Canis ISSN: 2398-2942

Lymphoma: chemotherapy protocols

Synonym(s): Lymphosarcoma: chemotherapy protocols

Contributor(s): Laura Garrett, Corey Saba

Induction protocols

Protocol 1: Modified UW-Madison (UW 25) (CHOP-based)

Print table for completion by veterinarian Chemotherapy protocol: Modified UW-Madison (UW 25).

A CBC Hematology: complete blood count (CBC) must be performed within 48 hours prior to chemotherapy administration.

Induction

Week 1:

Week 2:

  • Cyclophosphamide Cyclophosphamide : 250 mg/m2 IV or PO.
  • Give 1 dose of oralLasix@ 2 mg/kg.
  • Prednisone: 1.5 mg/kg PO SID.

Week 3:

  • Vincristine: 0.5-0.7 mg/m2 IV.
  • Prednisone: 1 mg/kg PO SID.

Week 4:

  • Doxorubicin Doxorubicin : 30 mg/m2 IV.
  • Prednisone: 0.5 mg/kg PO SID.

Week 5:

  • CBC only. No chemotherapy. Discontinue prednisone.

Week 6:

  • Vincristine: 0.5-0.7 mg/m2 IV.

Week 7:

  • Cyclophosphamide Cyclophosphamide: 250 mg/m2 IV or PO.
  • Give 1 dose of oral Lasix@ 2mg/kg.

Week 8:

  • Vincristine: 0.5-0.7 mg/m2 IV.

Week 9:

  • Doxorubicin:30 mg/m2 IV.

Week 10:

  • No chemotherapy.
  • If patient is in complete remission, continue with treatments at 2 week intervals on week 11.

Maintenance

Week 11:

  • Vincristine: 0.5-0.7 mg/m2 IV.

Week 13:

  • Cyclophosphamide: 250 mg/m2 IV or PO.
  • Give 1 dose of oral Lasix@ 2mg/kg.

Week 15:

  • Vincristine:0.5-0.7 mg/m2 IV.

Week 17:

  • Doxorubicin: 30 mg/m2 IV.

Week 19:

  • Vincristine: 0.5-0.7 mg/m2 IV

Week 21:

  • Cyclophosphamide: 250 mg/m2 IV or PO.
  • Give 1 dose of oral Lasix@ 2mg/kg.

Week 23:

  • Vincristine: 0.5-0.7 mg/m2 IV.

Week 25:

  • Doxorubicin: 30 mg/m2 IV.

Important considerations

  • For dogs weighing <15 kg, consider 0.5 mg/m2 of vincristine, 200 mg/m2 of cyclophosphamide, and 1 mg/kg of doxorubicin.
  • Myelosuppression and gastrointestinal toxicity (eg inappetence, vomiting, and/or diarrhea) are possible toxicities of vincristine, cyclophosphamide, and doxorubicin.
  • Additional toxicities of vincristine include:
    • Severe tissue necrosis and extravasation injury if given outside of the vein.
    • Peripheral neuropathies, most commonly manifested as paralytic ileus.
  • An additional toxicity of cyclophosphamide includes sterile hemmorrhagic cystitis Cystitis. To reduce this risk, administer cyclophosphamide concurrently with a single dose of Lasix to promote bladder emptying. Give the medications as early in the day as possible. Provide adequate amounts of water, and allow dogs to go outside to urinate every 1-2 hours after drug administration for the duration of the day. If hemorrhagic cystitis occurs, discontinue cyclophosphamide and Lasix. Substitute in chlorambucil Chlorambucil @ 1.4 mg/kg PO.
  • Additional toxicities of doxorubicin include:
    • Severe tissue necrosis and extravasation injury if given outside of the vein. Doxorubicin should be administered through a "clean stick" catheter. Careful monitoring of the patient is advised during administration to ensure the catheter remains in place.
    • Hemorrhagic colitis Colitis: overview.
    • Anaphylactoid reactions secondary to mast cell degranulation. Pre-medication with 1-2 mg/kg of diphendydramine IM approximately 30 minutes prior to treatment is recommended by some oncologists to prevent this toxicity.
    • Acute cardiac toxicity manifested as arrhythmias.
    • Cumulative toxicity to cardiac myocytes in dogs. To avoid cumulative cardiotoxicity, maintain clear records of the total doxorubicin dose to date (in total mg, as well as total mg/m2) for each patient. Do not exceed >180 mg/m2 total cumulative dose.
    • Acute toxicities may be minimized by administering the drug slowly (over 30 minutes or at 1 mg/min if <10 mg).
  • A complete blood count (CBC) with platelet count Hematology: platelet count must be performed within 48 hours prior to chemotherapy administration. Delay chemotherapy by 3-7 days and then recheck CBC if:
    • Neutrophil count <2000 cells/µl.
    • Platelet count <75,000 cells/µl.
    • Patient is exhibiting GI signs secondary to previous chemotherapy.
  • Reduce chemotherapy dose by 25% in patients experiencing significant myelosuppression, GI toxicity and/or those requiring treatment delays during weekly administration.
  • If patient is in complete remission at week 25, discontinue all therapy and re-evaluate monthly with a thorough physical examination.

Protocol 2: Single-agent doxorubicin

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Protocol 3: Combination cytotoxic therapy COP

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Rescue protocols

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Legal and safety precautions

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Saba C F, Thamm D H, Vail D M (2007) Combination chemotherapy with L-asparginase, lomustine and prednisone for relapsed or refractory canine lymphoma. J Vet Intern Med 21 (1), 127-131 PubMed.
  • Simon D, Nolte I, Eberle N et al (2006) Treatment of dogs with lymphoma using a 12-week, maintenance-free combination chemotherapy protocol. J Vet Intern Med 20 (4), 948-954 PubMed.
  • MacDonald V S, Thamm D H, Kurzman I D et al (2005) Does L-asparaginase influence efficacy or toxicity when added to a standard CHOP protocol for dogs with lymphoma? J Vet Intern Med 19 (5), 732-736 PubMed.
  • Jeffreys A B, Knapp D W, Carlton W W et al (2005) Influence of asparaginase on a combination chemotherapy protocol for canine multicentric lymphoma. JAAHA 41 (4), 221-226 PubMed.
  • Vail D M & Thamm D H (2005) Cytotoxic chemotherapy: new players, new tacticsJAAHA 41 (4), 209-214 PubMed.
  • Kristal O, Rassnick K M, Gliatto J M et al (2004) Hepatotoxicity associated with CCNU (lomustine) chemotherapy in dogs. J Vet Intern Med 18 (1), 75-80 PubMed.
  • Brønden LB, Rutteman G R, Flagstad A et al (2003) Study of dog and cat owners' perceptions of medical treatment for cancer. Vet Rec 152 (3), 77-80 PubMed.
  • Charney S C, Bergman P J, Hohenhaus A E et al (2003) Risk factors for sterile hemorrhagic cystitis in dogs with lymphoma receiving cyclophosphamide with or without concurrent administration of furosemide: 216 cases (1990-1996). JAVMA 222 (10), 1388-1393 PubMed.
  • Garrett L D, Thamm D H, Chun R et al (2002) Evaluation of a 6-month chemotherapy protocol with no maintenance therapy for dogs with lymphoma. J Vet Intern Med 16 (6), 704-709 PubMed.
  • Rassnick K M, Mauldin G E, Al-Sarraf R et al (2002) MOPP chemotherapy for treatment of resistant lymphoma in dogs: a retrospective study of 117 cases (1989-2000). JVIM 16 (5), 576-580 PubMed.
  • Moore A S, Cotter S M, Rand W M et al (2001) Evaluation of a continuous treatment protocol (VELCAP-S) for canine lymphoma. J Vet Intern Med 15 (4), 348-354 PubMed.
  • Boyce K L & Kitchell B E (2000) Treatment of canine lymphoma with COPLA/LVP. JAAHA 36 (5), 395-403 PubMed.
  • Chun R, Garrett L D & Vail D M (2000) Evaluation of a high-dose chemotherapy protocol with no maintenance therapy for dogs with lymphoma. J Vet Intern Med 14 (2), 120-124 PubMed.
  • Piek C J, Rutteman G R & Teske E (1999) Evaluation of the results of a L-asparaginase-based continuous chemotherapy protocol versus a short doxorubicin-based induction chemotherapy protocol in dogs with malignant lymphoma. Vet Q 21 (2), 44-49 PubMed.
  • Myers N C 3rd, Moore A S, Rand W M et al (1997) Evaluation of a multi-drug chemotherapy protocol (ACOPA 11) in dogs with lymphoma. J Vet Intern Med 11 (6), 333-339 PubMed.
  • Valerius K D, Oglivie G K, Mallinckrodt C H et al (1997) Doxorubicin alone or in combination with asparaginase, followed by cyclophosphamide, vincristine, and prednisone for treatment of multicentric lymphoma in dogs: 121 cases (1987-1995). JAVMA 210 (4), 512-516 PubMed.

Other sources of information

  • Tennant B (2002) BSAVA Small Animal Formulary, 4th edn. pp 280-281.


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