexate|high-dose MTX & ifosfamide]].''
-====Chemotherapy====
-*[[Methotrexate (MTX)]] 4000 mg/m<sup>2</sup> IV over 4 hours once on day 1
-'''14-day cycle for 6 cycles'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*Patients with CR: [[#Whole_brain_irradiation|whole-brain irradiation]] versus [[CNS_lymphoma_-_null_regimens#Observation|no further treatment]]
-*Patients with less than CR in the WB-XRT arm: Salvage [[#Whole_brain_irradiation_2|whole-brain irradiation]]
-*Patients with less than CR in the no-WB-XRT: Salvage [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29_3|HiDAC]]
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #3, 8000 mg/m<sup>2</sup> {{#subobject:8e0230|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/10.1002/ana.20495 Herrlinger et al. 2005 (NOA-03)]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-''This was considered a negative trial by the authors and is included here for historical purposes.''
-====Chemotherapy====
-*[[Methotrexate (MTX)]] 8000 mg/m<sup>2</sup> IV over 4 hours once on day 1
-'''14-day cycle for 6 cycles'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*Patients intolerant of MTX or not achieving CR after 6 cycles: Salvage [[#Whole_brain_irradiation_2|whole-brain irradiation]] versus [[#PCV_99|PCV]]; see article for details
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #4, 8000 mg/m<sup>2</sup> with renal adjustment {{#subobject:567824|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.2003.03.036 Batchelor et al. 2003 (NABTT 96-07)]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Methotrexate (MTX)]] 8000 mg/m<sup>2</sup> IV over 4 hours once on day 1
-**The full dose of 8000 mg/m<sup>2</sup> was only given if CrCl was at least 100 mL/min/1.73m<sup>2</sup>. For CrCl less than 100 mL/min/1.73m<sup>2</sup>, the dose was reduced by the percentage reduction below 100. For example, a CrCl of 50 mL/min/1.73m<sup>2</sup> would mandate a 50% dose reduction.
-'''14-day cycle until CR or a maximum of 8 cycles'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*Patients achieving CR: [[#Methotrexate_monotherapy_2|HD-MTX]] x 2, then [[#Methotrexate_monotherapy_3|methotrexate]] maintenance
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #5, 12,000 mg/m<sup>2</sup> {{#subobject:a12fcc|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/10.1093/annonc/mdl458 Montemurro et al. 2007 (OSHO-53)]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-''This dosing was intended for patients greater than 60 years old.''
-====Chemotherapy====
-*[[Methotrexate (MTX)]] 6000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 & 10
-'''20-day course'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*Responders (CR or PR): [[#Bu.2FTT.2C_then_auto_HSCT|Bu/TT, then autologous hematopoietic stem cell transplant]]
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #6, 16,000 mg/m<sup>2</sup> {{#subobject:abcfcc|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/10.1093/annonc/mdl458 Montemurro et al. 2007 (OSHO-53)]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-''This dosing was intended for patients less than 60 years old.''
-====Chemotherapy====
-*[[Methotrexate (MTX)]] 8000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 & 10
-'''20-day course'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*Responders (CR or PR): [[#Bu.2FTT.2C_then_auto_HSCT|Bu/TT, then autologous hematopoietic stem cell transplant]]
-</div></div>
-===References===
-# '''NABTT 96-07:''' 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. [https://doi.org/10.1200/jco.2003.03.036 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12637469 PubMed]
-# '''NOA-03:''' 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. [https://doi.org/10.1002/ana.20495 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15929034 PubMed] content property of [http://hemonc.org HemOnc.org]
-# '''OSHO-53:''' 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. [https://doi.org/10.1093/annonc/mdl458 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17185743 PubMed]
-# '''IELSG20:''' 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. 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. [https://doi.org/10.1016/S0140-6736(09)61416-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19767089 PubMed] NCT00210314
-# '''G-PCNSL-SG-1:''' 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. [https://doi.org/10.1016/S1470-2045(10)70229-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20970380 PubMed] NCT00153530
-<!-- ## '''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) [http://meetinglibrary.asco.org/content/129168-144 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. [http://www.neurology.org/content/84/12/1242.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/25716362 PubMed]
-=Upfront therapy, non-randomized or retrospective data=
-==Lomustine, Methotrexate, Procarbazine {{#subobject:95c040|Regimen=1}}==
-MCP: '''<u>M</u>'''ethotrexate, '''<u>C</u>'''CNU (Lomustine), '''<u>P</u>'''rocarbazine
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:0caeaa|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/10.1093/annonc/mdn628 Illerhaus et al. 2008a]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Lomustine (CCNU)]] 110 mg/m<sup>2</sup> PO once on day 1
-*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1, 15, 30
-*[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 10
-====Supportive therapy====
-*[[Folinic acid (Leucovorin)]] 15 mg/m<sup>2</sup> (route not specified) every 6 hours beginning 24 hours after start of [[Methotrexate (MTX)]] infusion, continued until clearance
-'''45-day cycle for up to 3 cycles'''
-</div></div>
-===References===
-# Illerhaus G, Marks R, Müller F, Ihorst G, Feuerhake F, Deckert M, Ostertag C, Finke J. High-dose methotrexate combined with procarbazine and CCNU for primary CNS lymphoma in the elderly: results of a prospective pilot and phase II study. Ann Oncol. 2009 Feb;20(2):319-25. Epub 2008 Oct 26. [https://doi.org/10.1093/annonc/mdn628 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18953065 PubMed]
-==Lomustine, Methotrexate, Procarbazine, Methylprednisolone {{#subobject:c81fd|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:d3269c|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.2003.11.036 Hoang-Xuan et al. 2003 (EORTC 26952)]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-''This was the first prospective phase II trial evaluating chemotherapy alone in older patients with PCNSL.''
-====Chemotherapy====
-*[[Methotrexate (MTX)]] 1000 mg/m<sup>2</sup> IV once per day on days 1, 10, 20
-*[[Lomustine (CCNU)]] 40 mg/m<sup>2</sup> PO once on day 1
-*[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 7
-====Glucocorticoid therapy====
-*[[Methylprednisolone (Solumedrol)]] as follows:
-**Days 1 to 20: 120 mg/m<sup>2</sup> IV or PO every other day
-**Days 20 to 45: 60 mg/m<sup>2</sup> IV or PO every other day
-====CNS therapy====
-*[[Methotrexate (MTX)]] 15 mg IT (admixed with [[Cytarabine (Ara-C)]]) once per day on days 1, 5, 10, 15
-*[[Cytarabine (Ara-C)]] 40 mg IT (admixed with [[Methotrexate (MTX)]]) once per day on days 1, 5, 10, 15
-====Supportive therapy====
-*[[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'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*Patients achieving PR or CR: [[#Lomustine.2C_Methotrexate.2C_Procarbazine_2|Lomustine, methotrexate, procarbazine]] maintenance
-</div></div>
-===References===
-# '''EORTC 26952:''' Hoang-Xuan K, Taillandier L, Chinot O, Soubeyran P, Bogdhan U, Hildebrand J, Frenay M, De Beule N, Delattre JY, Baron B; [[Study_Groups#EORTC|EORTC]] 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 Organisation for Research and Treatment of Cancer Brain Tumor Group. J Clin Oncol. 2003 Jul 15;21(14):2726-31. [https://doi.org/10.1200/jco.2003.11.036 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12860951 PubMed]
-==Methotrexate, then Cytarabine {{#subobject:f24bde|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Protocol {{#subobject:1d3fff|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.2003.05.024 Abrey et al. 2003]
-|style="background-color:#91cf61"|Phase 2
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''<sup>1</sup>This is an interim secondary endpoint; primary endpoints are PFS and OS.''<br>
-====Chemotherapy, part 1====
+''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.''
-*[[Methotrexate (MTX)]] 3500 mg/m<sup>2</sup> (maximum dose of 7000 mg) IV over 2 hours once on day 1
+<div class="toccolours" style="background-color:#fdcdac">
-====Supportive therapy====
+====Biomarker eligibility criteria====
-*[[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 less than 100 nmol/L
+*HER2 positive
-'''14-day cycle for 5 cycles'''
-''Patients proceed to part two 72 hours after 5th dose of MTX or once the 5th dose MTX level has cleared:''
-====Chemotherapy, part 2====
-*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV once per day on days 1 & 2
-====Supportive therapy====
-*[[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 greater than 3000/uL
-'''1-month cycle for 2 cycles (Stem cell collection took place after the first cycle)'''
 </div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*[[#BEAM.2C_then_auto_HSCT|BEAM, then autologous hematopoietic stem cell transplant]]
-</div></div>
-===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. [https://doi.org/10.1200/jco.2003.05.024 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14615443 PubMed]
-==Methotrexate, then Cytarabine & Thiotepa {{#subobject:990369|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Protocol variant #1 {{#subobject:e9fd90|Variant=1}}===
-{| class="wikitable" 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.2006.06.2117 Illerhaus et al. 2006]
-|1998-2003
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy, part 1====
-*[[Methotrexate (MTX)]] 8000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1, 10, 20
-====Supportive therapy====
-*[[Folinic acid (Leucovorin)]] 15 mg/m<sup>2</sup> every 6 hours, beginning 24 hours after start of [[Methotrexate (MTX)]], continuing until clearance
-'''28-day course'''
-''Patients with CR, PR, or SD "with clinical improvement" after the 2nd dose of MTX proceeded to:''
-====Chemotherapy, stem cell mobilization====
-*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours once per day on days 2 & 3
-*[[Thiotepa (Thioplex)]] 40 mg/m<sup>2</sup> (route not specified) once on day 3
-'''20-day course'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*[[#BCNU.2FTT.2C_then_auto_HSCT|BCNU/TT, then autologous hematopoietic stem cell transplant]]
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Protocol variant #2 {{#subobject:92e01d|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[http://www.haematologica.org/content/93/1/147.long Illerhaus et al. 2008]
-|style="background-color:#ffffbe"|Pilot, <20 patients
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy, part 1====
-*[[Methotrexate (MTX)]] 8000 mg/m<sup>2</sup> IV over 4 hours once on day 1
-====Supportive therapy====
-*[[Folinic acid (Leucovorin)]] 15 mg/m<sup>2</sup> every 6 hours, beginning 24 hours after start of [[Methotrexate (MTX)]], continuing until clearance
-'''10-day cycle for 2 to 4 cycles, followed by:'''
-====Chemotherapy, part 2====
-*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV once per day on days 1 & 2
-*[[Thiotepa (Thioplex)]] 40 mg/m<sup>2</sup> (route not specified) once on day 2
-'''21-day cycle for 2 cycles (Stem cells are mobilized and collected after the first cycle)'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*[[#BCNU.2FTT.2C_then_auto_HSCT|BCNU/TT, then autologous hematopoietic stem cell transplant]]
-</div></div>
-===References===
-<!-- Presented in part at the 47th Annual Meeting of the American Society of Hematology, Atlanta, GA, December 10-13, 2005. -->
-# 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. [https://doi.org/10.1200/jco.2006.06.2117 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16864853 PubMed]
-## '''Update:''' Kasenda B, Schorb E, Fritsch K, Finke J, Illerhaus G. Prognosis after high-dose chemotherapy followed by autologous stem-cell transplantation as first-line treatment in primary CNS lymphoma--a long-term follow-up study. Ann Oncol. 2012 Oct;23(10):2670-5. Epub 2012 Apr 3. Erratum in: Ann Oncol. 2015 Mar;26(3):608-11. [https://doi.org/10.1093/annonc/mds059 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22473593 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. [http://www.haematologica.org/content/93/1/147.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18166803 PubMed]
-## '''Update:''' Kasenda B, Schorb E, Fritsch K, Finke J, Illerhaus G. Prognosis after high-dose chemotherapy followed by autologous stem-cell transplantation as first-line treatment in primary CNS lymphoma--a long-term follow-up study. Ann Oncol. 2012 Oct;23(10):2670-5. Epub 2012 Apr 3. Erratum in: Ann Oncol. 2015 Mar;26(3):608-11. [https://doi.org/10.1093/annonc/mds059 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22473593 PubMed]
-==Methotrexate & Rituximab {{#subobject:45f333|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:715330|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940660/ Chamberlain et al. 2010]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-''Note: the bounds as described in the paper do not account for the situation where CrCl = 60 mL/min/1.73m<sup>2</sup>.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Methotrexate (MTX)]] by the following laboratory-based criteria:
+*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-**CrCl greater than 60 mL/min/1.73m<sup>2</sup>: 8000 mg/m<sup>2</sup> IV over 6 hours once on day 1
+*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
-**CrCl less than 60 mL/min/1.73m<sup>2</sup>: 4000 mg/m<sup>2</sup> IV over 6 hours once on day 1
 ====Targeted therapy====
-*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 8
+*[[Trastuzumab (Herceptin)]] as follows:
-'''14-day cycle for 4 to 6 cycles'''
+**Cycle 1: 8 mg/kg IV once on day 1
-</div>
+**Cycle 2 onwards: 6 mg/kg IV once on day 1
-<div class="toccolours" style="background-color:#cbd5e7">
+'''21-day cycles'''
-====Subsequent treatment====
-*Patients with PR/CR: [[#Methotrexate_monotherapy_3|High-dose methotrexate]] consolidation
 </div></div>
 ===References===
-# Chamberlain MC, Johnston SK. High-dose methotrexate and rituximab with deferred radiotherapy for newly diagnosed primary B-cell CNS lymphoma. Neuro Oncol. 2010 Jul;12(7):736-44. [http://neuro-oncology.oxfordjournals.org/content/12/7/736.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940660/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20511181 PubMed]
+#'''KEYNOTE-811:''' Janjigian YY, Kawazoe A, Yañez P, Li N, Lonardi S, Kolesnik O, Barajas O, Bai Y, Shen L, Tang Y, Wyrwicz LS, Xu J, Shitara K, Qin S, Van Cutsem E, Tabernero J, Li L, Shah S, Bhagia P, Chung HC. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature. 2021 Dec;600(7890):727-730. Epub 2021 Dec 15. [https://doi.org/10.1038/s41586-021-04161-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8959470/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34912120/ PubMed] NCT03615326
-==MPV {{#subobject:245afd|Regimen=1}}==
+==Cisplatin & Fluorouracil (CF) {{#subobject:4d9936|Regimen=1}}==
-MPV: '''<u>M</u>'''ethotrexate, '''<u>P</u>'''rocarbazine, '''<u>V</u>'''incristine
+CF: '''<u>C</u>'''isplatin & '''<u>F</u>'''luorouracil
+<br>FP: '''<u>F</u>'''luorouracil & '''<u>P</u>'''latinol (Cisplatin)
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:2cb0c6|Variant=1}}===
+===Regimen {{#subobject:782e95|Variant=1}}===
-{| class="wikitable" style="width: 60%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 20%" |Study
-!style="width: 33%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-|-
+! style="width: 20%" |Comparator
-|[https://doi.org/10.1200/JCO.2000.18.17.3144 Abrey et al. 2000]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|1992-1998
-|style="background-color:#91cf61"|Non-randomized
-|-
-|[https://doi.org/10.1200/jco.2002.11.013 DeAngelis et al. 2002 (RTOG 93-10)]
-|1993-NR
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Methotrexate (MTX)]] 2500 mg/m<sup>2</sup> IV over 2 to 3 hours once on day 1
-*[[Procarbazine (Matulane)]] as follows:
-**Cycles 1, 3, 5: 100 mg/m<sup>2</sup> PO once per day on days 1 to 7
-*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once on day 1
-====CNS therapy====
-*[[Methotrexate (MTX)]] 12 mg IT once on day 8 (via Ommaya reservoir)
-====Supportive therapy====
-*[[Folinic acid (Leucovorin)]] as follows:
-**Days 2 to 4: 20 mg PO every 6 hours for 12 doses, '''beginning 24 hours after IV [[Methotrexate (MTX)]] administration'''
-**Days 8 & 9: 10 mg PO every 6 hours for 8 doses, '''beginning on the evening of IT [[Methotrexate (MTX)]] administration'''
-*[[Dexamethasone (Decadron)]] as follows:
-**Cycle 1: 16 mg PO once per day on days 1 to 7, then 12 mg PO once per day on days 8 to 14
-**Cycle 2: 8 mg PO once per day on days 1 to 7, then 6 mg PO once per day on days 8 to 14
-**Cycle 3: 4 mg PO once per day on days 1 to 7, then 2 mg PO once per day on days 8 to 14
-'''14-day cycle for 5 cycles'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*[[#Whole_brain_irradiation|Whole-brain irradiation]]
-</div></div>
-===References===
-# Abrey LE, Yahalom J, DeAngelis LM. Treatment for primary CNS lymphoma: the next step. J Clin Oncol. 2000 Sep;18(17):3144-50. [https://doi.org/10.1200/JCO.2000.18.17.3144 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10963643 PubMed]
-## '''Update:''' Gavrilovic IT, Hormigo A, Yahalom J, DeAngelis LM, Abrey LE. Long-term follow-up of high-dose methotrexate-based therapy with and without whole brain irradiation for newly diagnosed primary CNS lymphoma. J Clin Oncol. 2006 Oct 1;24(28):4570-4. [https://doi.org/10.1200/JCO.2006.06.6910 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17008697 PubMed]
-# '''RTOG 93-10:''' DeAngelis LM, Seiferheld W, Schold SC, Fisher B, Schultz CJ; Radiation Therapy Oncology Group; SWOG. 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. [https://doi.org/10.1200/jco.2002.11.013 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12488408 PubMed]
-==MT-R {{#subobject:cc7d83|Regimen=1}}==
-MT-R: '''<u>M</u>'''ethotrexate, '''<u>T</u>'''emozolomide, '''<u>R</u>'''ituximab
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1 {{#subobject:5cf6d6|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872318/ Glass et al. 2016 (RTOG 0227)]
-|style="background-color:#91cf61"|Phase 1/2
-|-
-|}
-''This is the MTD of this phase 1/2 trial; it appears that only a single dose of rituximab was given.''
-====Chemotherapy====
-*[[Methotrexate (MTX)]] 3500 mg/m<sup>2</sup> IV once on day 1
-*[[Temozolomide (Temodar)]] as follows:
-**Cycles 2 & 4: 100 mg/m<sup>2</sup> PO once per day on days 8 to 12
-====Targeted therapy====
-*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once, 3 days prior to first dose of MTX
-====Supportive therapy====
-*[[Folinic acid (Leucovorin)]] 25 mg IV every 6 hours, starting 24 hours after [[Methotrexate (MTX)]], continue until MTX level less than 100 nmol/L
-'''14-day cycle for 5 cycles'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*[[#Whole_brain_irradiation|WB-XRT]] consolidation
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2 {{#subobject:5df6e6|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753699/ Rubenstein et al. 2013 (CALGB 50202)]
+|[https://doi.org/10.1016/S0140-6736(10)61121-X Bang et al. 2010 (ToGA)]
-|style="background-color:#91cf61"|Phase 2
+|2005-2008
+| style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Trastuzumab|CF & Trastuzumab]]<br>2. [[#Capecitabine_.26_Cisplatin_.28CX.29_.26_Trastuzumab|CX & Trastuzumab]]
+| style="background-color:#d73027" |Inferior OS
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''ToGA Patients: 100% adenocarcinoma (19% gastroesophageal junction, 81% gastric). 10% with ECOG of 2.''
-====Chemotherapy====
+<div class="toccolours" style="background-color:#fdcdac">
-*[[Methotrexate (MTX)]] 8000 mg/m<sup>2</sup> IV over 4 hours once on day 1
+====Biomarker eligibility criteria====
-*[[Temozolomide (Temodar)]] as follows:
+*Overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation.
-**Cycles 1, 3, 5, 7: 150 mg/m<sup>2</sup> PO once per day on days 7 to 11
-====Targeted therapy====
-*[[Rituximab (Rituxan)]] by the following criteria:
-**B-cell PCNSL, Cycles 1 to 6: 375 mg/m<sup>2</sup> IV once on day 3
-====Supportive therapy====
-*[[Folinic acid (Leucovorin)]] 100 mg/m<sup>2</sup> IV every 6 hours, start on day 2, continue until MTX level less than 50 nmol/L
-'''14-day cycle for 7 cycles'''
 </div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*Patients achieving CR or CRu: [[#Methotrexate_.26_Temozolomide_88|Methotrexate & Temozolomide]] x 1, then [[#CYVE|CYVE]] consolidation
-</div></div>
-===References===
-# '''CALGB 50202:''' 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 [https://doi.org/10.1200/jco.2012.46.9957 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753699/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23569323 PubMed] NCT00098774
-# '''RTOG 0227:''' Glass J, Won M, Schultz CJ, Brat D, Bartlett NL, Suh JH, Werner-Wasik M, Fisher BJ, Liepman MK, Augspurger M, Bokstein F, Bovi JA, Solhjem MC, Mehta MP. Phase I and II study of induction chemotherapy with methotrexate, rituximab, and temozolomide, followed by whole-brain radiotherapy and postirradiation temozolomide for primary CNS lymphoma: NRG Oncology RTOG 0227. J Clin Oncol. 2016 May 10;34(14):1620-5. Epub 2016 Mar 28. [https://doi.org/10.1200/jco.2015.64.8634 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872318/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27022122 PubMed] NCT00068250
-==MVBP {{#subobject:891647|Regimen=1}}==
-MVBP: '''<u>M</u>'''ethotrexate, '''<u>V</u>'''P16 (Etoposide), '''<u>B</u>'''CNU (Carmustine), Methyl'''<u>P</u>'''rednisolone
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:70497b|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/10.1038/sj.bmt.1705452 Colombat et al. 2006]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV once per day on days 1 & 15
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1, '''given first'''
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once on day 2
+*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1, '''given second''' (total dose per cycle: 4000 mg/m<sup>2</sup>)
-*[[Carmustine (BCNU)]] 100 mg/m<sup>2</sup> IV once on day 3
+'''21-day cycle for up to 6 cycles'''
-====Glucocorticoid therapy====
-*[[Methylprednisolone (Solumedrol)]] 60 mg/m<sup>2</sup> (route not specified) once per day on days 1 to 5
-====Supportive therapy====
-*[[Folinic acid (Leucovorin)]] details not specified
-'''2 courses (length not specified), separated by 21 days'''
-====CNS therapy====
-*[[Methotrexate (MTX)]] 20 mg IT (admixed with [[Cytarabine (Ara-C)]] and [[Methylprednisolone (Solumedrol)]])
-*[[Cytarabine (Ara-C)]] 50 mg IT (admixed with [[Methotrexate (MTX)]] and [[Methylprednisolone (Solumedrol)]])
-*[[Methylprednisolone (Solumedrol)]] 40 mg IT (admixed with [[Cytarabine (Ara-C)]] and [[Methotrexate (MTX)]])
-'''6 doses total (timing not specified)'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*Responding patients (CR or PR): [[#Cytarabine_.26_Ifosfamide_88|cytarabine & ifosfamide]] for stem cell mobilization, then [[#BEAM.2C_then_auto_HSCT|BEAM, then autologous hematopoietic stem cell transplant]]
-*Non-responders: Salvage [[#CYVE|CYVE]]
 </div></div>
 ===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; GOELAMS. 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. [https://doi.org/10.1038/sj.bmt.1705452 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16951691 PubMed]
+#'''ToGA:''' Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [https://doi.org/10.1016/S0140-6736(10)61121-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20728210 PubMed] NCT01041404
-==Nordic Regimen, older patients {{#subobject:1778db|Regimen=1}}==
+==Cisplatin & Fluorouracil (CF) & Trastuzumab {{#subobject:ca9cd1|Regimen=1}}==
+CF & Trastuzumab: '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil, Trastuzumab
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:eb66bd|Variant=1}}===
+===Regimen {{#subobject:b2731|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://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380727/ Pulczynski et al. 2015 (NLGPCNSL)]
-|2007-2010
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-''This protocol is meant for patients aged 66-75 years.''
-====Targeted therapy, A cycles====
-*[[Rituximab (Rituxan)]] as follows:
-**Cycle 1: 375 mg/m<sup>2</sup> IV once on day 1
-====Chemotherapy, A cycles====
-*[[Methotrexate (MTX)]] as follows:
-**Cycles 1 & 4: 3000 mg/m<sup>2</sup> IV once on day 1
-*[[Ifosfamide (Ifex)]] as follows:
-**Cycle 1: 800 mg/m<sup>2</sup> IV once per day on days 2 to 5
-====Glucocorticoid therapy, A cycles====
-*[[Dexamethasone (Decadron)]] as follows:
-**Cycles 1 & 4: 10 mg/m<sup>2</sup>/day PO on days 2 to 5
-====CNS therapy, A cycles====
-*[[Cytarabine liposomal (DepoCyt)]] as follows:
-**Cycles 1 & 4: 50 mg IT once on day 2
-====Chemotherapy, B cycles====
-*[[Methotrexate (MTX)]] as follows:
-**Cycles 2 & 5: 5000 mg/m<sup>2</sup> IV once on day 1
-*[[Cyclophosphamide (Cytoxan)]] as follows:
-**Cycles 2 & 5: 150 mg/m<sup>2</sup> IV once per day on days 2 to 6
-====Glucocorticoid therapy, B cycles====
-*[[Dexamethasone (Decadron)]] as follows:
-**Cycles 2 & 5: 10 mg/m<sup>2</sup>/day PO on days 2 to 5
-====CNS therapy, B cycles====
-*[[Cytarabine liposomal (DepoCyt)]] as follows:
-**Cycles 2 & 5: 50 mg IT once on day 2
-====Glucocorticoid therapy, C cycles====
-*[[Dexamethasone (Decadron)]] as follows:
-**Cycles 3 & 6: 20 mg/m<sup>2</sup>/day PO on days 3 to 7
-====Chemotherapy, C cycles====
-*[[Cytarabine (Ara-C)]] as follows:
-**Cycles 3 & 6: 1000 mg/m<sup>2</sup> IV every 12 hours on days 1 & 2
-*[[Vindesine (Eldisine)]] as follows:
-**Cycles 3 & 6: 5 mg IV once on day 1
-'''21-day cycle for 6 cycles (A1, then B1, then C1, then A2, then B2, then C2)'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*[[#Temozolomide_monotherapy|Temozolomide]] maintenance
-</div></div>
-===References===
-# '''NLGPCNSL:''' 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; Nordic Lymphoma Group. 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. [http://www.haematologica.org/content/100/4/534.full link to original article] '''contains dosing details in manuscript''' [http://www.haematologica.org/content/haematol/suppl/2015/04/01/haematol.2014.108472.DC1/2014.108472.PULCZYNSKI_SUPPL.pdf in supplement] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380727/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25480497 PubMed] NCT01458730
-==Nordic Regimen, younger patients {{#subobject:e571ce|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Protocol {{#subobject:2874b2|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://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380727/ Pulczynski et al. 2015 (NLGPCNSL)]
-|2007-2010
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-''This protocol is meant for patients aged 18 to 65 years.''
-====Targeted therapy, A cycles====
-*[[Rituximab (Rituxan)]] as follows:
-**Cycle A1: 375 mg/m<sup>2</sup> IV once on day 1
-====Chemotherapy, A cycles====
-*[[Methotrexate (MTX)]] 5000 mg/m<sup>2</sup> IV once on day 1
-*[[Ifosfamide (Ifex)]] 800 mg/m<sup>2</sup> IV once per day on days 2 to 5
-====Glucocorticoid therapy, A cycles====
-*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup>/day PO on days 2 to 5
-====CNS therapy, A cycles====
-*[[Cytarabine liposomal (DepoCyt)]] 50 mg IT once on day 2
-====Chemotherapy, B cycles====
-*[[Methotrexate (MTX)]] 5000 mg/m<sup>2</sup> IV once on day 1
-*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
-*[[Cyclophosphamide (Cytoxan)]] 200 mg/m<sup>2</sup> IV once per day on days 2 to 5
-====Glucocorticoid therapy, B cycles====
-*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup>/day PO on days 2 to 5
-====CNS therapy, B cycles====
-*[[Cytarabine liposomal (DepoCyt)]] 50 mg IT once on day 2
-====Glucocorticoid therapy, C cycles====
-*[[Dexamethasone (Decadron)]] 20 mg/m<sup>2</sup>/day PO on days 3 to 7
-====Chemotherapy, C cycles====
-*[[Cytarabine (Ara-C)]] 1500 mg/m<sup>2</sup> IV every 12 hours on days 1 & 2
-*[[Vindesine (Eldisine)]] 5 mg IV once on day 1
-'''21-day cycle for 6 cycles (A1, then B1, then C1, then A2, then B2, then C2)'''
-</div></div>
-===References===
-# '''NLGPCNSL:''' 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; Nordic Lymphoma Group. 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. [http://www.haematologica.org/content/100/4/534.full link to original article] '''contains dosing details in manuscript''' [http://www.haematologica.org/content/haematol/suppl/2015/04/01/haematol.2014.108472.DC1/2014.108472.PULCZYNSKI_SUPPL.pdf in supplement] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380727/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25480497 PubMed] NCT01458730
-==R-MCP (CCNU) {{#subobject:58966e|Regimen=1}}==
-R-MCP: '''<u>R</u>'''ituximab, '''<u>M</u>'''ethotrexate, '''<u>C</u>'''CNU (Lomustine), '''<u>P</u>'''rocarbazine
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:6b72ea|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/10.1093/annonc/mdq712 Fritsch et al. 2011]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-''Note: this regimen should not be confused with the other R-MCP (rituximab, mitoxantrone, cyclophosphamide, prednisone) used in indolent lymphomas.''
-<div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
-*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV over 90 minutes once per day on days -6, 1, 15, 29
-====Chemotherapy====
-*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV over 4 hours once per day on days 2, 16, 30
-*[[Lomustine (CCNU)]] 110 mg/m<sup>2</sup> PO once on day 2
-*[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 2 to 11
-====Supportive therapy====
-*[[Folinic acid (Leucovorin)]] (dose/route not specified) every 6 hours beginning 24 hours after start of MTX infusion, continued for 3 days or until clearance
-'''43-day cycle for up to 3 cycles'''
-</div></div>
-===References===
-# Fritsch K, Kasenda B, Hader C, Nikkhah G, Prinz M, Haug V, Haug S, Ihorst G, Finke J, Illerhaus G. Immunochemotherapy with rituximab, methotrexate, procarbazine, and lomustine for primary CNS lymphoma (PCNSL) in the elderly. Ann Oncol. 2011 Sep;22(9):2080-5. Epub 2011 Feb 8. [https://doi.org/10.1093/annonc/mdq712 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21303800 PubMed]
-==R-MP {{#subobject:58b4a9|Regimen=1}}==
-R-MP: '''<u>R</u>'''ituximab, '''<u>M</u>'''ethotrexate, '''<u>P</u>'''rocarbazine
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:6ea131|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383936/ Fritsch et al. 2016 (PRIMAIN)]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
-*[[Rituximab (Rituxan)]] as follows:
-**Cycle 1: 375 mg/m<sup>2</sup> IV over 90 minutes once per day on days -6, 1, 15, 29
-**Cycles 2 & 3: 375 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1, 15, 29
-====Chemotherapy====
-*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV over 4 hours once per day on days 2, 16, 30
-*[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 2 to 11
-'''42-day cycle for 3 cycles'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*[[#Procarbazine_monotherapy|Procarbazine]] maintenance
-</div></div>
-===References===
-# '''PRIMAIN:''' Fritsch K, Kasenda B, Schorb E, Hau P, Bloehdorn J, Möhle R, Löw S, Binder M, Atta J, Keller U, Wolf HH, Krause SW, Heß G, Naumann R, Sasse S, Hirt C, Lamprecht M, Martens U, Morgner A, Panse J, Frickhofen N, Röth A, Hader C, Deckert M, Fricker H, Ihorst G, Finke J, Illerhaus G. High-dose methotrexate-based immuno-chemotherapy for elderly primary CNS lymphoma patients (PRIMAIN study). Leukemia. 2017 Apr;31(4):846-852. Epub 2016 Nov 15. [https://doi.org/10.1038/leu.2016.334 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383936/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27843136 PubMed] NCT00989352
-==R-MPV {{#subobject:5ca49d|Regimen=1}}==
-R-MPV: '''<u>R</u>'''ituximab, '''<u>M</u>'''ethotrexate, '''<u>P</u>'''rocarbazine, '''<u>V</u>'''incristine
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:ac140a|Variant=1}}===
-{| class="wikitable" 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.2007.12.5062 Shah et al. 2007 (MSK 01-146)]
-|2002-2005
-|style="background-color:#91cf61"|Phase 2
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342354/ Omuro et al. 2015 (MSK 04-129)]
-|2005-2011
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
-*[[Rituximab (Rituxan)]] 500 mg/m<sup>2</sup> IV over 5 hours once on day 1
-====Chemotherapy====
-*[[Methotrexate (MTX)]] 3500 mg/m<sup>2</sup> IV over 2 hours once on day 2
-*[[Procarbazine (Matulane)]] as follows:
-**Odd cycles: 100 mg/m<sup>2</sup> PO once per day on days 1 to 7
-*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once on day 2
-====CNS therapy====
-*''(only described in MSK 01-146)''
-*[[Methotrexate (MTX)]] 12 mg IT (via Ommaya) once sometime between day 5 and 12 (for patients with positive CSF cytology)
-====Supportive therapy====
-*[[Folinic acid (Leucovorin)]] 20 to 25 mg every 6 hours for at least 72 hours or until serum MTX level less than 100 nmol/L, beginning 24 hours after IV [[Methotrexate (MTX)]] administration
-'''14-day cycle for 5 to 7 cycles'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*MSK 01-146: followed in 3 to 5 weeks by [[#Whole_brain_irradiation|whole-brain irradiation]]
-*MSK 04-129: [[#Bu.2FTT.2FCy.2C_then_auto_HSCT|Bu/TT/Cy, then autologous hematopoietic stem cell transplant]], after 5 cycles if CR achieved, or after 7 cycles for PR/CR at that time
-</div></div>
-===References===
-# '''MSK 01-146:''' 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. [https://doi.org/10.1200/jco.2007.12.5062 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17947720 PubMed] NCT00594815
-## '''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. [https://doi.org/10.1200/jco.2013.50.4910 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5569679/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24101038 PubMed]
-# '''MSK 04-129:''' 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. [http://www.bloodjournal.org/content/125/9/1403 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342354/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25568347 PubMed] NCT00596154
-=Consolidation and/or maintenance after upfront therapy=
-==BCNU/TT, then auto HSCT {{#subobject:a7b7ae|Regimen=1}}==
-BCNU/TT: '''<u>BCNU</u>''' (Carmustine), '''<u>T</u>'''hio'''<u>T</u>'''epa
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1 {{#subobject:81ede7|Variant=1}}===
-{| class="wikitable" 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.2006.06.2117 Illerhaus et al. 2006]
-|1998-2003
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-''Note that the day count starts from the very beginning of treatment.''
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*[[#Methotrexate.2C_then_Cytarabine_.26_Thiotepa|High-dose methotrexate, then Ara-C & Thiotepa]]
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Carmustine (BCNU)]] 400 mg/m<sup>2</sup> IV once on day 50
-*[[Thiotepa (Thioplex)]] 5 mg/kg (route not specified) once per day on days 51 & 52
-====Supportive therapy====
-*[[:Category:Granulocyte_colony-stimulating_factors|Granulocyte colony-stimulating factor]] starting on day 61, continued until WBC greater than 1 x 10<sup>9</sup>/L for 3 days
-*"Standard supportive measures were taken according to institutional guidelines."
-'''Stem cells re-infused on day 56'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*[[#Whole_brain_irradiation|Whole-brain irradiation]]
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2 {{#subobject:769950|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[http://www.haematologica.org/content/93/1/147.long Illerhaus et al. 2008]
-|style="background-color:#ffffbe"|Pilot, <20 patients
-|-
-|}
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*[[#Methotrexate.2C_then_Cytarabine_.26_Thiotepa|High-dose methotrexate, then Ara-C & Thiotepa]]
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Carmustine (BCNU)]] 400 mg/m<sup>2</sup> IV once on day 1
-*[[Thiotepa (Thioplex)]] 5 mg/kg (route not specified) twice per day on days 2 & 3
-'''Stem cells re-infused on day 7'''
-</div></div>
-===References===
-<!-- Presented in part at the 47th Annual Meeting of the American Society of Hematology, Atlanta, GA, December 10-13, 2005. -->
-# 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. [https://doi.org/10.1200/jco.2006.06.2117 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16864853 PubMed]
-## '''Update:''' Kasenda B, Schorb E, Fritsch K, Finke J, Illerhaus G. Prognosis after high-dose chemotherapy followed by autologous stem-cell transplantation as first-line treatment in primary CNS lymphoma--a long-term follow-up study. Ann Oncol. 2012 Oct;23(10):2670-5. Epub 2012 Apr 3. Erratum in: Ann Oncol. 2015 Mar;26(3):608-11. [https://doi.org/10.1093/annonc/mds059 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22473593 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. [http://www.haematologica.org/content/93/1/147.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18166803 PubMed]
-## '''Update:''' Kasenda B, Schorb E, Fritsch K, Finke J, Illerhaus G. Prognosis after high-dose chemotherapy followed by autologous stem-cell transplantation as first-line treatment in primary CNS lymphoma--a long-term follow-up study. Ann Oncol. 2012 Oct;23(10):2670-5. Epub 2012 Apr 3. Erratum in: Ann Oncol. 2015 Mar;26(3):608-11. [https://doi.org/10.1093/annonc/mds059 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22473593 PubMed]
-# '''IELSG32:''' Ferreri AJ, Cwynarski K, Pulczynski E, Ponzoni M, Deckert M, Politi LS, Torri V, Fox CP, Rosée PL, Schorb E, Ambrosetti A, Roth A, Hemmaway C, Ferrari A, Linton KM, Rudà R, Binder M, Pukrop T, Balzarotti M, Fabbri A, Johnson P, Gørløv JS, Hess G, Panse J, Pisani F, Tucci A, Stilgenbauer S, Hertenstein B, Keller U, Krause SW, Levis A, Schmoll HJ, Cavalli F, Finke J, Reni M, Zucca E, Illerhaus G; International Extranodal Lymphoma Study Group. Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial. Lancet Haematol. 2016 May;3(5):e217-27. Epub 2016 Apr 6. [https://doi.org/10.1016/S2352-3026(16)00036-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27132696 PubMed] NCT01011920
-## '''Update:''' Ferreri AJM, Cwynarski K, Pulczynski E, Fox CP, Schorb E, La Rosée P, Binder M, Fabbri A, Torri V, Minacapelli E, Falautano M, Ilariucci F, Ambrosetti A, Roth A, Hemmaway C, Johnson P, Linton KM, Pukrop T, Sønderskov Gørløv J, Balzarotti M, Hess G, Keller U, Stilgenbauer S, Panse J, Tucci A, Orsucci L, Pisani F, Levis A, Krause SW, Schmoll HJ, Hertenstein B, Rummel M, Smith J, Pfreundschuh M, Cabras G, Angrilli F, Ponzoni M, Deckert M, Politi LS, Finke J, Reni M, Cavalli F, Zucca E, Illerhaus G; International Extranodal Lymphoma Study Group. Whole-brain radiotherapy or autologous stem-cell transplantation as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in patients with primary CNS lymphoma: results of the second randomisation of the International Extranodal Lymphoma Study Group-32 phase 2 trial. Lancet Haematol. 2017 Nov;4(11):e510-e523. Epub 2017 Oct 17. [https://doi.org/10.1016/S2352-3026(17)30174-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29054815 PubMed]
-==BEAM, then auto HSCT {{#subobject:c9216e|Regimen=1}}==
-BEAM: '''<u>B</u>'''iCNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1 {{#subobject:bbc83f|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/10.1038/sj.bmt.1705452 Colombat et al. 2006]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*[[#MVBP|MVBP]] x 2
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day 1
-*[[Etoposide (Vepesid)]] 200 mg/m<sup>2</sup> IV once per day on days 2 to 5
-*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days 2 to 5
-*[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day 6
-'''Day of transplant is not specified'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*[[#Whole_brain_irradiation|Whole-brain irradiation]]
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2 {{#subobject:5bf047|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.2003.05.024 Abrey et al. 2003]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*[[#Methotrexate.2C_then_Cytarabine|Methotrexate, then Cytarabine]]
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day -7
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV every 12 hours on days -6 to -3
-*[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup> IV every 12 hours on days -6 to -3
-*[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day -2
-====Supportive therapy====
-*[[Filgrastim (Neupogen)]] 5 mcg/kg SC every 12 hours, starting on day +1 and continued until ANC greater than 1000/uL for 3 days or greater than 10,000/uL for 1 day
-'''Stem cells reinfused on day 0'''
-</div></div>
-===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. [https://doi.org/10.1200/jco.2003.05.024 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14615443 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; GOELAMS. 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. [https://doi.org/10.1038/sj.bmt.1705452 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16951691 PubMed]
-==Bu/TT, then auto HSCT {{#subobject:e04a91|Regimen=1}}==
-Bu/TT: '''<u>Bu</u>'''sulfan, '''<u>T</u>'''hio'''<u>T</u>'''epa
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:df1bb4|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/10.1093/annonc/mdl458 Montemurro et al. 2007 (OSHO-53)]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*[[#Methotrexate_monotherapy_2|High-dose methotrexate]] x 2
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[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'''
-</div></div>
-===References===
-# '''OSHO-53:''' 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. [https://doi.org/10.1093/annonc/mdl458 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17185743 PubMed]
-==Bu/TT/Cy, then auto HSCT {{#subobject:e04a91|Regimen=1}}==
-Bu/TT/Cy: '''<u>Bu</u>'''sulfan, '''<u>T</u>'''hio'''<u>T</u>'''epa, '''<u>Cy</u>'''clophosphamide
-<br>TBC: '''<u>T</u>'''hiotepa, '''<u>B</u>'''usulfan, '''<u>C</u>'''yclophosphamide
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:df1bb4|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342354/ Omuro et al. 2015 (MSK 04-129)]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*[[#R-MPV|R-MPV]]
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Busulfan (Myleran)]] 3.2 mg/kg IV once per day on days -6, -5, and -4
-*[[Thiotepa (Thioplex)]] 250 mg/m<sup>2</sup> 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'''
-</div></div>
-===References===
-# '''MSK 04-129:''' 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. [http://www.bloodjournal.org/content/125/9/1403 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342354/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25568347 PubMed] NCT00596154
-==High-dose Cytarabine monotherapy (HiDAC) {{#subobject:25959d|Regimen=1}}==
-HiDAC: '''<u>Hi</u>'''gh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:4d5aee|Variant=1}}===
-{| class="wikitable" 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.2000.18.17.3144 Abrey et al. 2000]
-|1992-1998
-|style="background-color:#91cf61"|Non-randomized
-|-
-|[https://doi.org/10.1200/jco.2002.11.013 DeAngelis et al. 2002 (RTOG 93-10)]
-|1993-NR
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-''Time interval of cycles is not explicitly described and is derived from Table 1 in DeAngelis et al. 2002.''
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*[[#Whole_brain_irradiation|Whole-brain irradiation]] x 45 Gy
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 & 2
-'''21-day cycle for 2 cycles'''
-</div></div>
-===References===
-# Abrey LE, Yahalom J, DeAngelis LM. Treatment for primary CNS lymphoma: the next step. J Clin Oncol. 2000 Sep;18(17):3144-50. [https://doi.org/10.1200/JCO.2000.18.17.3144 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10963643 PubMed]
-## '''Update:''' Gavrilovic IT, Hormigo A, Yahalom J, DeAngelis LM, Abrey LE. Long-term follow-up of high-dose methotrexate-based therapy with and without whole brain irradiation for newly diagnosed primary CNS lymphoma. J Clin Oncol. 2006 Oct 1;24(28):4570-4. [https://doi.org/10.1200/JCO.2006.06.6910 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17008697 PubMed]
-# '''RTOG 93-10:''' DeAngelis LM, Seiferheld W, Schold SC, Fisher B, Schultz CJ; Radiation Therapy Oncology Group; SWOG. 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. [https://doi.org/10.1200/jco.2002.11.013 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12488408 PubMed]
-==CYVE {{#subobject:b2c919|Regimen=1}}==
-CYVE: '''<u>CY</u>'''tarabine & '''<u>VE</u>'''pesid (Etoposide)
-<br>EA: '''<u>E</u>'''toposide & '''<u>A</u>'''ra-C (Cytarabine)
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:4df5e6|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753699/ Rubenstein et al. 2013 (CALGB 50202)]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*[[#MT-R|MT-R]] induction
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 2 hours every 12 hours on days 1 to 4 (total dose: 16,000 mg/m<sup>2</sup>)
-*[[Etoposide (Vepesid)]] 10 mg/kg/day IV continuous infusion over 96 hours, started on day 1 (total dose: 40 mg/kg)
-'''4-day course'''
-</div></div>
-===References===
-# '''CALGB 50202:''' 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 [https://doi.org/10.1200/jco.2012.46.9957 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753699/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23569323 PubMed] NCT00098774
-==Lomustine, Methotrexate, Procarbazine {{#subobject:7f4fbe|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:156623|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.2003.11.036 Hoang-Xuan et al. 2003 (EORTC 26952)]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*[[#Lomustine.2C_Methotrexate.2C_Procarbazine.2C_Methylprednisolone.2C|Lomustine, Methotrexate, Procarbazine, Methylprednisolone]] induction
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Methotrexate (MTX)]] 1000 mg/m<sup>2</sup> IV once on day 1
-*[[Lomustine (CCNU)]] 40 mg/m<sup>2</sup> PO once on day 1
-*[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 7
-====CNS therapy====
-*[[Methotrexate (MTX)]] 15 mg IT (admixed with [[Cytarabine (Ara-C)]]) once on day 1
-*[[Cytarabine (Ara-C)]] 40 mg IT (admixed with [[Methotrexate (MTX)]]) once on day 1
-====Supportive therapy====
-*[[Folinic acid (Leucovorin)]] 25 mg PO every 6 hours for 3 days, initiated 24 hours after IV [[Methotrexate (MTX)]] administration
-'''42-day cycle for 5 cycles'''
-</div></div>
-===References===
-# Hoang-Xuan K, Taillandier L, Chinot O, Soubeyran P, Bogdhan U, Hildebrand J, Frenay M, De Beule N, Delattre JY, Baron B; [[Study_Groups#EORTC|EORTC]] 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 Organisation for Research and Treatment of Cancer Brain Tumor Group. J Clin Oncol. 2003 Jul 15;21(14):2726-31. [https://doi.org/10.1200/jco.2003.11.036 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12860951 PubMed]
-==Methotrexate monotherapy {{#subobject:66ffbb|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1 {{#subobject:f64ee1|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940660/ Chamberlain et al. 2010]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-''Note: the bounds as described in the paper do not account for the situation where CrCl = 60 mL/min/1.73m<sup>2</sup>.''
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*[[#Methotrexate_.26_Rituximab|High-dose methotrexate & Rituximab]]
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Methotrexate (MTX)]] by the following laboratory-based criteria:
-**CrCl greater than 60 mL/min/1.73m<sup>2</sup>: 8000 mg/m<sup>2</sup> IV over 6 hours once on day 1
-**CrCl less than 60 mL/min/1.73m<sup>2</sup>: 4000 mg/m<sup>2</sup> IV over 6 hours once on day 1
-'''28-day cycle for 4 cycles'''
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2 {{#subobject:c0f639|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.2003.03.036 Batchelor et al. 2003 (NABTT 96-07)]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*[[#Methotrexate_monotherapy_2|High-dose methotrexate]] induction
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Methotrexate (MTX)]] 8000 mg/m<sup>2</sup> IV over 4 hours once on day 1
-**The full dose of 8000 mg/m<sup>2</sup> was only given if CrCl was at least 100 mL/min/1.73m<sup>2</sup>. For CrCl less than 100 mL/min/1.73m<sup>2</sup>, the dose was reduced by the percentage reduction below 100. For example, a CrCl of 50 mL/min/1.73m<sup>2</sup> would mandate a 50% dose reduction.
-'''28-day cycle for 11 cycles'''
-</div></div>
-===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. [https://doi.org/10.1200/jco.2003.03.036 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12637469 PubMed]
-# Chamberlain MC, Johnston SK. High-dose methotrexate and rituximab with deferred radiotherapy for newly diagnosed primary B-cell CNS lymphoma. Neuro Oncol. 2010 Jul;12(7):736-44. [http://neuro-oncology.oxfordjournals.org/content/12/7/736.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940660/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20511181 PubMed]
-==Procarbazine monotherapy {{#subobject:37e11d|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:13bae4|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383936/ Fritsch et al. 2016 (PRIMAIN)]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*[[#R-MP|R-MP]] x 3
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Procarbazine (Matulane)]] 100 mg PO once per day on days 1 to 5
-'''28-day cycle for 6 cycles'''
-</div></div>
-===References===
-# '''PRIMAIN:''' Fritsch K, Kasenda B, Schorb E, Hau P, Bloehdorn J, Möhle R, Löw S, Binder M, Atta J, Keller U, Wolf HH, Krause SW, Heß G, Naumann R, Sasse S, Hirt C, Lamprecht M, Martens U, Morgner A, Panse J, Frickhofen N, Röth A, Hader C, Deckert M, Fricker H, Ihorst G, Finke J, Illerhaus G. High-dose methotrexate-based immuno-chemotherapy for elderly primary CNS lymphoma patients (PRIMAIN study). Leukemia. 2017 Apr;31(4):846-852. Epub 2016 Nov 15. [https://doi.org/10.1038/leu.2016.334 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383936/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27843136 PubMed] NCT00989352
-==Temozolomide monotherapy {{#subobject:5c7608|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1 {{#subobject:5cf6d6|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872318/ Glass et al. 2016 (RTOG 0227)]
-|style="background-color:#91cf61"|Phase 1/2
-|-
-|}
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*[[#Whole_brain_irradiation|WB-XRT]] consolidation
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Temozolomide (Temodar)]] as follows:
-**Week 14: 200 mg/m<sup>2</sup> PO once per day for 5 days (150 mg/m<sup>2</sup> allowed)
-**Weeks 18, 22, 26, 30, 34, 38, 42, 46, 50: 200 mg/m<sup>2</sup> PO once per day for 5 days
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2 {{#subobject:084bc7|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380727/ Pulczynski et al. 2015 (NLGPCNSL)]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*[[#Nordic_Regimen.2C_older_patients|Nordic Regimen for older patients]]
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Temozolomide (Temodar)]] 150 mg/m<sup>2</sup>/day PO on days 1 to 5
-'''28-day cycle for up to 13 cycles (1 year)'''
-</div></div>
-===References===
-# '''NLGPCNSL:''' 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; Nordic Lymphoma Group. 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. [http://www.haematologica.org/content/100/4/534.full link to original article] '''contains dosing details in supplement''' [http://www.haematologica.org/content/haematol/suppl/2015/04/01/haematol.2014.108472.DC1/2014.108472.PULCZYNSKI_SUPPL.pdf link to supplement] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380727/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25480497 PubMed] NCT01458730
-# '''RTOG 0227:''' Glass J, Won M, Schultz CJ, Brat D, Bartlett NL, Suh JH, Werner-Wasik M, Fisher BJ, Liepman MK, Augspurger M, Bokstein F, Bovi JA, Solhjem MC, Mehta MP. Phase I and II study of induction chemotherapy with methotrexate, rituximab, and temozolomide, followed by whole-brain radiotherapy and postirradiation temozolomide for primary CNS lymphoma: NRG Oncology RTOG 0227. J Clin Oncol. 2016 May 10;34(14):1620-5. Epub 2016 Mar 28. [https://doi.org/10.1200/jco.2015.64.8634 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872318/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27022122 PubMed] NCT00068250
-==Whole brain irradiation {{#subobject:6115dc|Regimen=1}}==
-WBRT: '''<u>W</u>'''hole-'''<u>B</u>'''rain '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 23.4 Gy {{#subobject:a6ae7a|Variant=1}}===
-{| class="wikitable" 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.2007.12.5062 Shah et al. 2007 (MSK 01-146)]
-|2002-2005
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*[[#R-MPV|R-MPV]] x 5 to 7 cycles, with complete response
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Radiotherapy====
-*[[External_beam_radiotherapy|Whole-brain irradiation]] to 23.4 Gy in 1.80 Gy fractions
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, 30 Gy {{#subobject:8ca014|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/10.1038/sj.bmt.1705452 Colombat et al. 2006]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*[[#BEAM.2C_then_auto_HSCT|BEAM, then autologous hematopoietic stem cell transplant]], with complete response
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Radiotherapy====
-*[[External_beam_radiotherapy|Whole-brain irradiation]] to 30 Gy in 1.80 Gy fractions
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #3, 30 Gy + 10 Gy boost {{#subobject:b8264a|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/10.1038/sj.bmt.1705452 Colombat et al. 2006]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*[[#BEAM.2C_then_auto_HSCT|BEAM, then autologous hematopoietic stem cell transplant]], with partial response
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Radiotherapy====
-*[[External_beam_radiotherapy|Whole-brain irradiation]] to 30 Gy in 1.80 Gy fractions plus 10 Gy boost to the tumor bed
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #4, 36 Gy {{#subobject:d477fd|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 1,387: / Line 273: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872318/ Glass et al. 2016 (RTOG 0227)]
+|[https://doi.org/10.1016/S0140-6736(10)61121-X Bang et al. 2010 (ToGA)]
-|NR
+|2005-2008
-|style="background-color:#91cf61"|Phase 1/2
+| style="background-color:#1a9851" |Phase 3 (E-esc)
-|style="background-color:#d3d3d3"|
+|1. [[#Cisplatin_.26_Fluorouracil_.28CF.29_4|CF]]<br>2. [[#Capecitabine_.26_Cisplatin_.28CX.29|CX]]
-|style="background-color:#d3d3d3"|
+| style="background-color:#1a9850" |Superior OS<br>Median OS: 13.8 vs 11.1 mo<br>(HR 0.74, 95% CI 0.60-0.91)
-|-
-|[https://doi.org/10.1016/S2352-3026(16)00036-3 Ferreri et al. 2016 (IELSG32)]
-|2010-2014
-|style="background-color:#1a9851"|Randomized Phase 2 (C)
-|[[#BCNU.2FTT.2C_then_auto_HSCT|BCNU/TT, then auto HSCT]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS24<sup>1</sup>
 |-
 |}
-''<sup>1</sup>Reported efficacy for IELSG32 is based on the 2017 update.''
+''Patients: 100% adenocarcinoma (19% gastroesophageal junction, 81% gastric). 10% with ECOG of 2.''
-<div class="toccolours" style="background-color:#cbd5e8">
+<div class="toccolours" style="background-color:#fdcdac">
-====Preceding treatment====
+====Biomarker eligibility criteria====
-*RTOG 0227: [[#MT-R|MT-R]] induction
+*Patients had overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation.
-*IELSG32: [[#Cytarabine_.26_Methotrexate_.28CYM.29|CYM]] versus [[#Cytarabine.2C_Methotrexate.2C_Rituximab|Cytarabine, MTX, Rituximab]] versus [[#MATRix|MATRix]] induction, with complete response
 </div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Radiotherapy====
+====Chemotherapy====
-*[[External_beam_radiotherapy|Whole-brain irradiation]] to 36 Gy by the following study-specific criteria:
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
-**RTOG 0227: 1.2 Gy twice per day fractions on weeks 11 to 13
+*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
-**IELSG32: 1.80 Gy fractions
+====Targeted therapy====
-</div>
+*[[Trastuzumab (Herceptin)]] as follows:
-<div class="toccolours" style="background-color:#cbd5e7">
+**Cycle 1: 8 mg/kg IV once on day 1
-====Subsequent treatment====
+**Cycle 2 onwards: 6 mg/kg IV once on day 1
-*RTOG 0227: [[#Temozolomide_monotherapy|Temozolomide]] consolidation
+'''21-day cycles'''
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #5, 36 Gy + 9 Gy boost {{#subobject:d377ed|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/S0140-6736(09)61416-1 Ferreri et al. 2009 (IELSG20)]
-|2004-2007
-|style="background-color:#91cf61"|Non-randomized portion of phase 2 RCT
-|style="background-color:#d3d3d3"|
-|style="background-color:#d3d3d3"|
-|-
-|[https://doi.org/10.1016/S2352-3026(16)00036-3 Ferreri et al. 2016 (IELSG32)]
-|2010-2014
-|style="background-color:#1a9851"|Randomized Phase 2 (C)
-|[[#BCNU.2FTT.2C_then_auto_HSCT|BCNU/TT, then auto HSCT]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS24<sup>1</sup>
-|-
-|}
-''<sup>1</sup>Reported efficacy for IELSG32 is based on the 2017 update.''
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*IELSG20: [[#Methotrexate_monotherapy_2|High-dose methotrexate]] x 4 versus [[#Cytarabine_.26_Methotrexate_.28CYM.29|High-dose CYM]] x 4, with any response
-*IELSG32: [[#Cytarabine_.26_Methotrexate_.28CYM.29|CYM]] versus [[#Cytarabine.2C_Methotrexate.2C_Rituximab|Cytarabine, MTX, Rituximab]] versus [[#MATRix|MATRix]] induction, with partial response
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Radiotherapy====
-*[[External_beam_radiotherapy|Whole-brain irradiation]] to 36 Gy in 1.80 Gy fractions plus 9 Gy boost to the tumor bed
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #6, 40 Gy + 9 Gy boost {{#subobject:d662c5|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(09)61416-1 Ferreri et al. 2009 (IELSG20)]
-|2004-2007
-|style="background-color:#91cf61"|Non-randomized portion of phase 2 RCT
-|-
-|}
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*[[#Methotrexate_monotherapy_2|High-dose methotrexate]] x 4 versus [[#Cytarabine_.26_Methotrexate_.28CYM.29|High-dose CYM]] x 4, with stable or progressive disease
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Radiotherapy====
-*[[External_beam_radiotherapy|Whole-brain irradiation]] to 40 Gy in 1.80 Gy fractions plus 9 Gy boost to the tumor bed
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #7, 45 Gy {{#subobject:1475db|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.2000.18.17.3144 Abrey et al. 2000]
-|1992-1998
-|style="background-color:#91cf61"|Non-randomized
-|style="background-color:#d3d3d3"|
-|style="background-color:#d3d3d3"|
-|-
-|[https://doi.org/10.1200/jco.2002.11.013 DeAngelis et al. 2002 (RTOG 93-10)]
-|1993-NR
-|style="background-color:#91cf61"|Phase 2
-|style="background-color:#d3d3d3"|
-|style="background-color:#d3d3d3"|
-|-
-|[https://doi.org/10.1200/jco.2006.06.2117 Illerhaus et al. 2006]
-|1998-2003
-|style="background-color:#91cf61"|Phase 2
-|style="background-color:#d3d3d3"|
-|style="background-color:#d3d3d3"|
-|-
-|[https://doi.org/10.1016/S1470-2045(10)70229-1 Thiel et al. 2010 (G-PCNSL-SG-1)]
-|2000-2009
-|style="background-color:#1a9851"|Phase 3 (E-esc)
-|[[CNS_lymphoma_-_null_regimens#Observation|No further treatment]]
-| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
-|-
-|[https://doi.org/10.1200/jco.2007.12.5062 Shah et al. 2007 (MSK 01-146)]
-|2002-2005
-|style="background-color:#91cf61"|Phase 2
-|style="background-color:#d3d3d3"|
-|style="background-color:#d3d3d3"|
-|-
-|}
-''Note that the day count in Illerhaus et al. 2006 starts from the very beginning of treatment.''
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*Abrey et al. 2000 & RTOG 93-10: [[#MPV|MPV]] x 5
-*Illerhaus et al. 2006: [[#BCNU.2FTT.2C_then_auto_HSCT|BCNU/TT, then autologous hematopoietic stem cell transplant]], with complete response
-*Shaw et al. 2007: [[#R-MPV|R-MPV]] x 5 to 7 cycles, without complete response
-*G-PCNSL-SG-1, before 2006: [[#Methotrexate_monotherapy_2|High-dose methotrexate]] x 6
-*G-PCNSL-SG-1, after 2006: [[#Ifosfamide_.26_Methotrexate|High-dose methotrexate & ifosfamide]] x 6
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Radiotherapy====
-*[[External_beam_radiotherapy|Whole-brain irradiation]] to 45 Gy by the following study-specific criteria:
-**Illerhaus et al. 2006: 1 Gy fractions, starting on day 90
-**G-PCNSL-SG-1: 1.5 Gy fractions
-**Abrey et al. 2000, RTOG 93-10, Shaw et al. 2007: 1.80 Gy fractions
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*Abrey et al. 2000 & RTOG 93-10: [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29_2|HiDAC]] consolidation
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #8, 50 Gy {{#subobject:b0e47a|Variant=1}}===
-{| class="wikitable" 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.2006.06.2117 Illerhaus et al. 2006]
-|1998-2003
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-''Note that the day count starts from the very beginning of treatment.''
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*[[#BCNU.2FTT.2C_then_auto_HSCT|BCNU/TT, then autologous hematopoietic stem cell transplant]], with partial response
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Radiotherapy====
-*[[External_beam_radiotherapy|Whole-brain irradiation]] to 50 Gy in 1 Gy fractions, starting on day 90
 </div></div>
 ===References===
-# Abrey LE, Yahalom J, DeAngelis LM. Treatment for primary CNS lymphoma: the next step. J Clin Oncol. 2000 Sep;18(17):3144-50. [https://doi.org/10.1200/JCO.2000.18.17.3144 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10963643 PubMed]
+#'''ToGA:''' Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [https://doi.org/10.1016/S0140-6736(10)61121-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20728210 PubMed] NCT01041404
-## '''Update:''' Gavrilovic IT, Hormigo A, Yahalom J, DeAngelis LM, Abrey LE. Long-term follow-up of high-dose methotrexate-based therapy with and without whole brain irradiation for newly diagnosed primary CNS lymphoma. J Clin Oncol. 2006 Oct 1;24(28):4570-4. [https://doi.org/10.1200/JCO.2006.06.6910 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17008697 PubMed]
+#'''HERIZON-GEA-01:''' NCT05152147
-# '''RTOG 93-10:''' DeAngelis LM, Seiferheld W, Schold SC, Fisher B, Schultz CJ; Radiation Therapy Oncology Group; SWOG. 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. [https://doi.org/10.1200/jco.2002.11.013 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12488408 PubMed]
+#'''KEYNOTE-811:''' NCT03615326
-<!-- Presented in part at the 47th Annual Meeting of the American Society of Hematology, Atlanta, GA, December 10-13, 2005. -->
+=Metastatic or locally advanced disease, subsequent lines of therapy=
-# 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. [https://doi.org/10.1200/jco.2006.06.2117 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16864853 PubMed]
+==Docetaxel monotherapy {{#subobject:4f3230|Regimen=1}}==
-## '''Update:''' Kasenda B, Schorb E, Fritsch K, Finke J, Illerhaus G. Prognosis after high-dose chemotherapy followed by autologous stem-cell transplantation as first-line treatment in primary CNS lymphoma--a long-term follow-up study. Ann Oncol. 2012 Oct;23(10):2670-5. Epub 2012 Apr 3. Erratum in: Ann Oncol. 2015 Mar;26(3):608-11. [https://doi.org/10.1093/annonc/mds059 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22473593 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; GOELAMS. 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. [https://doi.org/10.1038/sj.bmt.1705452 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16951691 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. [https://doi.org/10.1200/jco.2007.12.5062 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17947720 PubMed] NCT00594815
-## '''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. [https://doi.org/10.1200/jco.2013.50.4910 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5569679/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24101038 PubMed]
-# '''IELSG20:''' 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. 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. [https://doi.org/10.1016/S0140-6736(09)61416-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19767089 PubMed] NCT00210314
-# '''G-PCNSL-SG-1:''' 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. [https://doi.org/10.1016/S1470-2045(10)70229-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20970380 PubMed] NCT00153530
-<!-- ## '''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) [http://meetinglibrary.asco.org/content/129168-144 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. [http://www.neurology.org/content/84/12/1242.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/25716362 PubMed]
-# '''RTOG 0227:''' Glass J, Won M, Schultz CJ, Brat D, Bartlett NL, Suh JH, Werner-Wasik M, Fisher BJ, Liepman MK, Augspurger M, Bokstein F, Bovi JA, Solhjem MC, Mehta MP. Phase I and II study of induction chemotherapy with methotrexate, rituximab, and temozolomide, followed by whole-brain radiotherapy and postirradiation temozolomide for primary CNS lymphoma: NRG Oncology RTOG 0227. J Clin Oncol. 2016 May 10;34(14):1620-5. Epub 2016 Mar 28. [https://doi.org/10.1200/jco.2015.64.8634 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872318/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27022122 PubMed] NCT00068250
-# '''IELSG32:''' Ferreri AJ, Cwynarski K, Pulczynski E, Ponzoni M, Deckert M, Politi LS, Torri V, Fox CP, Rosée PL, Schorb E, Ambrosetti A, Roth A, Hemmaway C, Ferrari A, Linton KM, Rudà R, Binder M, Pukrop T, Balzarotti M, Fabbri A, Johnson P, Gørløv JS, Hess G, Panse J, Pisani F, Tucci A, Stilgenbauer S, Hertenstein B, Keller U, Krause SW, Levis A, Schmoll HJ, Cavalli F, Finke J, Reni M, Zucca E, Illerhaus G; International Extranodal Lymphoma Study Group. Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial. Lancet Haematol. 2016 May;3(5):e217-27. Epub 2016 Apr 6. [https://doi.org/10.1016/S2352-3026(16)00036-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27132696 PubMed] NCT01011920
-## '''Update:''' Ferreri AJM, Cwynarski K, Pulczynski E, Fox CP, Schorb E, La Rosée P, Binder M, Fabbri A, Torri V, Minacapelli E, Falautano M, Ilariucci F, Ambrosetti A, Roth A, Hemmaway C, Johnson P, Linton KM, Pukrop T, Sønderskov Gørløv J, Balzarotti M, Hess G, Keller U, Stilgenbauer S, Panse J, Tucci A, Orsucci L, Pisani F, Levis A, Krause SW, Schmoll HJ, Hertenstein B, Rummel M, Smith J, Pfreundschuh M, Cabras G, Angrilli F, Ponzoni M, Deckert M, Politi LS, Finke J, Reni M, Cavalli F, Zucca E, Illerhaus G; International Extranodal Lymphoma Study Group. Whole-brain radiotherapy or autologous stem-cell transplantation as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in patients with primary CNS lymphoma: results of the second randomisation of the International Extranodal Lymphoma Study Group-32 phase 2 trial. Lancet Haematol. 2017 Nov;4(11):e510-e523. Epub 2017 Oct 17. [https://doi.org/10.1016/S2352-3026(17)30174-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29054815 PubMed]
-=Relapsed or refractory, salvage therapy=
-==High-dose Cytarabine monotherapy (HiDAC) {{#subobject:c36841|Regimen=1}}==
-HiDAC: '''<u>Hi</u>'''gh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:9c7334|Variant=1}}===
+===Regimen {{#subobject:3b47ab|Variant=1}}===
-{| class="wikitable" style="width: 60%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 20%" |Study
-!style="width: 33%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! 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/S1470-2045(10)70229-1 Thiel et al. 2010 (G-PCNSL-SG-1)]
+|[https://doi.org/10.1016/S1470-2045(17)30111-0 Thuss-Patience et al. 2017 (GATSBY)]
-|2000-2009
+|2012-2013
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#1a9851" |Phase 2/3 (C)
+|[[#Trastuzumab_emtansine_monotherapy_99|T-DM1]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 8.6 vs 7.9 mo<br>(HR 0.87, 95% CI 0.66-1.15)
 |-
 |}
-<div class="toccolours" style="background-color:#cbd5e8">
+''Note: study patients could only have been treated by one other regimen and could not have been exposed to anthracyclines''
-====Preceding treatment====
+''Patients: 68% gastric, 32% GEJ''
-*Before 2006: Non-response to [[#Methotrexate_monotherapy_2|High-dose methotrexate]]
+<div class="toccolours" style="background-color:#fdcdac">
-*After 2006: Non-response to [[#Ifosfamide_.26_Methotrexate|Methotrexate & Ifosfamide]]
+====Biomarker eligibility criteria====
+*HER2-positive disease
 </div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 & 2
+*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
-'''21-day cycle for 4 cycles'''
+'''21-day cycles'''
 </div></div>
 ===References===
-# '''G-PCNSL-SG-1:''' 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. [https://doi.org/10.1016/S1470-2045(10)70229-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20970380 PubMed] NCT00153530
+#'''GATSBY:''' Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017 May;18(5):640-653. Epub 2017 Mar 23. [https://doi.org/10.1016/S1470-2045(17)30111-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28343975 PubMed] NCT01641939
-<!-- ## '''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) [http://meetinglibrary.asco.org/content/129168-144 link to abstract] -->
+==Trastuzumab deruxtecan monotherapy {{#subobject:d2616v|Regimen=1}}==
-## '''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. [http://www.neurology.org/content/84/12/1242.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/25716362 PubMed]
-==CYVE {{#subobject:a2d919|Regimen=1}}==
-CYVE: '''<u>CY</u>'''tarabine, '''<u>VE</u>'''pesid (Etoposide)
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1 {{#subobject:b4b13a|Variant=1}}===
+===Regimen {{#subobject:577cd6|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 20%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Years of enrollment
-|-
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-|[https://doi.org/10.1200/jco.2001.19.3.742 Soussain et al. 2001]
+! style="width: 20%" |Comparator
-|style="background-color:#91cf61"|Pilot, >20 pts
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/jco.2007.13.5533 Soussain et al. 2008]
+|[https://doi.org/10.1056/nejmoa2004413 Shitara et al. 2020 (DESTINY-Gastric01)]
-|style="background-color:#91cf61"|Phase 2
+|2017-2019
+| style="background-color:#1a9851" |Randomized Phase 2 (E-RT-switch-ooc)
+|Investigator's choice of:<br> 1. [[#Irinotecan_monotherapy_2|Irinotecan]]<br>2. [[#Paclitaxel_monotherapy|Paclitaxel]]
+| style="background-color:#1a9850" |Superior OS<br>Median OS: 12.5 vs 8.4 mo<br>(HR 0.59, 95% CI 0.39-0.88)
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''Note: the dose is different from the FDA-approved dose for breast cancer.''
-====Chemotherapy====
+''Patients had received a median of two prior therapies for advanced or metastatic disease (17% had received at least four prior therapies, 72% had previously received ramucirumab and 86% had received taxanes).''
-*[[Cytarabine (Ara-C)]] as follows:
+''The median time since the last administration of trastuzumab was 5.9 months in the trastuzumab deruxtecan group and 6.5 months among those in the investigator's choice group.''
-**2000 mg/m<sup>2</sup> IV over 3 hours once per day on days 2 to 5
+<div class="toccolours" style="background-color:#fdcdac">
-**50 mg/m<sup>2</sup> IV over 12 hours once per day on days 1 to 5
+====Biomarker eligibility criteria====
-*[[Etoposide (Vepesid)]] 200 mg/m<sup>2</sup> IV over 2 hours once per day on days 2 to 5
+*HER2 over-expression
-'''2 cycles'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*Responders: [[#Bu.2FTT.2FCy.2C_then_auto_HSCT_2|Bu/TT/Cy, then autologous hematopoietic stem cell transplant]]
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2 {{#subobject:921bc8|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/10.1038/sj.bmt.1705452 Colombat et al. 2006]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*Non-response to [[#MVBP|MVBP]] x 2
 </div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
+====Antibody-drug conjugate therapy====
-*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV every 12 hours on days 1 & 2
+*[[Trastuzumab deruxtecan (Enhertu)]] 6.4 mg/kg IV once on day 1
-*[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV once per day on days 1 & 2
+'''21-day cycles'''
-'''2 cycles (length not specified)'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*[[#Whole_brain_irradiation_2|Whole-brain irradiation]]
 </div></div>
 ===References===
-# Soussain C, Suzan F, Hoang-Xuan K, Cassoux N, Levy V, Azar N, Belanger C, Achour E, Ribrag V, Gerber S, Delattre JY, Leblond V. Results of intensive chemotherapy followed by hematopoietic stem-cell rescue in 22 patients with refractory or recurrent primary CNS lymphoma or intraocular lymphoma. J Clin Oncol. 2001 Feb 1;19(3):742-9. [https://doi.org/10.1200/jco.2001.19.3.742 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11157026 PubMed]
+#'''DESTINY-Gastric01:''' Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419-2430. Epub 2020 May 29. [https://doi.org/10.1056/nejmoa2004413 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32469182 PubMed] NCT03329690
-# 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; GOELAMS. 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. [https://doi.org/10.1038/sj.bmt.1705452 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16951691 PubMed]
+==Irinotecan monotherapy {{#subobject:6df2c0|Regimen=1}}==
-# Soussain C, Hoang-Xuan K, Taillandier L, Fourme E, Choquet S, Witz F, Casasnovas O, Dupriez B, Souleau B, Taksin AL, Gisselbrecht C, Jaccard A, Omuro A, Sanson M, Janvier M, Kolb B, Zini JM, Leblond V; Société Française de Greffe de Moëlle Osseuse-Thérapie Cellulaire. Intensive chemotherapy followed by hematopoietic stem-cell rescue for refractory and recurrent primary CNS and intraocular lymphoma: Société Française de Greffe de Moëlle Osseuse-Thérapie Cellulaire. J Clin Oncol. 2008 May 20;26(15):2512-8. Epub 2008 Apr 14. [https://doi.org/10.1200/jco.2007.13.5533 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18413641 PubMed]
-==Ifosfamide & Methotrexate {{#subobject:683c6d|Regimen=1}}==
-*[[Example orders for High-dose Methotrexate (MTX) & Ifosfamide in lymphoma]]
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:1c70bc|Variant=1}}===
+===Regimen {{#subobject:fa1ef9|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 20%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! 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/10.1007/s00277-008-0575-8 Fischer et al. 2008]
+|[https://doi.org/10.1056/nejmoa2004413 Shitara et al. 2020 (DESTINY-Gastric01)]
-|style="background-color:#ffffbe"|Retrospective
+|2017-2019
+| style="background-color:#1a9851" |Randomized Phase 2 (C)
+|[[#Trastuzumab_deruxtecan_monotherapy|Trastuzumab deruxtecan]]
+| style="background-color:#d73027" |Inferior OS
 |-
 |}
+<div class="toccolours" style="background-color:#fdcdac">
+====Biomarker eligibility criteria====
+*DESTINY-Gastric01: HER2 over-expression
+</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Ifosfamide (Ifex)]] 1500 to 2000 mg/m<sup>2</sup> IV over 3 hours once per day on days 3 to 5
+*[[Irinotecan (Camptosar)]] 150 mg/m<sup>2</sup> IV once on day 1
-*[[Methotrexate (MTX)]] 4000 mg/m<sup>2</sup> IV over 4 hours once on day 1
+'''14-day cycles'''
-====Supportive therapy====
-*[[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 CrCl less than 100 mL/min/1.73m<sup>2</sup> according to the following formula:
-*Dose of methotrexate = (CrCl/100) x 4000 mg/m<sup>2</sup>; the paper did not specify what method was used for calculating CrCl. Patients with CrCl less than 50 mL/min/1.73m<sup>2</sup> were excluded from the study.
-'''Up to 8 cycles''' (reference did not list timing/criteria to be used for next cycle of therapy)
 </div></div>
 ===References===
-# '''Retrospective:''' 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. [https://doi.org/10.1007/s00277-008-0575-8 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18679681 PubMed]
+#'''DESTINY-Gastric01:''' Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419-2430. Epub 2020 May 29. [https://doi.org/10.1056/nejmoa2004413 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32469182 PubMed] NCT03329690
-==Whole brain irradiation {{#subobject:49c1e3|Regimen=1}}==
+==Paclitaxel monotherapy {{#subobject:2dcad9|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1 {{#subobject:1475db|Variant=1}}===
+===Regimen variant #1, 80 mg/m<sup>2</sup> weekly {{#subobject:0e8f41|Variant=1}}===
-{| class="wikitable" style="width: 60%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 20%" |Study
-!style="width: 33%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! 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/S1470-2045(10)70229-1 Thiel et al. 2010 (G-PCNSL-SG-1)]
+|[https://doi.org/10.1016/S1470-2045(17)30111-0 Thuss-Patience et al. 2017 (GATSBY)]
-|2000-2009
+|2012-2013
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#1a9851" |Phase 2/3 (C)
+|[[#Trastuzumab_emtansine_monotherapy_99|T-DM1]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 8.6 vs 7.9 mo<br>(HR 0.87, 95% CI 0.66-1.15)
 |-
 |}
-<div class="toccolours" style="background-color:#cbd5e8">
+''GATSBY included patients with GE junction malignancy (68% gastric, 32% GE junction)''
-====Preceding treatment====
+<div class="toccolours" style="background-color:#fdcdac">
-*Before 2006: Non-response to [[#Methotrexate_monotherapy_2|high-dose MTX]] x 6
+====Biomarker eligibility criteria====
-*After 2006: Non-response to [[#Ifosfamide_.26_Methotrexate|High-dose methotrexate & ifosfamide]] x 6
+*Overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation
 </div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Radiotherapy====
+====Chemotherapy====
-*[[External_beam_radiotherapy|Whole-brain irradiation]] to 45 Gy in 1.5 Gy fractions
+*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
+'''21-day cycles'''
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2 {{#subobject:d82ebe|Variant=1}}===
+===Regimen variant #2, 80 mg/m<sup>2</sup>, 3 out of 4 weeks {{#subobject:dd21e8|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 20%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Years of enrollment
-|-
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-|[https://doi.org/10.1038/sj.bmt.1705452 Colombat et al. 2006]
+! style="width: 20%" |Comparator
-|style="background-color:#91cf61"|Phase 2
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|}
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*[[#CYVE_2|CYVE]] salvage
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Radiotherapy====
-*[[External_beam_radiotherapy|Whole-brain irradiation]] to 30 Gy in 1.8 Gy fractions plus 10 Gy boost to the tumor bed
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #3 {{#subobject:a2619f|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.2005.01.161 Nguyen et al. 2005]
+|[https://doi.org/10.1200/JCO.2013.53.6136 Satoh et al. 2014 (TyTAN)]
-|style="background-color:#91cf61"|Phase 2
+|2007-2009
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Lapatinib_.26_Paclitaxel_99|Lapatinib & Paclitaxel]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 8.9 vs 11 mo<br>(HR 1.19, 95% CI 0.90-1.56)
 |-
-|}
+|[https://doi.org/10.1056/nejmoa2004413 Shitara et al. 2020 (DESTINY-Gastric01)]
-''The authors do not clearly describe a pre-determined dosing protocol but report that the most common fraction size was 1.5 Gy.''
+|2017-2019
-====Radiotherapy====
+| style="background-color:#1a9851" |Randomized Phase 2 (C)
-*Median dose:
+|[[#Trastuzumab_deruxtecan_monotherapy|Trastuzumab deruxtecan]]
-**Patients not receiving a boost: 36 Gy (range 28 to 45 Gy)
+| style="background-color:#d73027" |Inferior OS
-**Patients receiving a boost: 36 Gy (range 19.6 to 40 Gy) + 10 Gy (range 10 to 21.6 Gy)
-</div></div>
-===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. [https://doi.org/10.1200/jco.2005.01.161 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15735126 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; GOELAMS. 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. [https://doi.org/10.1038/sj.bmt.1705452 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16951691 PubMed]
-# '''G-PCNSL-SG-1:''' 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. [https://doi.org/10.1016/S1470-2045(10)70229-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20970380 PubMed] NCT00153530
-<!-- ## '''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) [http://meetinglibrary.asco.org/content/129168-144 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. [http://www.neurology.org/content/84/12/1242.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/25716362 PubMed]
-=Consolidation after salvage therapy=
-==Bu/TT/Cy, then auto HSCT {{#subobject:3f8412|Regimen=1}}==
-Bu/TT/Cy: '''<u>Bu</u>'''sulfan, '''<u>T</u>'''hio'''<u>T</u>'''epa, '''<u>Cy</u>'''clophosphamide
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:ab67a7|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.2001.19.3.742 Soussain et al. 2001]
-|style="background-color:#91cf61"|Pilot, >20 pts
-|-
-|[https://doi.org/10.1200/jco.2007.13.5533 Soussain et al. 2008]
-|style="background-color:#91cf61"|Phase 2
 |-
 |}
-<div class="toccolours" style="background-color:#cbd5e8">
+<div class="toccolours" style="background-color:#fdcdac">
-====Preceding treatment====
+====Biomarker eligibility criteria====
-*[[#CYVE_2|CYVE]] salvage x 2
+*HER2-positive disease
 </div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Busulfan (Myleran)]] by the following age-based criteria:
+*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15
-**Up to 60 years old: 10 mg/kg PO or 8 mg/kg IV once per day on days -6, -5, and -4
+'''28-day cycles'''
-**60 and older: 6 mg/kg PO or 4.8 mg/kg IV once per day on days -6, -5, and -4
-*[[Thiotepa (Thioplex)]] 250 mg/m<sup>2</sup> IV once per day on days -9, -8, and -7
-*[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV once per day on days -3 & -2
-====Supportive therapy====
-*[[Clonazepam (Klonopin)]] 2 mg/day IV from the first day of [[Busulfan (Myleran)]] until completion of [[Busulfan (Myleran)]]
-'''Stem cell re-infusion occurs on day 0'''
 </div></div>
 ===References===
-# Soussain C, Suzan F, Hoang-Xuan K, Cassoux N, Levy V, Azar N, Belanger C, Achour E, Ribrag V, Gerber S, Delattre JY, Leblond V. Results of intensive chemotherapy followed by hematopoietic stem-cell rescue in 22 patients with refractory or recurrent primary CNS lymphoma or intraocular lymphoma. J Clin Oncol. 2001 Feb 1;19(3):742-9. [https://doi.org/10.1200/jco.2001.19.3.742 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11157026 PubMed]
+#'''TyTAN:''' Satoh T, Xu RH, Chung HC, Sun GP, Doi T, Xu JM, Tsuji A, Omuro Y, Li J, Wang JW, Miwa H, Qin SK, Chung IJ, Yeh KH, Feng JF, Mukaiyama A, Kobayashi M, Ohtsu A, Bang YJ. Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: TyTAN--a randomized, phase III study. J Clin Oncol. 2014 Jul 1;32(19):2039-49. Epub 2014 May 27. [https://doi.org/10.1200/JCO.2013.53.6136 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24868024 PubMed] NCT00486954
-# Soussain C, Hoang-Xuan K, Taillandier L, Fourme E, Choquet S, Witz F, Casasnovas O, Dupriez B, Souleau B, Taksin AL, Gisselbrecht C, Jaccard A, Omuro A, Sanson M, Janvier M, Kolb B, Zini JM, Leblond V; Société Française de Greffe de Moëlle Osseuse-Thérapie Cellulaire. Intensive chemotherapy followed by hematopoietic stem-cell rescue for refractory and recurrent primary CNS and intraocular lymphoma: Société Française de Greffe de Moëlle Osseuse-Thérapie Cellulaire. J Clin Oncol. 2008 May 20;26(15):2512-8. Epub 2008 Apr 14. [https://doi.org/10.1200/jco.2007.13.5533 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18413641 PubMed]
+#'''GATSBY:''' Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017 May;18(5):640-653. Epub 2017 Mar 23. [https://doi.org/10.1016/S1470-2045(17)30111-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28343975 PubMed] NCT01641939
-=Relapsed or refractory, subsequent lines of therapy=
+#'''DESTINY-Gastric01:''' Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419-2430. Epub 2020 May 29. [https://doi.org/10.1056/nejmoa2004413 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32469182 PubMed] NCT03329690
-==Rituximab monotherapy {{#subobject:b1f8c5|Regimen=1}}==
+==Paclitaxel & Ramucirumab {{#subobject:fdd93f|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:3e2c19|Variant=1}}===
+===Regimen {{#subobject:f66446|Variant=1}}===
-{| class="wikitable sortable" style="width: 60%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 20%" |Study
-!style="width: 33%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! 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/PMC3059144/ Batchelor et al. 2011 (NABTT-2201)]
+|Awaiting publication (DESTINY-Gastric04)
-|2004-NR
+|2021-ongoing
-|style="background-color:#ffffbe"|Pilot, <20 pts
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Trastuzumab_deruxtecan_monotherapy|Trastuzumab deruxtecan]]
+| style="background-color:#d3d3d3" |In progress
 |-
 |}
+''Note: Dosing information is from CT.gov.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
-*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
+*[[Ramucirumab (Cyramza)]] 8 mg/kg IV once per day on days 1 & 15
-'''28-day cycle for up to 2 cycles'''
-</div></div>
-===References===
-# '''NABTT-2201:''' Batchelor TT, Grossman SA, Mikkelsen T, Ye for, Desideri S, Lesser GJ. Rituximab monotherapy for patients with recurrent primary CNS lymphoma. Neurology. 2011 Mar 8;76(10):929-30. [http://www.neurology.org/content/76/10/929.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3059144/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21383331 PubMed] NCT00072449
-==Temozolomide monotherapy {{#subobject:be70fc|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:23777b|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360092/ Reni et al. 2007]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Temozolomide (Temodar)]] 150 mg/m<sup>2</sup> PO once per day on days 1 to 5
+*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 '''28-day cycles'''
 </div></div>
 ===References===
-# Reni M, Zaja F, Mason W, Perry J, Mazza E, Spina M, Bordonaro R, Ilariucci F, Faedi M, Corazzelli G, Manno P, Franceschi E, Pace A, Candela M, Abbadessa A, Stelitano C, Latte G, Ferreri AJ. Temozolomide as salvage treatment in primary brain lymphomas. Br J Cancer. 2007 Mar 26;96(6):864-7. Epub 2007 Feb 27. [https://doi.org/10.1038/sj.bjc.6603660 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360092/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/17325700 PubMed]
+#'''DESTINY-Gastric04:''' NCT04704934
-==Temsirolimus monotherapy {{#subobject:021ac0|Regimen=1}}==
+[[Category:Gastric cancer regimens]]
-<div class="toccolours" style="background-color:#eeeeee">
+[[Category:Biomarker-specific pages]]
-===Regimen {{#subobject:0ad4c0|Variant=1}}===
+[[Category:Gastroesophageal cancers]]
-{| 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.2015.64.9897 Korfel et al. 2016 (TemPCNSL)]
-|style="background-color:#91cf61"|Phase 2
-|-
-|}
-''This is the dose used in stage 2 of this two-stage protocol.''
-====Targeted therapy====
-*[[Temsirolimus (Torisel)]] 75 mg IV once per day on days 1, 8, 15, 22
-'''28-day cycles'''
-</div></div>
-===References===
-# '''TemPCNSL:''' Korfel A, Schlegel U, Herrlinger U, Dreyling M, Schmidt C, von Baumgarten L, Pezzutto A, Grobosch T, Kebir S, Thiel E, Martus P, Kiewe P. Phase II trial of temsirolimus for relapsed/refractory primary CNS lymphoma. J Clin Oncol. 2016 May 20;34(15):1757-63. Epub 2016 Mar 14. [https://doi.org/10.1200/jco.2015.64.9897 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26976424 PubMed] NCT00942747
-==Topotecan monotherapy {{#subobject:f51103|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:26ef01|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/10.1093/annonc/mdl070 Fischer et al. 2006]
-|style="background-color:#91cf61"|Phase 2
-|-
-|[http://link.springer.com/article/10.1007/s11060-007-9464-6 Voloschin et al. 2008]
-|style="background-color:#ffffbe"|Phase 2, <20 pts
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Topotecan (Hycamtin)]] 1.5 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5
-====Supportive therapy====
-*Voloschin et al. 2008: [[Ondansetron (Zofran)]] (dose/route not specified) prior to [[Topotecan (Hycamtin)]]
-'''21-day cycle for 6 to 10 cycles'''
-</div></div>
-===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. [https://doi.org/10.1093/annonc/mdl070 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16603598 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. [http://link.springer.com/article/10.1007/s11060-007-9464-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17896078 PubMed]
-=Prognosis=
-==IELSG Prognostic Scoring System (2003)==
-# Ferreri AJ, Blay JY, Reni M, Pasini F, Spina M, Ambrosetti A, Calderoni A, Rossi A, Vavassori V, Conconi A, Devizzi L, Berger F, Ponzoni M, Borisch B, Tinguely M, Cerati M, Milani M, Orvieto E, Sanchez J, Chevreau C, Dell'Oro S, Zucca E, Cavalli F. Prognostic scoring system for primary CNS lymphomas: the International Extranodal Lymphoma Study Group experience. J Clin Oncol. 2003 Jan 15;21(2):266-72. [https://doi.org/10.1200/jco.2003.09.139 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12525518 PubMed]
-[[Category:CNS lymphoma regimens]]
-[[Category:Disease-specific pages]]
-[[Category:CNS cancers]]

Difference between revisions of "Staging page"

Revision as of 12:12, 15 October 2022

Guidelines

CAP/ASCP/ASCO

Metastatic or locally advanced disease, first-line

Capecitabine & Cisplatin (CX)

Regimen

Biomarker eligibility criteria

Chemotherapy

References

Capecitabine & Cisplatin (CX) & Trastuzumab

Regimen variant #1, 80/1600

Biomarker eligibility criteria

Chemotherapy

Targeted therapy

Subsequent treatment

Regimen variant #2, 80/2000

Biomarker eligibility criteria

Chemotherapy

Targeted therapy

References

CapeOx

Regimen

Biomarker eligibility criteria

Chemotherapy

References

CapeOx, Pembrolizumab, Trastuzumab

Regimen

Biomarker eligibility criteria

Chemotherapy

Immunotherapy

Targeted therapy

References

CapeOx & Trastuzumab

Regimen

Biomarker eligibility criteria

Chemotherapy

Targeted therapy

References

Cisplatin & Fluorouracil (CF)

Regimen

Biomarker eligibility criteria

Chemotherapy

References

Cisplatin & Fluorouracil (CF) & Trastuzumab

Regimen

Biomarker eligibility criteria

Chemotherapy

Targeted therapy

References

Metastatic or locally advanced disease, subsequent lines of therapy

Docetaxel monotherapy

Regimen

Biomarker eligibility criteria

Chemotherapy

References

Trastuzumab deruxtecan monotherapy

Regimen

Biomarker eligibility criteria

Antibody-drug conjugate therapy

References

Irinotecan monotherapy

Regimen

Biomarker eligibility criteria

Chemotherapy

References

Paclitaxel monotherapy

Regimen variant #1, 80 mg/m2 weekly

Biomarker eligibility criteria

Chemotherapy

Regimen variant #2, 80 mg/m2, 3 out of 4 weeks

Biomarker eligibility criteria

Chemotherapy

References

Paclitaxel & Ramucirumab

Regimen

Targeted therapy

Chemotherapy

References

Navigation menu

Regimen variant #1, 80 mg/m² weekly

Regimen variant #2, 80 mg/m², 3 out of 4 weeks