CHOP / CEOP Chemotherapy Protocol
Cyclophosphamide, Doxorubicin (or Epirubicin), Vincristine, Prednisolone
Also known as: CHOP Protocol · CEOP Protocol · Madison-Wisconsin Protocol · UW-25 Protocol · L-CHOP
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Lymphoma (CHOP/CEOP Protocol - Vincristine) | 0.7 mg/m2 | IV | once | Weeks 1, 3, 6, 8, 11, 15, 19, 23 | 🌍 EU |
| Lymphoma (CHOP/CEOP Protocol - Prednisolone) | 2 mg/kg (Wk 1); 1.5 mg/kg (Wk 2); 1 mg/kg (Wk 3); 0.5 mg/kg (Wk 4) | PO | q24h | First 4 weeks only, then stopped | 🌍 EU |
| Lymphoma (CHOP/CEOP Protocol - Cyclophosphamide) | 250 mg/m2 | PO/IV | once | Weeks 2, 7, 13, 21 | 🌍 EU |
| Lymphoma (CHOP/CEOP Protocol - Furosemide) | 1 mg/kg | PO | q12h | For 48h (4 doses) concurrent with cyclophosphamide | 🌍 EU |
| Lymphoma (CHOP/CEOP Protocol - Doxorubicin or Epirubicin) | 30 mg/m2 (Use 1 mg/kg for patients <15 kg) | IV | once | Weeks 4, 9, 17, 25 | 🌍 EU |
| Lymphoma (CHOP/CEOP Protocol - Maropitant) | 1 mg/kg | SC | once | Prior to doxorubicin/epirubicin | 🌍 EU |
| Lymphoma (CHOP/CEOP Protocol - Omeprazole) | 1 mg/kg | PO | q12h or q24h | First 21 days | 🌍 EU |
| Lymphoma (Alternative to Cyclophosphamide - Chlorambucil) | 20 mg/m2 | PO | once | As needed | 🌍 EU |
| Lymphoma (Alternative to Doxorubicin - Mitoxantrone) | 5.5 mg/m2 | IV | once | As needed | 🌍 EU |
- Lymphoma (CHOP/CEOP Protocol - Vincristine): Strict first-stick IV catheter only. Vesicant.
- Lymphoma (CHOP/CEOP Protocol - Prednisolone): Tapering dose.
- Lymphoma (CHOP/CEOP Protocol - Cyclophosphamide): Administer with Furosemide.
- Lymphoma (CHOP/CEOP Protocol - Furosemide): To prevent haemorrhagic cystitis.
- Lymphoma (CHOP/CEOP Protocol - Doxorubicin or Epirubicin): Give in 0.9% NaCl (not Hartmann's) over 20 minutes. Vesicant.
- Lymphoma (CHOP/CEOP Protocol - Maropitant): Anti-emetic premedication.
- Lymphoma (CHOP/CEOP Protocol - Omeprazole): GI protectant. Ranitidine with sucralfate is an alternative.
- Lymphoma (Alternative to Cyclophosphamide - Chlorambucil): Used if haemorrhagic cystitis develops.
- Lymphoma (Alternative to Doxorubicin - Mitoxantrone): Given over 10 minutes. Used in cases of cardiac dysfunction.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
The 25-week CHOP/CEOP protocol is a standard multi-agent chemotherapy regimen used primarily for the treatment of intermediate to high-grade lymphoma in dogs. It utilizes a rotating schedule of drugs with different mechanisms of action to maximize tumor cell kill while minimizing overlapping toxicities.
Critical Warning: Vincristine and Doxorubicin/Epirubicin are severe vesicants. Intravenous catheters must be placed in all cases, and ONLY catheters placed by a clean 'first-stick' should be used. If extravasation occurs, contact an oncologist immediately.
Clinical Pearl: Furosemide is co-administered with cyclophosphamide to induce diuresis, significantly reducing the contact time of toxic metabolites (acrolein) with the bladder mucosa, thereby minimizing the risk of sterile haemorrhagic cystitis.
Mechanism of action
This protocol relies on the synergistic action of four distinct drug classes:
- Cyclophosphamide: Alkylating agent → cross-links DNA strands, preventing replication.
- Doxorubicin/Epirubicin: Anthracycline antibiotic → inhibits topoisomerase II, intercalates DNA, and generates free radicals.
- Vincristine: Vinca alkaloid → binds to tubulin, inhibiting microtubule formation and arresting cells in metaphase.
- Prednisolone: Glucocorticoid → induces apoptosis in lymphoid cells.
Safety & warnings
Contraindications
- Severe myelosuppression (neutrophil count < 3 x 10^9/l)
- Pre-existing severe cardiac dysfunction (relative contraindication for doxorubicin; use mitoxantrone instead)
- Active haemorrhagic cystitis (substitute cyclophosphamide with chlorambucil)
- MDR1 mutation (requires significant dose reduction or avoidance of vincristine and doxorubicin)
Adverse effects
- Myelosuppression (neutropenia, thrombocytopenia)
- Gastrointestinal toxicity (vomiting, diarrhea, anorexia)
- Haemorrhagic cystitis (specific to cyclophosphamide)
- Severe tissue necrosis if extravasated (vincristine, doxorubicin)
- Cardiotoxicity (specific to doxorubicin)
- Alopecia (breed dependent)
Precautions
Myelosuppression Management:
- If neutrophils >3 x 10^9/l and platelets >100 x 10^9/l: Proceed with treatment.
- If neutrophils <3 x 10^9/l: Suspend treatment, recheck in 5-7 days.
- If neutrophils <1 x 10^9/l: Prescribe prophylactic antibiotics. Decrease next dose of the responsible chemotherapy drug by 10%.
- If neutrophils <1 x 10^9/l AND patient is pyrexic/unwell: Administer IV antibiotics and contact an oncologist.
MDR1 Breeds: Collie-type breeds are highly sensitive to vincristine and doxorubicin due to the MDR1 (ABCB1) mutation. Commercial testing is strongly recommended prior to initiating therapy.
Drug interactions
Alters hepatic cytochrome P450 enzyme pathway, potentially altering the metabolism and increasing toxicity of chemotherapeutics.
Monitoring
- Haematology prior to each treatment
- Nadir neutrophil count 7 days after the first doxorubicin treatment
- Free-catch urine dipstick prior to each cyclophosphamide administration (check for blood)
- Urine culture if blood is noted on dipstick
- Biochemistry prior to first treatment and minimum every 6 months
- Baseline echocardiography (especially before doxorubicin if pre-existing heart disease is suspected)
Pharmacokinetics
Half-life
Absorption
Varies by drug. Cyclophosphamide and prednisolone are well absorbed orally.
Distribution
Wide distribution. Doxorubicin concentrates in tissues. Vincristine binds heavily to blood elements.
Metabolism
Hepatic. Cyclophosphamide requires hepatic activation to its active alkylating metabolites. Doxorubicin and vincristine undergo extensive hepatic metabolism (CYP450).
Elimination
Vincristine and doxorubicin are primarily excreted in feces via the biliary system. Cyclophosphamide metabolites are excreted in urine.
Overdose
Overdosage of any component of the CHOP protocol can lead to life-threatening myelosuppression (profound neutropenia and sepsis), severe gastrointestinal mucosal sloughing, and acute cardiotoxicity (doxorubicin). Treatment is strictly supportive, including broad-spectrum IV antibiotics, aggressive fluid therapy, anti-emetics, and potentially granulocyte colony-stimulating factor (G-CSF).
Available products
Formulations
- Vincristine: Injectable solution
- Cyclophosphamide: Oral tablets, Injectable solution
- Doxorubicin/Epirubicin: Injectable solution
- Prednisolone: Oral tablets
Veterinary
- Various generic formulations available depending on the specific drug
Human-labeled
- Oncovin (Vincristine)
- Endoxana (Cyclophosphamide)
- Adriamycin (Doxorubicin)
Regulatory status
Standard of care for canine lymphoma.
Handled under strict hazardous drug protocols.
Handled under strict hazardous drug protocols.
No regulatory data for: 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Vincristine and Doxorubicin injectables must be refrigerated and protected from light. Cyclophosphamide tablets should be stored at room temperature. Follow specific manufacturer guidelines for each agent.
Client information
Your dog is undergoing a comprehensive 25-week chemotherapy protocol.
- Side Effects: Dogs generally tolerate chemotherapy much better than humans. Hair loss is rare (except in certain breeds like Poodles or Terriers), but mild stomach upset or tiredness for 1-2 days post-treatment can occur.
- Infection Risk: Because these drugs lower the white blood cell count, your dog is at a higher risk for infection. Seek immediate veterinary care if your dog develops a fever, severe lethargy, or stops eating.
- Urinary Monitoring: Watch your dog's urine closely. If you see any signs of blood or straining to urinate, contact your vet immediately, as this can be a side effect of one of the drugs (cyclophosphamide).
- Safety: Chemotherapy drugs are excreted in your pet's waste. Wear gloves when cleaning up urine, feces, or vomit for at least 48 hours after each treatment.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.