A New Chemotherapy Protocol (Dose Intensifying Simultaneous Chemotherapy = Disc Protocol) for the Treatment of Canine Malignant Lymphoma: 21 Cases
Drug dosage, administration interval, as well as the combination of drugs with different mechanisms of action are the mainstays of successful chemotherapy. The aim of this study was to record toxicity profile, remission rates, and individual dosage levels of a Dose Intensifying Simultaneous Chemotherapy (DISC) protocol for dogs with lymphoma. Twenty one dogs with newly diagnosed and previously untreated lymphoma were included. Dogs were treated with a standardized protocol starting with L-asparaginase (day 0) followed by weekly simultaneous administration of vincristine, cyclophosphamide, and doxorubicin for a total of 12 treatments. Prednisolone was administered for 3 days and furosemide for 2 days with each simultaneous treatment. Dogs were treated at the same dosage level starting at 33% of the normal target dose of vincristine (0.7 mg/m²), cyclophosphamide (200 mg/m²), and doxorubicin (30 mg/m²) each for 2 cycles. If a grade 1 or no toxicity occurred, the dosages were increased to the next dosage level. All dogs were treated with dosage escalations of 5-7%, starting at 33%. Response distribution in the 21 patients was as follows: complete remission 17/21 (81%); partial remission 1/21 (5%); stable disease 2/21 (9%); progressive disease 1/21 (5%). This equals an overall remission rate of 86% and is comparable to other combination chemotherapy protocols. Only 1 dog was withdrawn from the protocol due to toxicity, 2 due to lack of response, all 3 at dosage level 33%, and 1 dog was euthanized because of progressive disease at dosage level 40%. Two dogs died of causes unrelated to disease or treatment. Only 3 dogs experienced 1 episode of grade 4 toxicity each: 1 case of asymptomatic neutropenia (dosage level 45%), 1 of asymptomatic thrombocytopenia (dosage level 45%) and 1 septic episode in a diabetic dog (dosage level 33%). Other signs of toxicity were infrequent and mild (grade 1 and 2, rare asymptomatic grade 3 thrombocytopenia or anemia), with only 2 dogs requiring hospitalization for less than 48 hours. The highest dosage level of 60% was achieved in 1 dog. Four dogs reached 33%, 2 dogs 40%, 4 dogs 45%, 2 dogs 50% and 5 dogs 55 % as the highest level. Highest dosage level is not yet reached in 2 dogs currently on the protocol. Median remission and survival times have not been reached at submission of this abstract. Toxicity events and remission rates of the DISC protocol are comparable to other polychemotherapy protocols. This protocol has shown a wide difference of individual dosage tolerance and further studies are needed to compare treatment outcome to that of established chemotherapy protocols.