Erdheim-Chester disease
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3 regimens on this page
4 variants on this page
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Erdheim-Chester disease (ECD)
Sirolimus & Prednisone
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Regimen
| Study | Evidence |
| Gianfreda et al. 2015 | Pilot, <20 pts in this arm |
Chemotherapy
- Sirolimus (Rapamune) 2 mg PO once per day, titrated to achieve a blood level of 8 to 12 ng/mL
- Prednisone (Sterapred) as follows:
- Month 1: 0.75 mg/kg/day PO
- Month 2: 0.5 mg/k/day PO
- Months 3 & 4: 0.25 mg/kg/day PO
- Months 5 & 6: 0.125 mg/kg/day PO
- Month 7 onwards: tapered to a dose of 2.5 to 5 mg PO once per day
Given for up to 2 years for responders and stable disease, with optional extension beyond 2 years
References
- Gianfreda D, Nicastro M, Galetti M, Alberici F, Corradi D, Becchi G, Baldari G, De Filippo M, Ferretti S, Moroni G, Foti R, Di Gangi M, Jeannin G, Saffroy R, Emile JF, Buzio C, Vaglio A. Sirolimus plus prednisone for Erdheim-Chester disease: an open-label trial. Blood. 2015 Sep 3;126(10):1163-71. Epub 2015 Jun 3. link to original article contains verified protocol PubMed
Vemurafenib (Zelboraf)
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Regimen #1
| Study | Evidence |
| Hyman et al. 2015 | Phase II, <20 pts in this arm |
This was part of a basket trial, all patients had BRAF V600E mutations.
Chemotherapy
- Vemurafenib (Zelboraf) 960 mg PO BID
Duration of treatment not specified
Regimen #2
| Study | Evidence |
| Haroche et al. 2014 | Pilot, <20 pts |
Patients enrolled all had BRAF V600E mutation. This is the dose after de-escalation after the first four patients had excess adverse events.
Chemotherapy
- Vemurafenib (Zelboraf) 480 mg PO BID
Given until progression of disease or unacceptable toxicity
References
- Haroche J, Cohen-Aubart F, Emile JF, Maksud P, Drier A, Tolédano D, Barete S, Charlotte F, Cluzel P, Donadieu J, Benameur N, Grenier PA, Besnard S, Ory JP, Lifermann F, Idbaih A, Granel B, Graffin B, Hervier B, Arnaud L, Amoura Z. Reproducible and Sustained Efficacy of Targeted Therapy With Vemurafenib in Patients With BRAFV600E-Mutated Erdheim-Chester Disease. J Clin Oncol. 2015 Feb 10;33(5):411-8. Epub 2014 Nov 24. link to original article contains verified protocol PubMed
- Hyman DM, Puzanov I, Subbiah V, Faris JE, Chau I, Blay JY, Wolf J, Raje NS, Diamond EL, Hollebecque A, Gervais R, Elez-Fernandez ME, Italiano A, Hofheinz RD, Hidalgo M, Chan E, Schuler M, Lasserre SF, Makrutzki M, Sirzen F, Veronese ML, Tabernero J, Baselga J. Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. N Engl J Med. 2015 Aug 20;373(8):726-736. link to original article contains protocol PubMed
Langerhans cell histiocytosis (LCH)
Cladribine (Leustatin)
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Regimen
| Study | Evidence |
| Weitzman et al. 2009 (LCH-S-98) | Phase II |
To be completed
Chemotherapy
References
- Weitzman S, Braier J, Donadieu J, Egeler RM, Grois N, Ladisch S, Pötschger U, Webb D, Whitlock J, Arceci RJ. 2'-Chlorodeoxyadenosine (2-CdA) as salvage therapy for Langerhans cell histiocytosis (LCH). results of the LCH-S-98 protocol of the Histiocyte Society. Pediatr Blood Cancer. 2009 Dec 15;53(7):1271-6. link to original article PubMed
Cladribine & Cytarabine
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Regimen
| Study | Evidence |
| Donadieu et al. 2015 | Phase II |
Chemotherapy, induction
- Cladribine (Leustatin) 9 mg/m2 IV over 2 hours once per day on days 2 to 6, should not be administered simultaneously with cytarabine
- Children weighing less than 10 kg received a dose of 0.3 mg/kg/day
- Cytarabine (Cytosar) 500 mg/m2 IV over 2 hours twice per day on days 1 to 5, should not be administered simultaneously with cladribine
5-week cycle for 2 or more cycles
Patients with a "good response" proceeded to consolidation therapy:
Chemotherapy, consolidation
- Cladribine (Leustatin) 5 mg/m2 IV once per day on days 1 to 3
21-day cycle for 2 cycles, followed by:
Chemotherapy, maintenance
- Vinblastine (Velban) 6 mg/m2 IV once every 2 weeks for 6 months
- Prednisolone (Millipred) 40 mg/m2 PO once per day on days 1 to 5 of every 2nd week for 6 months
- Mercaptopurine (Purinethol) 50 mg/m2 PO once per day for 18 months
- Methotrexate (MTX) 20 mg/m2 PO once per week for 18 months
Total of 18 months of maintenance
References
- Donadieu J, Bernard F, van Noesel M, Barkaoui M, Bardet O, Mura R, Arico M, Piguet C, Gandemer V, Armari Alla C, Clausen N, Jeziorski E, Lambilliote A, Weitzman S, Henter JI, Van Den Bos C; Salvage Group of the Histiocyte Society. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study. Blood. 2015 Sep 17;126(12):1415-23. Epub 2015 Jul 20. link to original article contains verified protocol PubMed
Etoposide & Prednisone
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Regimen
| Study | Evidence | Comparator | Efficacy |
| Gadner et al. 2001 (LCH-I) | Phase III | Vinblastine & Prednisone | Seems not superior |
To be completed
Chemotherapy
References
- Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Pötschger U, Pritchard J, Ladisch S; Histiocyte Society. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr. 2001 May;138(5):728-34. Erratum in: J Pediatr 2001 Jul;139(1):170. link to original article PubMed
Etoposide, Vinblastine, Prednisone
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Regimen
| Study | Evidence | Comparator | Efficacy |
| Gadner et al. 2007 (LCH-II) | Phase III | Vinblastine & Prednisone | Seems not superior |
Total duration of therapy is 24 weeks.
Chemotherapy, initial
- Etoposide (Vepesid) 150 mg/m2 IV over 1 hour once per week
- Vinblastine (Velban) 6 mg/m2 IV bolus once per week
- Prednisone (Sterapred) 40 mg/m2/day split TID for 4 weeks, then tapering off over 2 weeks
6-week course, followed by:
Chemotherapy, continuation
- Etoposide (Vepesid) 150 mg/m2 IV over 1 hour once on day 1
- Vinblastine (Velban) 6 mg/m2 IV bolus once on day 1
- Prednisone (Sterapred) 40 mg/m2/day split TID on days 1 to 5
3-week cycle for 6 cycles
References
- Gadner H, Grois N, Pötschger U, Minkov M, Aricò M, Braier J, Broadbent V, Donadieu J, Henter JI, McCarter R, Ladisch S; Histiocyte Society. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008 Mar 1;111(5):2556-62. Epub 2007 Dec 18. link to original article contains verified protocol PubMed
Methotrexate, Vinblastine, Prednisone
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Regimen
| Study | Evidence | Comparator | Efficacy |
| Gadner et al. 2013 (LCH-III) | Phase III | Vinblastine & Prednisone | Seems not superior |
To be completed
Chemotherapy
References
- Gadner H, Minkov M, Grois N, Pötschger U, Thiem E, Aricò M, Astigarraga I, Braier J, Donadieu J, Henter JI, Janka-Schaub G, McClain KL, Weitzman S, Windebank K, Ladisch S; Histiocyte Society. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013 Jun 20;121(25):5006-14. Epub 2013 Apr 15. link to original article PubMed
Vemurafenib (Zelboraf)
| back to top |
Regimen
| Study | Evidence |
| Hyman et al. 2015 | Phase II, <20 pts in this arm |
This was part of a basket trial, all patients had BRAF V600E mutations.
Chemotherapy
- Vemurafenib (Zelboraf) 960 mg PO BID
Duration of treatment not specified
References
- Hyman DM, Puzanov I, Subbiah V, Faris JE, Chau I, Blay JY, Wolf J, Raje NS, Diamond EL, Hollebecque A, Gervais R, Elez-Fernandez ME, Italiano A, Hofheinz RD, Hidalgo M, Chan E, Schuler M, Lasserre SF, Makrutzki M, Sirzen F, Veronese ML, Tabernero J, Baselga J. Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. N Engl J Med. 2015 Aug 20;373(8):726-736. link to original article contains protocol PubMed
Vinblastine & Prednisone
| back to top |
Regimen
| Study | Evidence | Comparator | Efficacy |
| Gadner et al. 2001 (LCH-I) | Phase III | Etoposide & Prednisone | Seems not superior |
| Gadner et al. 2007 (LCH-II) | Phase III | Etoposide, Vinblastine, Prednisone | Seems not superior |
| Gadner et al. 2013 (LCH-III) | Phase III | Methotrexate, Vinblastine, Prednisone | Seems not superior |
Total duration of therapy is 24 weeks, in LCH-II.
Chemotherapy, initial
- Vinblastine (Velban) 6 mg/m2 IV bolus once per week
- Prednisone (Sterapred) 40 mg/m2/day split TID for 4 weeks, then tapering off over 2 weeks
6-week course, followed by:
Chemotherapy, continuation
- Vinblastine (Velban) 6 mg/m2 IV bolus once on day 1
- Prednisone (Sterapred) 40 mg/m2/day split TID on days 1 to 5
3-week cycle for 6 cycles
References
- Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Pötschger U, Pritchard J, Ladisch S; Histiocyte Society. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr. 2001 May;138(5):728-34. Erratum in: J Pediatr 2001 Jul;139(1):170. link to original article PubMed
- Gadner H, Grois N, Pötschger U, Minkov M, Aricò M, Braier J, Broadbent V, Donadieu J, Henter JI, McCarter R, Ladisch S; Histiocyte Society. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008 Mar 1;111(5):2556-62. Epub 2007 Dec 18. link to original article contains verified protocol PubMed
- Gadner H, Minkov M, Grois N, Pötschger U, Thiem E, Aricò M, Astigarraga I, Braier J, Donadieu J, Henter JI, Janka-Schaub G, McClain KL, Weitzman S, Windebank K, Ladisch S; Histiocyte Society. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013 Jun 20;121(25):5006-14. Epub 2013 Apr 15. link to original article PubMed