FCM (chemotherapy)

FCM, or FMC in the context of chemotherapy is an acronym for a chemotherapy regimen that is used in the treatment of indolent B cell non-Hodgkin's lymphomas. In combination with Rituximab, this regimen is called R-FCM or R-FMC, or FCM-R, FMC-R.

The [R]-FCM regimen contains

1. Rituximab - anti-CD20 monoclonal antibody that can kill both normal and malignant CD20-bearing B cells;
2. Fludarabine - an antimetabolite;
3. Cyclophosphamide - an alkylating antineoplastic agent from the oxazafosforine group;
4. Mitoxantrone - a synthetic anthracycline analogue (anthraquinone) that can intercalate DNA, thereby preventing cell division.^[1]

Clinical use

The addition of monoclonal antibodies like rituximab to chemotherapy regimens has increased treatment outcomes for patients with indolent B cell non-Hodgkin's lymphomas, including chronic lymphocytic leukemia.^[2] R-FCM regimens were recommended prior to the discovery of targeted therapies, such as Bruton tyrosine kinase inhibitors and Bcl-2 inhibitors, but trials have shown the superiority of targeted therapies in terms of survival and side effect profiles.^[3][4] R-FCM can be considered in resource-limited settings without access to targeted therapies. R-FCM should not be considered in patients with a 17p deletion, a TP53 mutations, and in patients with unmutated immunoglobulin heavy chain variable (IGHV), as R-FCM is less effective than targeted therapies.^[5]

Dosing regimen

The recommended dosing schedule for R-FCM is based on patient weight and general fitness. Each cycle lasts 28 days for a maximum of 6 cycles.^[6]

Drug	Dose	Mode	Days
Rituximab	375 mg/m2	IV infusion[7]	Day 0
Fludarabine	25 mg/m2	IV infusion over 30 min[7]	Days 1-3
Cyclophosphamide	250 mg/m2	IV infusion over 4 hours[7]	Days 1-3
Mitoxantrone	8 mg/m2	IV infusion over 30 min[8]	Day 1

References

1. Forstpointner, R.; Dreyling, M.; Repp, R.; Hermann, S.; Hänel, A.; Metzner, B.; Pott, C.; Hartmann, F.; Rothmann, F.; Rohrberg, R.; Böck, H. P.; Wandt, H.; Unterhalt, M.; Hiddemann, W.; German Low-Grade Lymphoma Study Group (2004). "The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group". Blood. 104 (10): 3064–3071. doi:10.1182/blood-2004-04-1323. PMID 15284112. Retrieved 2023-07-11.
2. Bosch, Francesc; Abrisqueta, Pau; Villamor, Neus; Terol, María José; González-Barca, Eva; Ferra, Christelle; González Diaz, Marcos; Abella, Eugenia; Delgado, Julio; Carbonell, Félix; García Marco, José Antonio; Escoda, Lourdes; Ferrer, Secundino; Monzó, Encarnación; González, Yolanda (2009-09-20). "Rituximab, fludarabine, cyclophosphamide, and mitoxantrone: a new, highly active chemoimmunotherapy regimen for chronic lymphocytic leukemia". Journal of Clinical Oncology. 27 (27): 4578–4584. doi:10.1200/JCO.2009.22.0442. ISSN 1527-7755. PMID 19704063.
3. Woyach, Jennifer A.; Ruppert, Amy S.; Heerema, Nyla A.; Zhao, Weiqiang; Booth, Allison M.; Ding, Wei; Bartlett, Nancy L.; Brander, Danielle M.; Barr, Paul M.; Rogers, Kerry A.; Parikh, Sameer A.; Coutre, Steven; Hurria, Arti; Brown, Jennifer R.; Lozanski, Gerard (2018-12-27). "Ibrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL". New England Journal of Medicine. 379 (26): 2517–2528. doi:10.1056/NEJMoa1812836. ISSN 0028-4793. PMC 6325637. PMID 30501481.
4. Shanafelt, Tait D.; Wang, Xin V.; Kay, Neil E.; Hanson, Curtis A.; O’Brien, Susan; Barrientos, Jacqueline; Jelinek, Diane F.; Braggio, Esteban; Leis, Jose F.; Zhang, Cong C.; Coutre, Steven E.; Barr, Paul M.; Cashen, Amanda F.; Mato, Anthony R.; Singh, Avina K. (2019-08-01). "Ibrutinib–Rituximab or Chemoimmunotherapy for Chronic Lymphocytic Leukemia". New England Journal of Medicine. 381 (5): 432–443. doi:10.1056/NEJMoa1817073. ISSN 0028-4793. PMC 6908306. PMID 31365801.
5. Cramer, Paula; Langerbeins, Petra; Eichhorst, Barbara; Hallek, Michael (2015-09-02). "Advances in first-line treatment of chronic lymphocytic leukemia: current recommendations on management and first-line treatment by the German CLL Study Group (GCLLSG)". European Journal of Haematology. 96 (1): 9–18. doi:10.1111/ejh.12678. PMID 26332019. S2CID 25952767.
6. Szász, Róbert; Telek, Béla; Illés, Árpád (2021-04-27). "Fludarabine-Cyclophosphamide-Rituximab Treatment in Chronic Lymphocytic Leukemia, Focusing on Long Term Cytopenias Before and After the Era of Targeted Therapies". Pathology & Oncology Research. 27: 1609742. doi:10.3389/pore.2021.1609742. ISSN 1219-4956. PMC 8262186. PMID 34257611.
7. Tam, Constantine S.; O'Brien, Susan; Wierda, William; Kantarjian, Hagop; Wen, Sijin; Do, Kim-Anh; Thomas, Deborah A.; Cortes, Jorge; Lerner, Susan; Keating, Michael J. (2008-08-15). "Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia". Blood. 112 (4): 975–980. doi:10.1182/blood-2008-02-140582. ISSN 0006-4971. PMC 3952498. PMID 18411418.
8. Bosch, Francesc; Ferrer, Anna; López-Guillermo, Armando; Giné, Eva; Bellosillo, Beatriz; Villamor, Neus; Colomer, Dolors; Cobo, Francesc; Perales, María; Esteve, Jordi; Altés, Albert; Besalduch, Joan; Ribera, Josep M.; Montserrat, Emili; GELCAB (Grup per l'Estudi dels Limfomes a Catalunya i Balears) (2002-12-11). "Fludarabine, cyclophosphamide and mitoxantrone in the treatment of resistant or relapsed chronic lymphocytic leukaemia". British Journal of Haematology. 119 (4): 976–984. doi:10.1046/j.1365-2141.2002.03959.x. ISSN 0007-1048. PMID 12472576. S2CID 9622709.