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remission is complete disappearance of all detectable lymphoma and resolution of clinical signs. Lymphoma is typically rewarding to treat with high response rates, and most dogs tolerate chemotherapy quite well.
Treatment: Chemotherapy The goal of therapy is to achieve a complete remission and a good to excellent quality of life. Dogs that respond and achieve CR are usually free of clinical signs of lymphoma and live longer and live well. Only a minority develops significant toxicity or do not respond to therapy. Most patients are treated on an outpatient basis. Newly diagnosed lymphoma patients that are sick (substage b), dehydrated, and have a large tumor burden (advanced stages) are at increased risk for acute tumor lysis syndrome with induction chemotherapy. In such cases, the dogs should be admitted for IV fluid therapy, supportive care, and intensive monitoring prior to chemo and for 24 to 72 hours after.
Combination chemotherapy provides improved remission rates and duration in comparison to single agent protocols. Multi-agent CHOP protocols are the most successful, with complete remission rates of > 80% and remission durations of typically 6-11 months. Median survival times (MST) are 1 year when followed by rescue protocol, and 25% of dogs are long term survivors > 2 years. There are numerous CHOP protocols that vary
in drug dosages, scheduling, and dose intensity. The UW-Madison protocol is often recommended for owners choosing a combination protocol for its high complete remission rates, higher remission duration, and lower morbidity and mortality rates. Commonly used UW protocols are the 25 and 19 week protocols
Multi-agent CHOP protocols typically combine vincristine, cyclophosphamide, doxorubicin and prednisone.
Recent studies suggest the inclusion of l-aspariginase at induction does not significantly impact remission duration or survival times and can be omitted and saved for the rescue protocol.
Additionally recent studies suggest there is no survival benefit of maintenance phase. Most current protocols are discontinuous without a chronic maintenance phase and provide comparable remission durations. It is thought
the period without chemotherapy may lead to greater responsiveness at relapse by lack of selection of resistant cells.
For some clients, alternative protocols are elected over the multi-agent CHOP protocol due to budget, toxicity profile on par with clients’ willingness to assume risks of chemo, and schedule and time commitment. In some cases, it is to avoid drugs that target a patient’s weakness or concurrent illness. For example Lomustine is avoided with liver dysfunction and doxorubicin can cause cardiotoxicity so should be used cautiously in dogs with some pre-existing cardiac disease.
An Urban Experience
Alternative chemotherapy protocols include COP (vincristine, cyclophosphamide, and prednisone), single agent doxorubicin for B-cell lymphoma, and single agent Lomustine for T-cell lymphoma. These protocols generally have lower response rates ranging from 50- 80% and shorter remission durations of 6 to 7 months.
New therapies for lymphoma include monoclonal antibodies, a lymphoma vaccine, and Tanovea. It is hopeful these new therapies will increase survival
times. Canine remission times on CHOP have plateaued at about 9 months.
In human monoclonal antibodies are standard of care. Before rituximab, results of CHOP-based chemotherapy plateaued in human medicine. Since its launch in 1997
it is the standard of care for non-Hodgkin’s lymphoma
in humans and the addition of rituximab to standard CHOP has increased overall survival by 55%. More recently, monoclonal antibodies have been introduced as targeted therapy for both T- and B-cell canine lymphoma, but efficacy and administration schedule are still being worked out.
If chemotherapy is declined If chemotherapy is declined, another option is single agent steroids. Typical response rates are 50% with duration of 2 to 3 months. Prednisone should not be started prior to chemotherapy since it may decrease response rate to chemotherapy started after the steroids. Pre- chemotherapy steroids use is associated with shorter remission and survival times due to induction of multi-drug resistance. If staging tests are done after prednisone is started, higher stage patients may appear to be lower stage (down-stage). Without chemotherapy the prognosis for lymphoma is poor, with MST of 1 month.
Relapse The majority of lymphoma patients relapse as there is the emergence of tumor clones that are more resistant to chemotherapy, or survival-of-the-fittest lymphoma cells. These MDR (multi-drug-resistance) clones are more likely to express MDR-1 gene that encodes for protein transmembrane pump associated with multidrug resistance. Other reasons for relapse include inadequate chemotherapy dosing, inadequate chemotherapy frequency, or failure to achieve high chemotherapy concentrations at certain sites, such as the CNS.
When a patient relapses, I recommend reintroducing the initial protocol if it was successful, meaning the expected remission duration was achieved. For example, if a dog relapses one month after completing a CHOP protocol
I will not recommend restarting front-line chemotherapy. However if the dog was off chemotherapy for 4-5 months with a 1st remission of 9-10 months, I will recommend restarting the induction protocol as re-induction rates of 90% can be expected. Remember there is a cumulative dose of doxorubicin, so doxorubicin is typically
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