Cyramza is a brand which contains Ramucirumab. Ramucirumab is a fully human monoclonal antibody that acts as a vascular endothelial growth factor receptor-2 (VEGFR-2) antagonist. It is primarily used in the treatment of advanced or metastatic cancers, particularly gastric cancer, colorectal cancer, and non-small cell lung cancer (NSCLC). Ramucirumab works by blocking the VEGF pathway, which plays a crucial role in tumor growth and angiogenesis (the formation of new blood vessels that feed tumors) and is FDA-approved for several indications, often in combination with chemotherapy.

Mechanism of Action

Ramucirumab works by specifically binding to VEGFR-2, preventing its activation by vascular endothelial growth factors (VEGF). This inhibition leads to:

• Reduced blood supply to tumors, limiting their growth.
• Suppressed angiogenesis, which prevents the formation of new blood vessels needed by the tumor to grow.
• Inhibition of tumor progression by disrupting the VEGF signaling pathway.

Since tumors rely heavily on angiogenesis, blocking VEGFR-2 is an effective strategy to slow or stop tumor progression.

Approved Indications (Uses of Ramucirumab)

1. Gastric Cancer & Gastroesophageal Junction Adenocarcinoma

Monotherapy or in combination with paclitaxel for patients with advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma who have disease progression after prior fluoropyrimidine- or platinum-containing chemotherapy.

2. Non-Small Cell Lung Cancer (NSCLC)

Used with docetaxel for patients with metastatic NSCLC who have progressed after platinum-based chemotherapy. Suitable for patients regardless of EGFR or ALK mutation status.

3. Colorectal Cancer (mCRC - Metastatic Colorectal Cancer)

Used with FOLFIRI (fluorouracil, leucovorin, and irinotecan) for patients with metastatic colorectal cancer after disease progression on first-line therapy (bevacizumab, oxaliplatin, and fluoropyrimidine).

4. Hepatocellular Carcinoma (HCC - Liver Cancer)

Approved for patients with advanced hepatocellular carcinoma (HCC) and high alpha-fetoprotein (AFP ≥ 400 ng/mL) who have previously received sorafenib.

Ramucirumab is a highly effective VEGFR-2 inhibitor used for advanced gastric, lung, colorectal, and liver cancers. It prolongs survival when combined with chemotherapy. However, it requires careful monitoring for side effects like hypertension, bleeding, and wound healing issues.

Dosage and Administration

General Dosage Guidelines

Administered via intravenous (IV) infusion over 60 minutes.
Pre-medication with antihistamines is recommended to prevent infusion-related reactions.

Clinical Efficacy

Ramucirumab has demonstrated improved survival outcomes in clinical trials:

1. Gastric Cancer (REGARD & RAINBOW Trials)

• REGARD Trial: Median overall survival (OS) increased to 5.2 months vs. 3.8 months (placebo).

• RAINBOW Trial: Combination with paclitaxel improved OS to 9.6 months vs. 7.4 months (paclitaxel alone).

2. NSCLC (REVEL Trial)

• Combination with docetaxel extended OS to 10.5 months vs. 9.1 months (docetaxel alone).

3. Colorectal Cancer (RAISE Trial)

• Combination with FOLFIRI improved OS to 13.3 months vs. 11.7 months (placebo + FOLFIRI).

4. Hepatocellular Carcinoma (REACH-2 Trial)

• Patients with high AFP showed improved OS to 8.5 months vs. 7.3 months (placebo).

Side Effects of Ramucirumab

Common Side Effects

• Fatigue
• Hypertension (high blood pressure)
• Diarrhea
• Peripheral edema (swelling in hands/feet)
• Proteinuria (protein in urine)

Serious Side Effects

• Gastrointestinal Perforation – A rare but serious risk where a hole forms in the stomach or intestines.
• Hemorrhage (bleeding risks) – Increased risk of serious bleeding events, including gastrointestinal bleeding.
• Hypertension – Can become severe and requires regular blood pressure monitoring.
• Infusion Reactions – Rare but can include chills, fever, breathing difficulties.
• Wound Healing Delays – Patients undergoing surgery should stop Ramucirumab at least 28 days before surgery.

Contraindications and Precautions

Who Should NOT Take Ramucirumab?

• Patients with recent bleeding disorders or active hemorrhage.
• Patients undergoing major surgery soon (due to delayed wound healing).
• Pregnant women (can harm the fetus).
• Patients with uncontrolled high blood pressure (risk of hypertensive crisis).

Drug Interactions

• Antihypertensive Drugs: Blood pressure should be monitored closely if taking ACE inhibitors or beta-blockers.
• Anticoagulants (Warfarin, Heparin): Increased risk of bleeding.
• NSAIDs (Aspirin, Ibuprofen): Can increase the risk of gastrointestinal bleeding.

Pharmacokinetics

• Half-life: ~14 days
• Metabolism: Degraded by proteolytic enzymes
• Excretion: Not eliminated by kidneys or liver, making it suitable for patients with renal or hepatic impairment.