You are using an outdated browser. We suggest you update your browser for a better experience. Click here for update.
Close this notification.
Skip to main content Skip to search

FC(PO)+R

Cancer Type: Hematologic, Leukemia - Chronic Lymphocytic (CLL)  Intent: Palliative
Regimen Category: Evidence-informed
Funding:
New Drug Funding Program
    Rituximab - Previously Untreated Chronic Lymphocytic Leukemia
New Drug Funding Program
    Rituximab - Second Line - Chronic Lymphocytic Leukemia
ODB Limited Use
    fludarabine - For the first-line treatment of CLL in combination with rituximab (tablets; with or without cyclophosphamide)
ODB Limited Use
    fludarabine - For second-line therapy of patients with CLL who have failed or are intolerant to chlorambucil (tablets)
New Drug Funding Program
    Rituximab (SC) - Previously Untreated Chronic Lymphocytic Leukemia
A - Regimen Name

FC(PO)+R Regimen
Fludarabine (oral)-Cyclophosphamide (oral)-Rituximab


Disease Site
Hematologic - Leukemia - Chronic Lymphocytic (CLL)

Intent
Palliative

Regimen Category
Evidence-informed :

Regimen is considered appropriate as part of the standard care of patients; meaningfully  improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR).  Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.

This Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph. Full regimen monographs will be published for each ST-QBP regimen as they are developed.


Rationale and Uses

Treatment of anti-CD20 antibody-naive previously untreated or second-line relapsed or refractory CLL patients, in whom fludarabine-based therapy is considered appropriate. There is insufficient evidence for the use of maintenance rituximab in CLL patients.   


Supplementary Public Funding

riTUXimab
New Drug Funding Program (Rituximab - Previously Untreated Chronic Lymphocytic Leukemia)

riTUXimab
New Drug Funding Program (Rituximab - Second Line - Chronic Lymphocytic Leukemia)

fludarabine
ODB Limited Use (fludarabine - For the first-line treatment of CLL in combination with rituximab (tablets; with or without cyclophosphamide))

fludarabine
ODB Limited Use (fludarabine - For second-line therapy of patients with CLL who have failed or are intolerant to chlorambucil (tablets))

riTUXimab (subcut)
New Drug Funding Program (Rituximab (SC) - Previously Untreated Chronic Lymphocytic Leukemia)

riTUXimab (subcut)
New Drug Funding Program (Rituximab (SC) - Second Line - Chronic Lymphocytic Leukemia)

cyclophosphamide
ODB - General Benefit (cyclophosphamide - oral tablets)

 
B - Drug Regimen

Cycle 1:  All patients must receive their first dose of rituximab by IV infusion.

riTUXimab
375 mg /m² IV * Day 1

In clinical trials, cycle 1 rituximab was given the day prior to FC

fludarabine
25 mg /m² PO Days 1 to 5

(Outpatient prescription in 10 mg tablets)

cyclophosphamide
150 mg /m² PO Days 1 to 5

(Outpatient prescription in 25 mg or 50 mg tablets)


Cycle 2 and onwards: (For a total of 6 cycles, including initial IV rituximab cycle(s) )

Rituximab IV:

riTUXimab
500 mg /m² IV * Day 1


OR

Rituximab (subcut): 
The subcutaneous formulation must only be given at the second or subsequent cycles, and only after at least 1 full rituximab IV dose.

riTUXimab (subcut)
1600** mg Subcut Day 1

 

PLUS FC(PO) chemotherapy:

fludarabine
25 mg /m² PO Days 1 to 5

(Outpatient prescription in 10 mg tablets)

cyclophosphamide
150 mg /m² PO Days 1 to 5

(Outpatient prescription in 25 mg or 50 mg tablets)

* Consider slower infusion rate or split dosing over days 1-2 (± corticosteroids) for any cycle where high tumour load or WBC > 25 x 109/L. 

** Note: Rituximab subcut dosing is higher in CLL compared to other indications. Ensure the proper dose is administered.

back to top
 
C - Cycle Frequency

REPEAT EVERY 28 DAYS

For a usual total of 6 cycles unless disease progression or unacceptable toxicity occurs

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

Minimal
Consider prophylaxis daily for cyclophosphamide PO

Other Supportive Care:

Also refer to CCO Antiemetic Recommendations.

Consider antiviral and PCP prophylaxis

Rituximab premedication:

  • Acetaminophen 650mg PO
  • Diphenhydramine 50mg PO/IV
  • If high volume disease, consider steroids and prophylaxis for tumour lysis

HBsAg positive patients should receive antiviral prophylaxis during and after rituximab. HBsAg negative, but HBcAb positive patients should be considered for antiviral prophylaxis and be closely monitored for viral reactivation by a HBV expert.

 
J - Administrative Information

FC(PO):  Outpatient prescription for home administration


Approximate Patient Visit
1-5 hours
Pharmacy Workload (average time per visit)
28.643 minutes
Nursing Workload (average time per visit)
84.167 minutes
 
K - References

Assouline S, Buccheri V, Delmer A, et al.  Pharmacokinetics, safety, and efficacy of subcutaneous versus intravenous rituximab plus chemotherapy as treatment for chronic lymphocytic leukaemia (SAWYER): a phase 1b, open-label, randomised controlled non-inferiority trial.  Lancet Haematol 2016;3(3):e128-38.

Cazin B, Divine M, Leprêtre S, et al. High efficacy with five days schedule of oral fludarabine phosphate and cyclophosphamide in patients with previously untreated chronic lymphocytic leukaemia. Br J Haematol. 2008 Oct;143(1):54-9.

Hallek M, Fischer K, Fingerle-Rowson G, et al.  Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial.  Lancet 2010;376(9747):1164-74. 

Hendry L, Bowen A, Matutes E, et aL.  Fludarabine, cyclophosphamide and mitoxantrone in relapsed or refractory chronic lymphocytic leukemia and low grade non-Hodgkin's lymphoma.  Leuk Lymphoma 2004 May;45(5):945-50.

Hillmen P, Cohen DR, Cocks K, et al.  A randomized phase II trial of fludarabine, cyclophosphamide and mitoxantrone (FCM) with or without rituximab in previously treated chronic lymphocytic leukaemia.  Br J Haematol. 2011 Mar;152(5):570-8.

Keating MJ, O’Brien S, Albitar M, et al. Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. J Clin Oncol 2005; 23: 4079-88.

Laurenti L, De Padua L, Tarnani M, et al. Comparison between oral and intravenous fludarabine plus cyclophosphamide regime as front-line therapy in patients affected by chronic lymphocytic leukaemia: influence of biological parameters on the clinical outcome. Ann Hematol. 2011 Jan;90(1):59-65.

Robak T, Dmoszynska A, Solal-Celigny P, et al. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia. J Clin Oncol 2010; 28: 1756-65.

Tam CS, O’Brien S, Wierda W, et al. Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia. Blood 2008; 112(4): 975-80.


PEBC Advice Documents or Guidelines

June 2019 Updated emetic risk category


back to top
 
M - Disclaimer

Regimen Abstracts
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. Such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph.  Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.