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A - Regimen Name

FC(PO) Regimen
Fludarabine (oral)-Cyclophosphamide (oral)


Disease Site
Hematologic - Lymphoma - Non-Hodgkin's Low Grade

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.


Rationale and Uses

Treatment of recurrent follicular or other non-Hodgkin’s indolent B-cell lymphoma 


Supplementary Public Funding

cyclophosphamide
ODB - General Benefit (cyclophosphamide - oral tablets) (ODB Formulary)

 
B - Drug Regimen

fludarabine
25 mg /m² PO Days 1 to 5
(This drug is not currently publicly funded for this regimen and intent)
(Outpatient prescription in multiples of 10 mg tablets)
cyclophosphamide
150 mg /m² PO Days 1 to 5

(Outpatient prescription in multiples of 25 or 50 mg tablets)

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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:

Moderate – Consider prophylaxis daily

Other Supportive Care:

Also refer to CCO Antiemetic Recommendations.

Consider prophylactic growth factor support, antiviral and PCP prophylaxis (according to local practice).

If high volume disease, consider prophylaxis for tumour lysis

 
E - Dose Modifications

Doses should be modified according to the protocol by which the patient is being treated. The following recommendations have been adapted from clinical trials or product monographs and could be considered.

 

Dosage with toxicity

Toxicity
Fludarabine
(% previous dose)                   
Cyclophosphamide
(% previous dose)
Febrile Neutropenia;
Grade 4 myelosuppression  ≥ 7 days; Thrombocytopenic bleeding;
1-2 week delay prior cycle
 
75% or G-CSF (for isolated neutropenia*
75% or G-CSF (for isolated neutropenia)*
Grade 3 non-hematologic / organ
 
75%*
75%*
Any grade autoimmune, neurotoxicity, pneumonitis, pure red cell aplasia, > 2 week delay prior cycle, or progressive disease
 
Discontinue
Discontinue
*Do not retreat until non-hematologic / organ toxicity recovered to ≤ grade 2, ANC to ≥ 1 x 109/L and platelets ≥ 80 x 109/L (or to baseline levels)



Hepatic Impairment

Bilirubin

 

AST / ALT

Fludarabine

(% usual dose)

Cyclophosphamide

(% usual dose)

1-2 x ULN

 

 

No data available;

use with caution

No change

>2-4 X ULN

and/or

>2-4 X ULN

Caution

> 4 x ULN

and/or

> 4 x ULN

Caution

 


Renal Impairment

Creatinine Clearance (mL/min)

 

Fludarabine

(% usual dose)

Cyclophosphamide

(% usual dose)

>50 - 70

50%

100%

30 - 50

50%

75%

10 - <30

Discontinue

 

75%

<10

Use with extreme caution or Discontinue


 
F - Adverse Effects

Refer to fludarabine, cyclophosphamide drug monograph(s) for additional details of adverse effects. 


Most Common Side Effects

Less Common Side Effects, but may be Severe or Life-Threatening

  • Myelosuppression ± bleeding
  • Infection; including opportunistic (may be severe)
  • GI (nausea/vomiting, diarrhea, anorexia)
  • Fever
  • ↑ LFTs
  • Fatigue
  • Rash (may be severe)
  • Visual changes
  • Cystitis
  • Autoimmune disorders (e.g. hemolytic anemia, TTP)
  • Encephalopathy, CNS toxicity (e.g. seizures, confusion, agitation)
  • Pneumonitis
  • Cardiotoxicity, arrhythmia
  • Arterial thromboembolism
  • Venous thromboembolism
  • Secondary malignancies
  • Tumour lysis syndrome
  • Nephrotoxicity
  • Pancreatitis
  • Rhabdomyolysis
 
G - Interactions

Refer to fludarabine, cyclophosphamide drug monograph(s) for additional details

 
H - Drug Administration and Special Precautions

Refer to fludarabine, cyclophosphamide drug monograph(s) for additional details

 
I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Recommended Clinical Monitoring

  • CBC; baseline and at each visit
  • Liver and renal function tests; baseline and at each visit
  • Clinical toxicity assessment (including infection, bleeding, hypersensitivity, cystitis, pulmonary, skin, GI and CNS effects); at each visit
  • Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version


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J - Administrative Information

Outpatient prescription for home administration


 
K - References

Eve HE, Linch D, Qian W, et al. Toxicity of fludarabine and cyclophosphamide with or without rituximab as initial therapy for patients with previously untreated mantle cell lymphoma: results of a randomised phase II study. Leuk Lymphoma. 2009 Feb;50(2):211-5.

Fabbri A, Lenoci M, Gozzetti A, et al. Low-dose oral fludarabine plus cyclophosphamide as first-line treatment in elderly patients with indolent non-Hodgkin lymphoma. Br J Haematol. 2007 Oct;139(1):90-3.

Fludarabine and cyclophosphamide drug monographs, Cancer Care Ontario. 

Tam CS, Wolf MM, Januszewicz EH, et al.  Fludarabine and cyclophosphamide using an attenuated dose schedule is a highly effective regimen for patients with indolent lymphoid malignancies.  Cancer 2004;100:2181–9.

Eucker J,Schille C,Schmid P, et al.  The combination of fludarabine and cyclophosphamide results in a high remission rate with moderate toxicity in low-grade non-Hodgkin’s lymphomas. Anti-Cancer Drugs 2002;13:907–13.

June 2019 Updated emetic risk category


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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.