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regimen-monograph
CYCL(PO)
Intent
Palliative
Regimen Category
Evidence-Informed
Funding Program
ODB - General Benefit
cyclophosphamide - oral tablets
Drugs Used
A - Regimen Name
CYCL(PO) Regimen
Cyclophosphamide (oral)
Disease Site
Hematologic - Multiple Myeloma
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
Patients with previously treated myeloma (including with prior HDCT/ASCT) who are candidates for further therapy and whose disease is sensitive to alkylating agents (≥ one year from last alkylator).
Supplementary Public Funding
B - Drug Regimen
| cyclophosphamide | 500 mg | PO | Every 7 days |
|
OR |
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| cyclophosphamide | 50 mg | PO | Daily |
|
(Outpatient prescription in multiples of 25mg & 50mg tablets) May be used with or without prednisone (15 mg PO daily OR 50-100 mg PO every 2 days have been used in some clinical trials) |
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D - Premedication and Supportive Measures
Antiemetic Regimen:
Low (daily dose)
Moderate (weekly dose)
Other Supportive Care:
Also refer to CCO Antiemetic Summary
E - Dose Modifications
Doses should be modified according to the protocol by which the patient is being treated.
Daily schedule dose levels: 50 mg daily, 25 mg daily, 25 mg on alternate days
Weekly schedule dose levels: 500 mg weekly, 400 mg weekly, 300 mg weekly
Dosage with toxicity
Toxicity (counts x 109/L) |
Cyclophosphamide Dose* |
ANC 1 to 1.5 or platelets 75 to 100
|
Continue with 1 dose level reduction |
ANC < 1 or platelets < 75 |
Hold; may consider reducing 1 dose level when restart |
Grade 4 ANC or platelets, febrile neutropenia or thrombocytopenic bleeding |
Hold; reduce 1 dose level |
Grade 3 non-hematologic / organ |
Hold; reduce 1 dose level |
Grade 4 non-hematologic /organ |
Discontinue |
Pneumonitis |
Hold, investigate and if confirmed, discontinue |
Hematuria |
Hold until resolution |
* Do not retreat until ANC > 1 x 109/L, platelets > 75 x 109/L and other toxicity recovered to ≤ grade 2. |
|
Hepatic Impairment
|
Bilirubin
|
Cyclophosphamide (% previous dose) |
|
1-2 x ULN
|
100%
|
|
2-4 x ULN
|
Caution
|
|
> 4 x ULN
|
Caution
|
Renal Impairment
Renal failure may lead to the reduced excretion of cyclophosphamide metabolites and increased toxicity. Significant falls in clearance (25-80%) with increased exposure have been documented in patients with renal impairment. Cyclophosphamide is hemodialysable.
|
Creatinine Clearance (mL/min)
|
Cyclophosphamide (% previous dose)
|
|
> 50
|
100%
|
|
10 - 50
|
75%
|
|
< 10
|
Use with extreme caution or discontinue
|
F - Adverse Effects
Refer to cyclophosphamide drug monograph(s) for additional details of adverse effects
| Most Common Side Effects | Less Common Side Effects, but may be |
|
|
G - Interactions
Refer to cyclophosphamide drug monograph(s) for additional details
- Use with caution with allopurinol, thiazide diuretics and ACE inhibitors as increased myelosuppression has been reported.
- Avoid concomitant use with lovastatin as increased rhabomyolysis has been reported.
- Drugs which inhibit CYP3A4 (e.g. azole antifungals) and grapefruit juice may increase toxicity. Avoid grapefruit juice 48 hours before and on the day of receiving cyclophosphamide.
- Prolonged post-operative apnea may occur with depolarizing muscle relaxants (e.g. succinylcholine). Notify anesthesiologist prior to use; succinylcholine dose modification may be required.
- Use with caution with nephrotoxic drugs (e.g. aminoglycosides, methotrexate) due to additive nephrotoxicity.
H - Drug Administration and Special Precautions
Refer to cyclophosphamide drug monograph(s) for additional details
Administration:
Oral tablets should be administered as a single dose in the morning, with or without food. Hydration is recommended (8 to 10 (8oz) glasses of fluid per day).
Special precautions:
- Avoid in patients with severe hepatic or renal impairment, patients with severe myelosuppression and/or immunosuppression, patients with active infection, particularly varicella zoster infection, and patients with urinary outflow obstruction.
- Avoid live or live-attenuated vaccines as use may result in serious or fatal infections in immunocompromised patients.
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
- Renal function tests and urinalysis; baseline and at each visit
- Clinical toxicity assessment (gastrointestinal, cystitis, infection, bleeding, thromboembolism, cardiac or pulmonary toxicity); at each visit
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Suggested Clinical Monitoring
- Liver function tests; baseline and as clinically indicated
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K - References
Brandes LJ, Israels LG. Weekly low-dose cyclophosphamide an alternate-day prednisone: an effective low toxicity regimen for advanced myeloma. Eur J Haematol 1987;39:362-8.
Cyclophosphamide drug monograph, Cancer Care Ontario.
Trieu T, Trudel, S, Pond GR, et al. Weekly cyclophosphamide and alternate-day Prednisone: an effective, convenient, and well-tolerated oral treatment for relapsed multiple myeloma after autologous stem cell transplantation. Mayo Clin Proc 2005;80(12):1578-82.
Wilson K, Shelly W, Belch A et al. Weekly cyclophosphamide and alternate-day prednisone: an effective secondary therapy in multiple myeloma. Cancer Treat Rep 1987 Oct; 71(10): 981-2.
October 2017 Replaced regimen category with evidence-informed
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.
Last Updated: July 21, 2026
