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Systemic Anti-Cancer Therapy Regimen Library

LEU CLL - FCR [fludarabine, CYCLOPHOSPHamide and RITUximab] [oral] [5 day]

Treatment Overview

Usually 6 cycles, depending on response and toxicity fewer than 6 cycles may be given.


This regimen contains a medicine where one or more biosimilars may exist. Any biosimilars used have been reviewed by the regulator (Medsafe) and relevant specialists were consulted nationally. Where regulators, in consultation with relevant specialists, have agreed that there are no clinically significant differences in either safety or effectiveness between a biosimilar and originator product, these drugs may be used interchangeably.

Cycle 1 - 28 days

Cycle length:
28

RITUximab, first dose:

Consider withholding routine anti-hypertensives for 12 hours prior to first RITUximab dose.

In patients with lymphocytes 25 x109/L or higher, consider additional premedication with montelukast 10 mg orally and famotidine 20 mg orally both ONE hour prior to RITUximab, and/or consider splitting RITUximab dose over two days (100mg on day 1, remainder of the dose on day 2).

Cycles 2 to 6 - 28 days

Cycle length:
28

RITUximab: Consider administering corticosteroid premedication before RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.

Cycle details

Cycle 1 - 28 days

Medication Dose Route Days Max Duration
paracetamol 1000 mg flat dosing oral administration 1
loratadine * 10 mg oral administration 1
dexamethasone * 12 mg flat dosing intravenous 1 15 minutes
RITUximab 375 mg/m² intravenous 1 6 hours
fludarabine * 24 mg/m² Once daily oral administration 1 to 5
CYCLOPHOSPHamide 150 mg/m² Once daily oral administration 1 to 5
pegFILGRASTIM 6 mg subcutaneous injection 6

RITUximab, first dose:

Consider withholding routine anti-hypertensives for 12 hours prior to first RITUximab dose.

In patients with lymphocytes 25 x109/L or higher, consider additional premedication with montelukast 10 mg orally and famotidine 20 mg orally both ONE hour prior to RITUximab, and/or consider splitting RITUximab dose over two days (100mg on day 1, remainder of the dose on day 2).

Cycles 2 to 6 - 28 days

Medication Dose Route Days Max Duration
paracetamol 1000 mg flat dosing oral administration 1
loratadine * 10 mg oral administration 1
RITUximab 500 mg/m² intravenous 1 6 hours
fludarabine * 24 mg/m² Once daily oral administration 1 to 5
CYCLOPHOSPHamide 150 mg/m² Once daily oral administration 1 to 5
pegFILGRASTIM 6 mg subcutaneous injection 6

RITUximab: Consider administering corticosteroid premedication before RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.

Full details

Cycle 1 - 28 days

Day: 1

Medication Dose Route Max duration Details
paracetamol 1000 mg flat dosing oral administration
Instructions:

30 to 60 minutes prior to RITUximab.

loratadine * 10 mg oral administration
Instructions:

30 to 60 minutes prior to RITUximab.

dexamethasone * 12 mg flat dosing intravenous 15 minutes
Instructions:

30 to 60 minutes prior to RITUximab, or as per institutional practice.

RITUximab 375 mg/m² intravenous 6 hours
Instructions:

Start at 50 mg/hour. If tolerated, rate can be increased by 50 mg/hour every 30 minutes to a maximum rate of 400 mg/hour.

Consider withholding routine anti-hypertensives for 12 hours prior to RITUximab.

In patients with lymphocytes 25 x109/L or higher, consider additional premedication with montelukast 10 mg and famotidine 20 mg both orally ONE hour prior to RITUximab, and/or splitting RITUximab dose over two days (100mg on day 1, remainder of the dose on day 2).

fludarabine * 24 mg/m² Once daily oral administration
Instructions:

Swallow tablets whole with a glass of water, do not crush, chew or break.

Round dose to closest multiple of 10 mg tablets.

CYCLOPHOSPHamide 150 mg/m² Once daily oral administration
Instructions:

Take each dose with food and a large glass of water, preferably in the morning.

Round dose to closest multiple of 50 mg tablets.

Day: 2

Medication Dose Route Max duration Details
fludarabine * 24 mg/m² Once daily oral administration
Instructions:

Swallow tablets whole with a glass of water, do not crush, chew or break.

Round dose to closest multiple of 10 mg tablets.

CYCLOPHOSPHamide 150 mg/m² Once daily oral administration
Instructions:

Take each dose with food and a large glass of water, preferably in the morning.

Round dose to closest multiple of 50 mg tablets.

Day: 3

Medication Dose Route Max duration Details
fludarabine * 24 mg/m² Once daily oral administration
Instructions:

Swallow tablets whole with a glass of water, do not crush, chew or break.

Round dose to closest multiple of 10 mg tablets.

CYCLOPHOSPHamide 150 mg/m² Once daily oral administration
Instructions:

Take each dose with food and a large glass of water, preferably in the morning.

Round dose to closest multiple of 50 mg tablets.

Day: 4

Medication Dose Route Max duration Details
fludarabine * 24 mg/m² Once daily oral administration
Instructions:

Swallow tablets whole with a glass of water, do not crush, chew or break.

Round dose to closest multiple of 10 mg tablets.

CYCLOPHOSPHamide 150 mg/m² Once daily oral administration
Instructions:

Take each dose with food and a large glass of water, preferably in the morning.

Round dose to closest multiple of 50 mg tablets.

Day: 5

Medication Dose Route Max duration Details
fludarabine * 24 mg/m² Once daily oral administration
Instructions:

Swallow tablets whole with a glass of water, do not crush, chew or break.

Round dose to closest multiple of 10 mg tablets.

CYCLOPHOSPHamide 150 mg/m² Once daily oral administration
Instructions:

Take each dose with food and a large glass of water, preferably in the morning.

Round dose to closest multiple of 50 mg tablets.

Day: 6

Medication Dose Route Max duration Details
pegFILGRASTIM 6 mg subcutaneous injection

Cycles 2 to 6 - 28 days

Day: 1

Medication Dose Route Max duration Details
paracetamol 1000 mg flat dosing oral administration
Instructions:

30 to 60 minutes prior to RITUximab.

loratadine * 10 mg oral administration
Instructions:

30 to 60 minutes prior to RITUximab.

RITUximab 500 mg/m² intravenous 6 hours
Instructions:

Start at 100 mg/hour. If tolerated, rate can be increased by 100 mg/hour every 30 minutes to a maximum rate of 400 mg/hour or as per institutional practice.

Consider administering corticosteroid premedication before RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.

fludarabine * 24 mg/m² Once daily oral administration
Instructions:

Swallow tablets whole with a glass of water, do not crush, chew or break.

Round dose to closest multiple of 10 mg tablets.

CYCLOPHOSPHamide 150 mg/m² Once daily oral administration
Instructions:

Take each dose with food and a large glass of water, preferably in the morning.

Round dose to closest multiple of 50 mg tablets.

Day: 2

Medication Dose Route Max duration Details
fludarabine * 24 mg/m² Once daily oral administration
Instructions:

Swallow tablets whole with a glass of water, do not crush, chew or break.

Round dose to closest multiple of 10 mg tablets.

CYCLOPHOSPHamide 150 mg/m² Once daily oral administration
Instructions:

Take each dose with food and a large glass of water, preferably in the morning.

Round dose to closest multiple of 50 mg tablets.

Day: 3

Medication Dose Route Max duration Details
fludarabine * 24 mg/m² Once daily oral administration
Instructions:

Swallow tablets whole with a glass of water, do not crush, chew or break.

Round dose to closest multiple of 10 mg tablets.

CYCLOPHOSPHamide 150 mg/m² Once daily oral administration
Instructions:

Take each dose with food and a large glass of water, preferably in the morning.

Round dose to closest multiple of 50 mg tablets.

Day: 4

Medication Dose Route Max duration Details
fludarabine * 24 mg/m² Once daily oral administration
Instructions:

Swallow tablets whole with a glass of water, do not crush, chew or break.

Round dose to closest multiple of 10 mg tablets.

CYCLOPHOSPHamide 150 mg/m² Once daily oral administration
Instructions:

Take each dose with food and a large glass of water, preferably in the morning.

Round dose to closest multiple of 50 mg tablets.

Day: 5

Medication Dose Route Max duration Details
fludarabine * 24 mg/m² Once daily oral administration
Instructions:

Swallow tablets whole with a glass of water, do not crush, chew or break.

Round dose to closest multiple of 10 mg tablets.

CYCLOPHOSPHamide 150 mg/m² Once daily oral administration
Instructions:

Take each dose with food and a large glass of water, preferably in the morning.

Round dose to closest multiple of 50 mg tablets.

Day: 6

Medication Dose Route Max duration Details
pegFILGRASTIM 6 mg subcutaneous injection

Supportive Care Factors

Factor Value
Antiviral prophylaxis for hepatitis B virus: Required for anti–HBc positive patients at risk of reactivation
Antiviral prophylaxis for herpes virus: Routine antiviral prophylaxis recommended
Emetogenicity: Medium to high
Growth factor support: Recommended for primary prophylaxis
Hypersensitivity / Infusion related reaction risk: High - routine premedication recommended
Irradiated blood components: Irradiation of blood components is recommended
Pneumocystis jirovecii pneumonia (PJP) prophylaxis: Routine antibiotic prophylaxis recommended
Tumour lysis syndrome prophylaxis: Tumour lysis syndrome prophylaxis is recommended

Tumour lysis syndrome prophylaxis: Recommended for cycle 1 and consider for subsequent cycles.

References

Hallek, M., K. Fischer, G. Fingerle-Rowson, et al. 2010. "Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial." Lancet 376(9747):1164-1174., PMID: 20888994

Tam, C. S., S. O'Brien, W. Wierda, et al. 2008. "Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia." Blood 112(4):975-980., PMID: 18411418

Eichhorst B., A. Fink, and J. Bahlo et al. 2016. "First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial." Lancet Oncol. 2016 Jul;17(7):928-942., PMID: 27216274

Shanafelt T.D., X.V. Wang, N.E. Kay et al. 2019. "Ibrutinib-Rituximab or Chemoimmunotherapy for Chronic Lymphocytic Leukemia." N Engl J Med. 2019 Aug 1;381(5):432-443., PMID: 31365801

Robak, T., A. Dmoszynska, P. Solal-Celigny, et al. 2010. "Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia." J Clin Oncol 28(10):1756-1765., PMID: 20194844

Badoux, X. C., M. J. Keating, X. Wang, et al. 2011. "Fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy is highly effective treatment for relapsed patients with CLL." Blood 117(11):3016- 3024., PMID: 21245487

Nunes, A. A., A. S. da Silva, K. M. Souza, et al. 2015. "Rituximab, fludarabine, and cyclophosphamide versus fludarabine and cyclophosphamide for treatment of chronic lymphocytic leukemia: A systematic review with meta-analysis." Crit Rev Oncol Hematol 94(3):261-269., PMID: 25797826

Thompson, P. A., et al. (2016). "Fludarabine, cyclophosphamide, and rituximab treatment achieves longterm disease-free survival in IGHV-mutated chronic lymphocytic leukemia." Blood 127(3): 303-309., PMID: 26492934

Benjamini, O., P. Jain, L. Trinh, et al. 2015. "Second cancers in patients with chronic lymphocytic leukemia who received frontline fludarabine, cyclophosphamide and rituximab therapy: distribution and clinical outcomes." Leuk Lymphoma 56(6):1643-1650., PMID: 25308294

Dearden, C. E., S. Richards, M. Else, et al. 2011. "A comparison of the efficacy and safety of oral and intravenous fludarabine in chronic lymphocytic leukemia in the LRF CLL4 trial." Cancer 117(11): 2452- 2460., PMID: 24048793

Howard, D. R., T. Munir, L. McParland, et al. 2017. "Results of the randomized phase IIB ARCTIC trial of low-dose rituximab in previously untreated CLL." Leukemia 31(11): 2416-2425., PMID: 28336937

Munir, T., D. R. Howard, L. McParland, et al. 2017. "Results of the randomized phase IIB ADMIRE trial of FCR with or without mitoxantrone in previously untreated CLL." Leukemia 31(10): 2085-2093., PMID: 28216660

Dartigeas, C., E. Van Den Neste, J. Léger, et al. 2018. "Rituximab maintenance versus observation following abbreviated induction with chemoimmunotherapy in elderly patients with previously untreated chronic lymphocytic leukaemia (CLL 2007 SA): an open-label, randomised phase 3 study." The Lancet Haematology 5(2): e82-e94., PMID: 29275118

Appleby, N., et al. 2018. "Risk adjusted therapy in chronic lymphocytic leukemia: a phase II cancer trials Ireland (CTRIAL-IE [ICORG 07-01]) study of fludarabine, cyclophosphamide, and rituximab therapy evaluating response adapted, abbreviated frontline therapy with FCR in non-del(17p) CLL." Leuk Lymphoma 59(6): 1338-1347., PMID: 28925785

New Zealand Blood Service Transfusion Medicine Handbook Third Edition, 2016 https://www.nzblood.co.nz/assets/Transfusion-Medicine/PDFs/111G122.pdf (accessed 3/2/2022).

Novartis New Zealand Limited Riximyo New Zealand Datasheet 6 July 2020 https://www.medsafe.govt.nz/profs/datasheet/r/riximyoinf.pdf (Accessed 29 March 2022)

Tabernero J, Vyas M, Giuliani R, Arnold D, Cardoso F, Casali PG, Cervantes A, Eggermont AMM, Eniu A, Jassem J, Pentheroudakis G, Peters S, Rauh S, Zielinski CC, Stahel RA, Voest E, Douillard JY, McGregor K, Ciardiello F. Biosimilars: a position paper of the European Society for Medical Oncology, with particular reference to oncology prescribers. ESMO Open. 2017 Jan 16;1(6):e000142. doi: 10.1136/esmoopen-2016-000142., PMID: 28848668

Lyman GH, Balaban E, Diaz M, Ferris A, Tsao A, Voest E, Zon R, Francisco M, Green S, Sherwood S, Harvey RD, Schilsky RL. American Society of Clinical Oncology Statement: Biosimilars in Oncology. J Clin Oncol. 2018 Apr 20;36(12):1260-1265. doi: 10.1200/JCO.2017.77.4893. Epub 2018 Feb 14., PMID: 29443651

Laudati C, Clark C, Knezevic A, Zhang Z, Barton-Burke M. Hypersensitivity Reactions: Priming Practice Change to Reduce Incidence in First-Dose Rituximab Treatment. Clin J Oncol Nurs. 2018 Aug 1;22(4):407-414. doi: 10.1188/18.CJON.407-414., PMID: 30035788

Doyle J, Raggatt M, Slavin M, McLachlan SA, Strasser SI, Sasadeusz JJ, Howell J, Hajkowicz K, Nandurkar H, Johnston A, Bak N, Thompson AJ. Hepatitis B management during immunosuppression for haematological and solid organ malignancies: an Australian consensus statement. Med J Aust. 2019 Jun;210(10):462-468. doi: 10.5694/mja2.50160. Epub 2019 May 19., PMID: 31104328

Medicines and Hepatitis B Reactivation Prescriber Update 38(1): 2-3 March 2017. https://medsafe.govt.nz/profs/PUArticles/March2017/MedicinesAndHepatitisB.htm

Rituximab and Hepatitis B Reactivation Prescriber Update 34(3):27 September 2013 . https://www.medsafe.govt.nz/profs/PUArticles/Sept2013RituximabHepB.htm  

* The medicines, doses, combinations, and schedule in this treatment regimen have been carefully reviewed against international best practice guidelines by specialists in medical oncology around New Zealand and this advice has been accepted for publication by Te Aho o Te Kahu (the Cancer Control Agency). Sometimes medicines that are used in routine clinical practice have not been through a formal review process by the NZ Medicines Regulator Medsafe and are therefore considered unapproved or off-label. These medicines are legally able to be prescribed through sections 25 and 29 of the Medicines Act and by obtaining informed consent from patients. All treatment regimens listed on this website have been through robust peer review and are considered an accepted standard of care, whether prescribed through sections 25 or 29 or carrying formal Medsafe Approval.

s29: This symbol indicates that some formulations of the associated medicine are legally only able to be prescribed under section 29 of the Medicines Act. You can see which formulations are section 29 by hovering over the s29 symbol. You can access full medication details from the New Zealand Formulary by clicking on the medication name. Each clinician retains full responsibility for ensuring they have complied with all relevant obligations and requirements of section 29 including obtaining informed patient consent prior to prescribing the applicable medicine.