Should I treat dogs with T cell lymphoma with a different chemotherapy protocol than for B cell?

T-cell multicentric lymphomas in dogs present a challenge for clinicians. These aggressive malignancies usually have a significantly poorer prognosis compared to B-cell lymphomas, prompting the need for more effective treatment approaches. Chemotherapy protocols that are feature heavily in drugs from a class known as “alkylating agents” in have emerged as a promising strategy in treating this disease.

Alkylating agents, such as cyclophosphamide, lomustine (CCNU), chlorambucil and melphalan, work by inducing DNA damage that prevents cancer cells from replicating. This mechanism is particularly effective against rapidly dividing cells, such as those found in aggressive T-cell lymphomas. In dogs, alkylator-rich protocols like LOPP regimens have demonstrated potential, with some studies indicating that this approach can lead to improved survival times in dogs with T-cell lymphoma. One study of 35 dogs with T cell lymphoma found that dogs treated with the LOPP protocol, consisting of lomustine, vincristine, procarbazine and prednisolone had a median progression-free survival (PFS) of 431 days and a median survival time (MST) of 507 days (1).  This suggests a significant improvement compared to traditional CHOP protocols (cyclophosphamide, doxorubicin, vincristine, prednisolone), with one study reporting a MST of only 235 days for dogs treated with this protocol (2).

However, the story is different in human medicine, particularly for patients with the equivalent of multicentric T cell lymphoma, which goes by the somewhat prosaic name of peripheral T cell lymphoma not otherwise specified (PTCL-NOS).  Just like in dogs, PTCL-NOS is an aggressive and challenging lymphoma subtype with a poor prognosis, and yet the standard of care approach with people with this disease remains CHOP-based regimens.

There are a few reasons why this may be the case.

1. Lack of Superior Efficacy: Despite their potency, alkylator-rich regimens have not consistently shown superior outcomes in PTCL-NOS compared to CHOP- based regimens (3)

2. Toxicity Concerns: Alkylating agents, especially when used in high doses, are associated with significant toxicity, including severe myelosuppression, organ damage, and an increased risk of secondary cancers. Whilst this is a greater concern in human medicine compared with veterinary due to the much higher dose rates employed, this has resulted in caution in their use.

3. Emergence of Targeted Therapies: The development of targeted therapies and immunomodulatory drugs has shifted the focus away from treatment regimens purely based on traditional chemotherapy in people, reducing the need for more toxic alkylating agents.

 While alkylator-rich protocols such as LOPP demonstrate potential for treating T-cell lymphoma in dogs, caution must be exercised when interpreting results from retrospective studies that use historical controls. These studies, while informative, are limited by biases such as differences in patient populations and the lack of randomisation. Without the rigour of well-designed prospective, randomised controlled trials, conclusions drawn from these studies may not fully capture the effectiveness of LOPP compared to other treatments like CHOP. Until such data are available, the choice of protocol remains heavily dependent on the clinician's experience and judgment.

1.     Morgan E, O'Connell K, Thomson M, Griffin A. Canine T cell lymphoma treated with lomustine, vincristine, procarbazine, and prednisolone chemotherapy in 35 dogs. Vet Comp Oncol. 2018 Dec;16(4):622-629.

2.     Rebhun RB, Kent MS, Borrofka SA, Frazier S, Skorupski K, Rodriguez CO. CHOP chemotherapy for the treatment of canine multicentric T-cell lymphoma. Vet Comp Oncol. 2011 Mar;9(1):38-44. 

3.     Dreger, P., Corradini, P., Kimby, E., Kolstad, A., André, M., & Corradini, P. (2012). Conditioning and allogeneic hematopoietic stem cell transplantation for peripheral T-cell lymphoma: A consensus paper by the European Society for Blood and Marrow Transplantation (EBMT) and the European Society for Medical Oncology (ESMO). Bone Marrow Transplantation, 47(3), 309-317. 

Five canine malignancies that respond to chemotherapy

Cancer is a notoriously difficult group of diseases to treat and it is often difficult to be able to advise pet owners if it is worth their while to start medical therapy (i.e., chemotherapy). Here are five common cancer types for which there is good evidence that chemotherapy makes a difference in survival outcomes.

1. Lymphoma: Lymphoma is one of the most common malignancies in dogs and is highly responsive to chemotherapy. Untreated, the median survival time is 4-6 weeks. The standard of care treatment regimen involves multi-agent chemotherapy protocols, such as CHOP (Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone). Dogs treated with chemotherapy often achieve complete remission, with a median survival time (MST) ranging from 10 to 14 months. Approximately 80-90% of dogs will achieve remission with CHOP, making it a cornerstone in lymphoma treatment (1).

 2. Mast Cell Tumours: Mast cell tumours (MCTs) are the most common cutaneous tumours in dogs. High-grade MCTs or those that cannot be completely excised surgically are typically treated with chemotherapy, with toceranib (Palladia), vinblastine and lomustine (CCNU) most frequently used. A combination of surgery and chemotherapy can significantly improve outcomes, particularly in high-grade cases, with a MST of around 11 months and extending beyond two years for some dogs (2). Untreated, dogs with high grade MCTs have a MST of 4-5 months (3).

 3. Osteosarcoma: While surgery (amputation or limb-sparing techniques) is the primary treatment for osteosarcoma, chemotherapy is critical in managing metastatic disease, which is all but expected in this aggressive malignancy. The most commonly used chemotherapeutic agent is carboplatin. Dogs treated with both surgery and chemotherapy have a MST of 10-12 months (4), compared to 4-6 months with surgery alone (5).

 4. Haemangiosarcoma: Haemangiosarcoma is a highly malignant cancer of the blood vessels, often affecting the spleen. Surgery is typically the first step, but chemotherapy is essential due to the high likelihood of metastasis. Doxorubicin is the drug of choice, and while the prognosis is guarded, chemotherapy can extend survival by a number of months (6).

 5. Transitional Cell Carcinoma: Transitional cell carcinoma, now more frequently referred to as urothelial carcinoma, primarily affects the bladder, is another malignancy that benefits from chemotherapy, especially when surgical options are limited. Mitoxantrone, vinblastine and piroxicam are often used, with some dogs experiencing prolonged survival in excess of 12 months. Chemotherapy helps in reducing tumour size, alleviating symptoms, and improving quality of life (8).

 Whilst chemotherapy is not always curative, it can significantly prolong survival in many cases, with life quality preserved in the hands of a sensitive clinician. By understanding the potential benefits and carefully tailoring treatments, veterinarians can make a meaningful difference to their cancer patients.

1.     Garrett LD, Thamm DH, Chun R, Dudley R, Vail DM. Evaluation of a 6-month chemotherapy protocol with no maintenance therapy for dogs with lymphoma. J Vet Intern Med. 2002 Nov-Dec;16(6):704-9.

2.     Cooper M, Tsai X, Bennett P. Combination CCNU and vinblastine chemotherapy for canine mast cell tumours: 57 cases. Vet Comp Oncol. 2009 Sep;7(3):196-206. 

3.     Burge R, Woolard KD, Willcox JL, Rebhun RB, Burton JH, Al-Nadaf S, Skorupski KA. High-Grade, Stage 2 Mast Cell Tumors: Outcome in Dogs With Local and Systemic Therapy. J Am Anim Hosp Assoc. 2023 Jul 1;59(4):167-176. 

4.     Skorupski KA, Uhl JM, Szivek A, Allstadt Frazier SD, Rebhun RB, Rodriguez CO Jr. Carboplatin versus alternating carboplatin and doxorubicin for the adjuvant treatment of canine appendicular osteosarcoma: a randomized, phase III trial. Vet Comp Oncol. 2016 Mar;14(1):81-7. 

5.     Straw RC, Withrow SJ, Richter SL, Powers BE, Klein MK, Postorino NC, LaRue SM, Ogilvie GK, Vail DM, Morrison WB, et al. Amputation and cisplatin for treatment of canine osteosarcoma. J Vet Intern Med. 1991 Jul-Aug;5(4):205-10. 

6.     Sorenmo KU, Baez JL, Clifford CA, Mauldin E, Overley B, Skorupski K, Bachman R, Samluk M, Shofer F. Efficacy and toxicity of a dose-intensified doxorubicin protocol in canine hemangiosarcoma. J Vet Intern Med. 2004 Mar-Apr;18(2):209-13. 

7.     Arnold EJ, Childress MO, Fourez LM, Tan KM, Stewart JC, Bonney PL, Knapp DW. Clinical trial of vinblastine in dogs with transitional cell carcinoma of the urinary bladder. J Vet Intern Med. 2011 Nov-Dec;25(6):1385-90.