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.
RAMU
Gastric / Stomach
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.
For the treatment of advanced or metastatic gastric cancer or gastro-esophageal junction adenocarcinoma, with disease progression on or after prior platinum and fluoropyrimidine chemotherapy.
| ramucirumab | 8 mg /kg | IV | Day 1 |
| (This drug is not currently publicly funded for this regimen and intent) | |||
Minimal
- 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.
Premedications (prophylaxis for infusion reactions):
- H1-receptor antagonist IV (e.g. diphenhydramine)
For patients who experienced a grade 1 or 2 infusion reaction:
- H1-receptor antagonist IV (e.g. diphenhydramine)
- Dexamethasone IV (or equivalent)
- Acetaminophen
Doses should be modified according to the protocol by which the patient is being treated.
Dosage with toxicity
| Dose level | Ramucirumab dose (mg/kg) |
| 0 | 8 |
| -1 | 6 |
| -2 | 5 |
|
Toxicity |
Severity |
Ramucirumab dose |
|
Hypertension |
Grade 3 or 4 |
Hold until controlled with antihypertensive therapy. Discontinue if cannot be controlled. |
|
Proteinuria |
1st occurrence urine protein ≥ 2 g/24 hours |
Hold* and restart at 1 dose level ↓ once urine protein < 2 g/24 hours. |
|
2nd occurrence urine protein ≥ 2 g/24 hours |
||
|
3rd occurrence OR urine protein > 3 g/24 hours OR nephrotic syndrome |
Discontinue |
|
|
Delayed wound healing |
n/a |
Hold for at least 4 weeks prior to scheduled surgery until the wound is fully healed. Discontinue if wound healing complications arise. |
| Cardiac failure | Any | Consider hold. Discontinue if severe or as clinically indicated. |
|
Arterial thromboembolism Life-threatening VTE Bleeding |
Grade 3 or 4 |
Discontinue |
|
GI perforation Fistula PRES |
Any |
Discontinue |
| Other non-hematologic toxicity | Grade 4 | Discontinue |
*In the clinical trial, doses were held up to 2 weeks. If urine protein does not return to < 2 g/24 hours, discontinue.
Management of Infusion-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
New onset or worsening ascites, encephalopathy or hepatorenal syndrome can occur in patients with Child-Pugh B or C cirrhosis. Treat only if potential benefit outweighs risk in these patients. No studies have been conducted for patients with hepatic impairment.
Renal Impairment
Population pharmacokinetic analysis suggests no dosage adjustment needed for mild to moderate renal impairment. No data available for patients with CrCl < 30 ml/min.
Dosage in the Elderly
No dose adjustment required. No overall differences in safety or effectiveness were observed between patients ≥65 years compared with younger patients.
Dosage based on ethnicity
Higher incidences of grade 3 proteinuria and nephrotic syndrome were reported in Asian patients living in East Asia compared to Caucasian patients.
Refer to ramucirumab drug monograph(s) for additional details of adverse effects
|
Common (25-49%) |
Less common (10-24%) |
Uncommon (< 10%), but may be severe or life-threatening |
|
|
|
Refer to ramucirumab drug monograph(s) for additional details
- Use with caution and monitor with other anti-angiogenic drugs and bisphosphonates; risk of ONJ may be increased.
Refer to ramucirumab drug monograph(s) for additional details
Administration:
- Administer as IV infusion only. DO NOT administer as IV push or bolus.
- Withdraw required volume and transfer into an empty IV container.
- Dilute with normal saline to a total volume of 250 mL. DO NOT use dextrose as a diluent.
- Gently invert container to mix. DO NOT shake.
- Infuse IV over approximately 60 minutes (maximum rate 25 mg/min) using a separate infusion line, with a protein sparing 0.22 micron filter.
- Flush the line with normal saline at the end of the infusion.
- DO NOT dilute or co-administer with other electrolytes or medications.
- Refrigerate unopened vials in original carton (2-8°C). Protect from light and DO NOT freeze.
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
Contraindications:
- Hypersensitivity to ramucirumab or any of the components in the formulation
Warnings/Precautions:
- Treat only if potential benefit outweighs risk in patients with Child-Pugh Class B or C cirrhosis as clinical deterioration has been reported.
- Use with caution in patients with known or increased risk of coronary artery disease and/or those receiving cardiotoxic chemotherapy.
- Use with caution in patients at risk of bleeding, including those receiving concomitant antiplatelets and/or anticoagulants.
- Ramucirumab has not been evaluated in patients with serious or non-healing wounds and may impair healing. Withhold prior to surgery until the wound has fully healed.
- Use with caution in patients with risk factors for GI perforation, including intra-abdominal metastases, inflammatory bowel disease, diverticulitis, ischemic bowel, peptic ulcers, obstruction and injury from endoscopy and surgery.
Pregnancy/Lactation:
- Ramucirumab is not recommended for use in pregnancy. Adequate contraception should be used by both sexes during treatment and at least for 3 months after the last dose.
- Breastfeeding is not recommended during treatment and for at least 3 months after the last dose.
- Fertility effects: Probable
Female fertility may be compromised based on animal studies.
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
-
Blood pressure; Baseline and every 2 weeks, or more frequently as clinically indicated
-
CBC; Baseline and before each dose
-
Liver function tests; Baseline and before each dose
-
Thyroid function tests; Baseline and every 2 to 3 cycles. Continue after treatment as indicated (thyroid dysfunction may persist).
-
Urinalysis (for protein); Baseline and before each cycle; if urine protein level is 2+ or higher, perform 24-hour urine collection (see dose modifications table under proteinuria)
-
Clinical toxicity assessment for infusion-related reactions, bleeding, infection, thromboembolism, cardiotoxicity, GI and neurologic effects, and impaired wound healing; At each visit
-
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
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Fuchs CS, Tomasek J, Yong CJ, et al; REGARD Trial Investigators. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma
(REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014 Jan 4;383(9911):31-9.
Ramucirumab drug monograph, Ontario Health (Cancer Care Ontario).
March 2023 Modified Dosage with toxicity and Adverse effects sections
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.
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