Complete remission, which means all enlarged lymph nodes return to normal size and any symptoms subside, can happen quickly after starting chemotherapy and last four to 10 months or longer. After diagnosis, staging tests are important, because they can help dog owners gain a better understanding of the long-term outcomes. For example, T-cell immunophenotype and higher stage at diagnosis often means less response to treatment and shorter remission. Unfortunately, lymphoma is rarely cured and almost always relapses and becomes resistant to treatment.¹

Here's what you need to know about chemotherapy protocols for lymphoma in dogs, including common treatments and side effects.

Induction or First-Line Chemotherapy

CHOP-based chemotherapy (Cyclophosphamide, Hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], and Prednisone) is often considered the best induction protocol for dogs with lymphoma.¹ CHOP results in remission in more than 80% of dogs with B-cell lymphoma that lasts eight months or longer.⁴ CHOP is usually 19 or 25 weeks and consists of four cycles for a total of 16 treatments.⁵ The 25-week protocol includes a week off between treatments starting in the third cycle, which may help owners who can't come for treatment 19 weeks in a row.

CHOP Chemotherapy Treatment Cycle
Week 1	CBC + Vincristine + Prednisone (first month only)
Week 2	CBC + Cyclophosphamide + Prednisone + Furosemide
Week 3	CBC + Vincristine + Prednisone
Week 4	CBC + Doxorubicin + Prednisone
Week 5	CBC to check neutrophils

Other induction options include doxorubicin¹ (the most effective CHOP drug), and rabacfosadine (Tanovea; the only fully FDA-approved treatment for canine lymphoma).⁶ While not as effective as CHOP, these options still frequently result in complete remission lasting six months or more. Doxorubicin and Tanovea are administered every three weeks for five total treatments, which makes them good alternatives for owners who can't make frequent visits or afford more intense protocols.

Re-Induction and Rescue Chemotherapy

CHOP can be restarted when lymphoma recurs or relapses, but the second remission is usually shorter than the first. Mitoxantrone can be substituted for doxorubicin after the fifth or sixth dose of doxorubicin to reduce the risk of cardiotoxicity. The next relapse triggers rescue chemotherapy—protocols initiated when first-line protocols stop working. Rescue chemotherapy options include Tanovea, LAP (Lomustine, L-asparaginase, and Prednisone)⁷, MOPP (Mechlorethamine, Vincristine [Oncovin], Procarbazine, and Prednisone)⁸, LOPP (Lomustine, Vincristine [Oncovin], Procarbazine, and Prednisone)⁹, DMAC (Dexamethasone, Melphalan, Actinomycin-D, and Cytosine Arabinoside)¹⁰, dacarbazine¹¹, temozolomide¹², and vinblastine¹³.

Since rescue protocols are used against more resistant cancer, they don't result in remission as frequently or for as long as first-line treatments. They also often have increased risks of side effects. If a dog is feeling well, a rescue protocol may be continued as long as the lymphoma isn't progressing. Rescue protocols may only work for weeks to months before needing to switch to a different method.

Treatment-Related Adverse Events or Side Effects

Before starting chemotherapy, talk to owners about potential side effects and explain that most dogs and cats tolerate chemotherapy well. Lymphoma doesn't usually cause pain, so pain medications aren't typically needed. Common side effects can be remembered as BAG side effects: bone marrow, alopecia, and gastrointestinal (GI) side effects. Encourage owners to reach out if they're concerned about any potential chemotherapy side effects or changes they see at home.

Bone Marrow

During chemotherapy protocols, decreases in neutrophils (white blood cells) can lead to infections and/or sepsis.

• Check a CBC before treatment to make sure the pet has enough neutrophils (usually >1,500–2,500/µl).
• Check a CBC a week later to identify the nadir or low point.
• If the neutrophil count drops to <1,000/µl at the nadir, antibiotics and lowering the chemotherapy dose may be needed.
• Dogs with counts <1,000/µl that don't have a fever and feel well can get antibiotics at home.
• Dogs with counts <1,000/µl that have a fever or feel sick should be hospitalized for fluids and antibiotics.

Neutrophils usually rebound to >1,000/µl after two to three days in most cases. Advise owners to keep an eye out for decreased energy or fever about a week after treatment, which may be a sign of decreased neutrophils. Some owners can even be shown how to check their dog's temperature at home.

Alopecia

Owners may be concerned about alopecia, since people undergoing chemotherapy often lose their hair, but this is rare in dogs. Alopecia can be seen in breeds with constantly growing hair coats, such as poodles. Shaved fur may take longer than normal to regrow, so it's recommended to limit shaving as much as possible.

GI Side Effects

GI side effects usually happen three to five days after treatment. These side effects may include:

• Decreased appetite
• Nausea
• Vomiting
• Diarrhea

Most GI upset resolves without treatment beyond withholding food for 24 hours or using a bland diet. It's also a good idea to avoid most prophylactic medications for stomach upset, other than prescribing a course of maropitant (Cerenia) or ondansetron to have at home in case of vomiting. Other medications should only be prescribed if needed to avoid unnecessary costs.

Probiotics can be used for diarrhea, and appetite stimulants, like capromorelin (Entyce), can be used for dogs that lose their appetites. Most dogs can continue on their normal food, since frequent changes can cause stomach upset. If stomach upset happens and can't be controlled with medications, the chemotherapy doses can be decreased.

Other Common Side Effects

Additional side effects associated with customary chemotherapy drugs include:

Drug	Side Effects	Treatment/Prevention
Cyclophosphamide	Sterile hemorrhagic cystitis	Increase urine output with diuretics (e.g., furosemide) Provide fresh water at all times Let the dog out to urinate frequently for 24–72 hours
Doxorubicin	Vesicant (causes severe injury if it leaks outside a vein), cumulative dose-related cardiotoxicity, hypersensitivity reactions	Give over 20 to 30 minutes through a one-stick IV catheter Screen for cardiac abnormalities with ECG or echocardiogram Limit total lifetime dose
L-asparaginase	Pancreatitis, hypersensitivity reactions (increasing risk with multiple treatments)	Give diphenhydramine
Lomustine	Hepatotoxicity	Give Denamarin14
Rabacfosadine	Dermatitis, otitis externa, pulmonary fibrosis	Stop treatment and reduce the dose Give prednisone to reduce the risk of pulmonary fibrosis Avoid in West Highland White Terriers due to breed predisposition for pulmonary fibrosis
Vincristine	Vesicant, paralytic ileus, peripheral neuropathy	Give through a one-stick IV catheter Treat ileus with prokinetics (e.g., metoclopramide)

Working with Pet Owners

Lymphoma is an aggressive cancer that responds well to chemotherapy, and several chemotherapy options are available. Chemotherapy is generally well-tolerated, but veterinarians and pet owners should be aware of possible side effects, including when they might happen and how they can be managed. Maintain communication with pet owners and encourage questions to help them understand their pet's treatment.

Veterinarians can work with pet owners to find the right chemotherapy protocol for each dog with lymphoma, taking into consideration cost, time commitment, potential side effects, and efficacy to maximize quality of life for the pet and their family.

References

1. Vail DM, Pinkerton M, and Young KM. "Hematopoietic Neoplasia." Withrow and MacEwen's Small Animal Clinical Oncology 6th Edition. Elsevier, 2019, pp 688-772.
2. Best MP, et al. "Long-term remission and survival in dogs with high-grade, B cell lymphoma treated with chemotherapy with or without sequential low-dose rate half-body irradiation." J Vet Intern Med, 2023; 37(6):2368–2374. doi: 10.1111/jvim.16840.
3. Gareau A, Sekiguchi T, Warry E, Ripoll AZ, Sullivan E, Westfall T, Chretin J, Fulton LM, Harkey M, Storb R, Suter SE. "Allogeneic peripheral blood haematopoietic stem cell transplantation for the treatment of dogs with high-grade B-cell lymphoma." Vet Comp Oncol, 2022; 20(4):862–870. doi: 10.1111/vco.12847.
4. Childress MO, Ramos-Vara JA, Ruple A. "Retrospective analysis of factors affecting clinical outcome following CHOP-based chemotherapy in dogs with primary nodal diffuse large B-cell lymphoma." Vet Comp Oncol, 2018; 16(1):E159–E168. doi: 10.1111/vco.12364.
5. Hawkes C, Morris J, Bavcar S, Wilkie C, Ray S, Auquier C, Benjamin S, Massó JB, Bottin S, Davies O, Desmas-Bazelle I, Einhorn A, Figueroa-Gonzalez C, Holenova K, Kritsotalaki E, Peak K, Smallwood K, Treggiari E, Valenti P, de la Virgen MG, Fournier Q. "Comparison of CHOP-19 and CHOP-25 for treatment of peripheral nodal B-cell lymphoma in dogs: A European multicenter retrospective cohort study." J Vet Intern Med, 2024; 38(6):3193–3205. doi: 10.1111/jvim.17222.
6. Weishaar KM, Wright ZM, Rosenberg MP, Post GS, McDaniel JA, Clifford CA, Phillips BS, Bergman PJ, Randall EK, Avery AC, Thamm DH, Christman Hull AA, Gust CM, Donoghue AR. "Multicenter, randomized, double-blinded, placebo-controlled study of rabacfosadine in dogs with lymphoma." J Vet Intern Med, 2021; 36(1):215–226. doi: 10.1111/jvim.16341.
7. Saba CF, Hafeman SD, Vail DM, Thamm DH. "Combination chemotherapy with continuous L-asparaginase, lomustine, and prednisone for relapsed canine lymphoma." J Vet Intern Med, 2009; 23(5):1058–63. doi: 10.1111/j.1939-1676.2009.0357.x.
8. Rassnick KM, Mauldin GE, Al-Sarraf R, Mauldin GN, Moore AS, Mooney SC. "MOPP chemotherapy for treatment of resistant lymphoma in dogs: a retrospective study of 117 cases (1989-2000)." J Vet Intern Med, 2002; 16(5):576–80. doi: 10.1892/0891-6640(2002)016<0576:mcftor>2.3.co;2.
9. Fahey CE, Milner RJ, Barabas K, Lurie D, Kow K, Parfitt S, Lyles S, Clemente M. "Evaluation of the University of Florida lomustine, vincristine, procarbazine, and prednisone chemotherapy protocol for the treatment of relapsed lymphoma in dogs: 33 cases (2003-2009)." J Am Vet Med Assoc, 2011; 239(2):209–15. doi: 10.2460/javma.239.2.209.
10. Alvarez FJ, Kisseberth WC, Gallant SL, Couto CG. "Dexamethasone, melphalan, actinomycin D, cytosine arabinoside (DMAC) protocol for dogs with relapsed lymphoma." J Vet Intern Med, 2006; 20(5):1178–83. doi: 10.1892/0891-6640(2006)20[1178:dmadca]2.0.co;2.
11. Griessmayr PC, Payne SE, Winter JE, Barber LG, Shofer FS. "Dacarbazine as single-agent therapy for relapsed lymphoma in dogs." J Vet Intern Med, 2009; 23(6):1227–31. doi: 10.1111/j.1939-1676.2009.0376.x.
12. Dervisis NG, Dominguez PA, Sarbu L, Newman RG, Cadile CD, Swanson CN, Kitchell BE. "Efficacy of temozolomide or dacarbazine in combination with an anthracycline for rescue chemotherapy in dogs with lymphoma." J Am Vet Med Assoc, 2007; 231(4):563–9. doi: 10.2460/javma.231.4.563.
13. Lenz JA, Robat CS, Stein TJ. "Vinblastine as a second rescue for the treatment of canine multicentric lymphoma in 39 cases (2005 to 2014)." J Small Anim Pract, 2016; 57(8):429–34. doi: 10.1111/jsap.12500.
14. Skorupski KA, Hammond GM, Irish AM, Kent MS, Guerrero TA, Rodriguez CO, Griffin DW. "Prospective randomized clinical trial assessing the efficacy of Denamarin for prevention of CCNU-induced hepatopathy in tumor-bearing dogs." J Vet Intern Med, 2011; 25(4):838–45. doi:10.1111/j.1939-1676.2011.0743.x.

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