Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.
CVP+R
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.
Treatment of follicular lymphoma or other indolent histology, CD20-positive B-cell lymphoma (excluding small lymphocytic lymphoma (SLL), chronic lymphocytic leukemia (CLL)), in patients who:
- Have not received previous treatment with rituximab for indolent B-cell lymphoma
- Have previously received rituximab (including combination rituximab-chemotherapy and/or rituximab monotherapy or maintenance rituximab) and have sustained a response and remained disease-free for at least 6 months after the last dose of rituximab
Refer to the NDFP eligibility forms for detailed funding criteria.
prednisone
ODB - General Benefit
(prednisone)
(ODB Formulary
)
riTUXimab (subcut)
New Drug Funding Program
(Rituximab (Biosimilar IV) and Rituximab SC in Combination with Chemotherapy - Indolent B-cell Lymphoma)
riTUXimab (subcut)
New Drug Funding Program
(Rituximab (Biosimilar IV) and Rituximab SC - Retreatment - Indolent Lymphoma)
(in combination with chemotherapy
)
riTUXimab
New Drug Funding Program
(Rituximab (Biosimilar IV) and Rituximab SC in Combination with Chemotherapy - Indolent B-cell Lymphoma)
(NDFP Website)
riTUXimab
New Drug Funding Program
(Rituximab (Biosimilar IV) and Rituximab SC - Retreatment - Indolent Lymphoma)
(NDFP Website)
(in combination with chemotherapy
)
Note: Different rituximab products are NOT INTERCHANGEABLE.
Cycle 1: All patients must receive their first dose of rituximab by IV infusion
| prednisone | 100 mg | PO daily | Days 1 to 5* |
|
*(On Day 1 to be given as part of premedication before riTUXimab) |
|||
| riTUXimab | 375 mg /m² | IV | Day 1 |
| vinCRIStine | 1.4 mg /m² | IV (max 2 mg) | Day 1 |
| cyclophosphamide | 750 mg /m² | IV | Day 1 |
|
Cycle 2 and onwards: (For a usual total of 6-8 cycles including initial IV rituximab cycle(s) ) Rituximab IV: |
|||
| riTUXimab | 375 mg /m² | IV | Day 1 |
|
Rituximab subcutaneous: |
|||
| riTUXimab (subcut) | 1400 mg | Subcut | Day 1 |
|
|
|||
| prednisone | 100 mg | PO daily | Days 1 to 5* |
|
*(On Day 1 to be given as part of premedication before riTUXimab) |
|||
| vinCRIStine | 1.4 mg /m² | IV (max 2 mg) | Day 1 |
| cyclophosphamide | 750 mg /m² | IV | Day 1 |
REPEAT EVERY 21 DAYS for a usual total of 6-8 cycles in the absence of unacceptable toxicity or disease progression.
For patients who responded to induction therapy, and were rituximab-naïve prior to induction, refer to maintenance rituximab regimen - RITU(MNT) or RITU(MNT-SC).
Moderate
Other Supportive Care:
- Also refer to CCO Antiemetic Recommendations.
- Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.
- If high volume disease, consider prophylaxis for tumour lysis.
Premedication (prophylaxis for infusion reactions):
Administer at least 30 minutes prior to rituximab:
- Oral antipyretic (e.g. acetaminophen)
- H1-receptor antagonist (e.g. diphenhydramine)
- Give day 1 prednisone as part of pre-medication before rituximab.
- In patients receiving subcut rituximab who experienced adverse effects with pre-medications, the omission of pre-medications can be considered.
See premedication and monitoring sections for supportive care, screening and monitoring recommendations. Doses should be modified according to the protocol by which the patient is being treated.
Dosage with toxicity
| Toxicity | Vincristine1 (% previous dose) | Cyclophosphamide1 (% previous dose) | Rituximab IV or Subcut1,2(% previous dose) |
| Grade 4 hematological, febrile neutropenia, bleeding | 100% | 75% or G-CSF for low ANC | 100% |
| Grade 3 non-hematological toxicity | 100% | 75% | 100% or delay |
| Neurotoxicity | Mild: 67%; Moderate: Hold until recovery, then ↓ 50%; Severe: Discontinue |
100% | 100% |
| Cystitis | 100% | Hold until resolution | 100% |
| Grade 4 organ toxicity | Discontinue | Discontinue | Discontinue |
|
Discontinue | Discontinue | Discontinue |
2Missed or delayed doses may be administered at a later time point, based on physician’s discretion
Management of Rituximab Administration-Related Reactions:
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
| Grade | Management | Re-challenge |
| 1 or 2 |
Restart:
|
|
| 3 or 4 |
|
|
Hepatic Impairment
| Bilirubin | Vincristine* (% previous dose) |
Cyclophosphamide (% previous dose) |
Rituximab |
| 1 – 2 x ULN | 50% | 100% | No dose adjustment needed; discontinue if hepatitis |
| 2 – 4 x ULN | 25% | Caution | |
| > 4 x ULN | OMIT | Caution |
*Also consider dose modification for vincristine for severe increase in transaminases.
Renal Impairment
| Creatinine Clearance (mL/min) | Vincristine (% previous dose) |
Cyclophosphamide (% previous dose) |
Rituximab |
|
>50
|
No dose adjustment required. |
100%
|
No dose adjustment required |
|
10-50
|
May consider 75%
|
||
|
< 10 |
50%; use with caution and monitor closely |
Dosage in the Elderly
No dose adjustment required. Exercise caution as older patients are more likely to experience serious adverse events (including cardiac, pulmonary, neurotoxicity or other grade 3/4 toxicity).
Refer to riTUXimab, riTUXimab (SC), vinCRIStine, cyclophosphamide drug monograph(s) for additional details of adverse effects
|
Very common (≥ 50%) |
Common (25-49%) |
Less common (10-24%) |
Uncommon (< 10%), but may be severe or life-threatening |
|
|
|
|
Refer to riTUXimab, riTUXimab (SC), vinCRIStine, cyclophosphamide drug monograph(s) for additional details
- Consider withholding antihypertensive medication 12 hours prior to and during rituximab administration.
- Avoid combination of vincristine and verapamil or nifedipine; monitor closely if given concurrently.
- Avoid concurrent alcohol use with cyclophosphamide; may ↑ cyclophosphamide-induced nausea and vomiting; reduced anti-tumour activity has been observed in animal studies
- Caution with use of CYP3A4 inhibitors and cyclophosphamide; avoid grapefruit for 48 hours before and on day of cyclophosphamide.
- Monitor serum phenytoin levels when used with vincristine, and adjust phenytoin dose as needed.
Refer to riTUXimab, riTUXimab (SC), vinCRIStine, cyclophosphamide drug monograph(s) for additional details
Note: Different rituximab products are NOT INTERCHANGEABLE.
Administration
Rituximab IV and subcutaneous formulations are not interchangeable. The dosing and concentrations of these products are different.
Refer to Safety Considerations for the Implementation of Subcutaneous Rituximab Formulation.
Rituximab should be administered in a setting where full resuscitation facilities are immediately available, and under the close supervision of someone experienced and capable of dealing with severe infusion-related reactions.
riTUXimab (IV)
- DO NOT administer as an IV push or bolus.
- Dilute to a final concentration of 1-4 mg/mL in normal saline or D5W.
- To avoid foaming, gently invert the bag to mix the solution.
- Do not admix with other drugs.
- Administer rituximab through a dedicated line.
- Compatible with PVC or polyethylene bags.
Infusion rates:
First infusion:
-
Recommended to be administered over a graduated rate: initial rate of 50 mg/h, then escalate rate in 50 mg/h increments every 30 minutes, to a maximum of 400 mg/h (about 4.25 hours in total).
Subsequent infusions:
-
If no severe infusion reaction (grade 3 or 4) occurred with the first cycle, a rapid infusion of IV rituximab over a total of 90 minutes can be initiated with cycle 2 (20% of the dose in the first 30 min then the remaining 80% over 60 min).
-
OR initial rate of 100 mg/h, then escalate rate in 100 mg/h increments every 30 minutes, to a maximum of 400 mg/h as tolerated (about 3.25 hours in total).
-
Alternatively, subcutaneous administration of rituximab can be considered starting with cycle 2.
When bulky disease present or WBC > 25-50 x 109/L, consider:
- A slower infusion rate, or
- Split dosing over days 1-2, or
- Delaying rituximab treatment until chemotherapy has reduced the lymphocyte count
riTUXimab (SC):
Refer to Safety Considerations for the Implementation of Subcutaneous Rituximab Formulation
- Rituximab SC must not be self-administered.
- Rituximab SC is given subcutaneously into the abdominal wall only. Do not give in areas where the skin is red, tender, hard, bruised, or where there are moles or scars.
- Non-Hodgkin’s lymphoma: Give SC over approximately 5 minutes
- Observe for at least 15 minutes after administration.
- Cold compresses and topical steroids may be helpful for local cutaneous reactions.
- If there are other SC medications, they should be given at separate sites.
- Compatible with polypropylene or polycarbonate syringes.
vinCRIStine:
FOR INTRAVENOUS USE ONLY. Vincristine is lethal if given intrathecally. No successful antidotes have been described. Syringes containing this product should be labelled “WARNING – FOR INTRAVENOUS USE ONLY. FATAL if given by other routes.”
- Direct IV push not recommended, due to risk of inadvertent intrathecal administration.
- For intermittent IV use, may mix in small volume minibag (ie. 50mL NS or D5W for adults).
- Infuse IV via gravity. Infusion pumps should not be used peripherally, since they deliver infusions at higher pressures and may continue to infuse when extravasation occurs.
- During the infusion, suggest nurse to remain present with the patient to observe the IV site for extravasation.
Cyclophosphamide:
- Oral hydration is strongly encouraged; for IV cyclophosphamide: 2-3 L of fluid/day; poorly hydrated patients may need more IV hydration.
- Inadequate total hydration may result in dose-related hemorrhagic cystitis.
- Patients should be encouraged to empty their bladder frequently to minimize dwell times.
- Infuse in 250 mL sodium chloride 0.9% over 30 minutes.
- Morning administration of cyclophosphamide is recommended, to decrease the amount of drug dwelling in the bladder overnight.
- For IV infusion, may reconstitute cyclophosphamide with sodium chloride 0.9% or sterile water for injection before further dilution.
- Do not reconstitute or dilute with benzyl alcohol-containing solutions (i.e. Bacteriostatic sodium chloride), since it may catalyse the decomposition of cyclophosphamide
- Avoid the use of aluminum-containing preparation and administration equipment, since darkening of aluminum and gas production have been reported.
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
Contraindications:
- Patients who have a hypersensitivity to any of the drug(s) or any of its components, or known hypersensitivity and anaphylactic reactions to proteins of similar mouse or human origin, to Chinese Hamster Ovary (CHO) cell proteins, or to rituximab, cyclophosphamide, vincristine, prednisone and its components
- Patients who have or have had PML, have active and/or severe infections, active hepatitis B, or severely immunocompromised (e.g. AIDS patients with very low CD4 or CD8 counts).
- Avoid the use of live vaccines.
- Vincristine intrathecal administration is absolutely contraindicated.
- (vincristine) patients with the demyelinating form of Charcot-Marie-Tooth Syndrome, childhood polio or with hypersensitivity to vinca alkaloids.
- (doxorubicin) Patients with severe myocardial insufficiency, arrhythmias or history of cardiac disease or recent myocardial infarction
- (doxorubicin) Patients with previous treatment with maximum cumulative doses of doxorubicin, other anthracyclines or anthracenediones
- (cyclophosphamide) patients with urinary outflow obstruction
Precautions:
- Exercise caution in patients with a history of recurring or chronic infections or with underlying conditions which may further predispose patients to serious infection. Patients may have increased risk of infection following rituximab treatment.
- Prior to starting rituximab in HBV seropositive patients, consultation with a liver disease expert is recommended to determine ongoing monitoring of HBV reactivation and its management.
- Exercise caution in patients with neutrophil counts < 1.5 x 109/L and/or platelets < 75 x 109/L due to limited experience with rituximab in this patient group.
- Use rituximab with extreme caution in patients with pre-existing cardiovascular disease or in patients with high tumour burden. Consider steroids ± rituximab slow infusions or infusions split over 2 days for patients with bulky disease or > 25 x 109/L circulating malignant cells.
- Use rituximab with caution in patients with pulmonary insufficiency or lung tumour infiltration, and in patients with myelosuppression.
- Reduced immunogenicity may occur with use of inactivated vaccines.
- Use vincristine with caution with other neuromuscular disorders, neurotoxic/ototoxic drugs, in leukopenia, complicating infection, or and in patients with Guillain-Barre Syndrome.
- Vincristine should not be given to patients who are receiving radiation that includes liver portals.
- Use cyclophosphamide with caution in patients with adrenal insufficiency or when used in combination with neuromuscular blockers.
Pregnancy / Lactation:
- This regimen is not recommended for use in pregnancy. Adequate contraception should be used by patients and their partners while on treatment and after the last treatment dose. Recommended methods and duration of contraception may differ depending on the treatment. Refer to the drug monograph(s) for more information.
- Breastfeeding is not recommended during this treatment and after the last treatment dose. Refer to the drug monograph(s) for recommendations after the last treatment dose (if available).
- Effects on fertility: Yes
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.
Recommended Clinical Monitoring
- CBC; baseline and before each cycle
- Liver function tests; baseline and before each cycle
- Renal function tests; baseline and before each cycle
- Electrolytes, baseline and as clinically indicated
- Monitor patients during and for at least 15 minutes after each rituximab dose, longer in patients at higher risk of hypersensitivity reactions
- Clinical assessment of hypersensitivity/infusion reactions, local toxicity, tumour lysis syndrome, infection, bleeding, GI, pulmonary, skin, CNS, neurologic, cardiovascular and cystitis; at each visit
-
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Suggested Clinical Monitoring
- Monitor cardiovascular symptoms in patients who have cardiac conditions or recurrent cardiac events with rituximab; At each visit
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Cyclophosphamide, vincristine drug monographs, Cancer Care Ontario.
Davies A, Merli F, Mihaljević B, et al. Efficacy and safety of subcutaneous rituximab versus intravenous rituximab for first-line treatment of follicular lymphoma (SABRINA): a randomised, open-label, phase 3 trial. Lancet Haematol. 2017 Jun;4(6):e272-e282.
Hochster H, Weller E, Gascoyne RD, et al. Maintenance Rituximab After Cyclophosphamide, Vincristine, and Prednisone Prolongs Progression-Free Survival in Advanced Indolent Lymphoma: Results of the Randomized Phase III ECOG1496 Study. JCO 2009; 27: 1607-14.
Marcus R, Imrie, K, Solal-Celigny P, et al. Phase III Study of R-CVP Compared With Cyclophosphamide, Vincristine, and Prednisone Alone in Patients With Previously Untreated Advanced Follicular Lymphoma. JCO 2008: 26; 4579-86.
Marcus, R., et al., CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood, 2005. 105(4): p. 1417-23.
Salar A, Casao D, Cervera M, et al. Rapid infusion of rituximab with or without steroid-containing chemotherapy: 1-yr experience in a single institution. Eur J Haematol 2006: 77: 338–340
Sehn LH, Donaldson J, Filewich A, et al. Rapid Infusion Rituximab in Combination with Steroid Containing Chemotherapy Can Be Given Safely and Substantially Reduces Resource Utilization. Blood 2004; 104(11): A1407.
November 2023 Modified Pregnancy/breastfeeding section
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.