A Combination Chemotherapy Protocol (VELCAP‐L) for Dogs with Lymphoma

Abstract

Ninety-eight dogs with lymphoma treated with a 5-drug combination chemotherapy regimen (vincristine. L-asparaginase. cyclophosphamide. doxorubicin, prednisone [VELCAP-L]) were evaluated for pretreatment characteristics predictive for response and remission duration. The complete remission rate was 6970, with a median remission duration of 55 weeks. Dogs with advanced stage of disease, constitutional signs, dogs that were older, and dogs that were dyspneic were less likely to achieve remission. Once in remission, small dogs and dogs without pretreatment thrombocytopenia were likely to have longer remission duration. Toxicoses were frequent, but rarely fatal. and no predictitive factors were found for a dog developing toxicoses. VELCAP-L is an effective treatment for dogs in stage 1-111 lymphoma, particularly in young, small animals.Key words: Cancer: Remission; Treatment.ymphoma is the most common hematopoietic neo- Although maintenance therapy may be important for duration of remission, it appears that an aggressive induction protocol may also be important in determining both remission rate and duration. The ACOPA-11' protocol had an induction period designed to decrease toxicity and minimize patient visits; this protocol had a low remission rate, possibly due to its decreased dose intensity. The protocol VELCAP-L was designed to provide an intense induction period, followed by a maintenance protocol identical to that used in the ACOPA-I1 protocol (see Fig. 1). Materials and Methods Criteria for Selection of CasesOne hundred eleven dogs with a histologic or cytologic diagnosis of multicentric lymphoma and that had not received prior chemotherapy other than prednisone were eligible for entry into this study. Of these 1 I 1 dogs, 13 were excluded because of poor adherence to protocol or a change in diagnosis (from lymphoma to leukemia). The remaining 98 dogs were treated with the VELCAP-L combination chemotherapy protocol.

Impact of Chemotherapeutic Dose Intensity and Hematologic Toxicity on First Remission Duration in Dogs with Lymphoma Treated with a Chemoradiotherapy Protocol

“…Nonetheless, in numerous studies using intent-to-treat analyses, chemotherapy-related deaths are relatively rare despite frequent neutropenia. 5,6,22,23,37,41 Despite these findings, dose escalation clearly carries substantial risk and should not be used without additional research to confirm or refute the findings of this study.…”

“…Escalation of either the vincristine or cyclophosphamide dose may prove to be safe given that lymphoma protocols have been published that use these drugs at dosages higher than those used in this protocol. 6 As has been shown in other recent studies, an increase in nonhematopoietic toxicity may need to be considered in these situations, and concurrent sodium 2-mercaptoethane sulfonate or furosemide therapy might be needed if dose escalation is used with cyclophosphamide. 37,52,53 Preliminary evidence from our study indicates that clinically relevant neutropenia, such as that associated with fever or sepsis, is rare for patients in remission.…”

“…Remission duration may be affected by the chemotherapy drugs that are used in a protocol and the utility of consolidation radiation therapy. 5,6,38,41 When all patients receiving doxorubicinbased chemotherapy for lymphoma in the study hospital were assessed, variation in several areas, including dosing schedules, premature patient attrition, the use of radiation therapy, and owner compliance, made it difficult to reliably compare DI, myelotoxicity, and outcome. In an effort to evaluate a homogeneous population of dogs and thereby draw meaningful conclusions, stringent inclusion criteria were applied in this post hoc analysis.…”

“…[17][18][19][20][21] The exception to this rule is found in the treatment of lymphoma, for which doxorubicin-based multiagent protocols provide the longest reported survival times in both cats and dogs. 5,6,22,23 Not surprisingly, this is also the single example of an animal cancer for which 3 drug classes (ie, vinca alkaloids, alkylating agents, anthracyclines) are known to have substantial activity as single agents. [24][25][26] In addition to using multiple drugs, the maximization of dose intensity (drug dose/m 2 /wk) has proven to be of importance for improving the efficacy of chemotherapy for some human cancers.…”

“…[1][2][3][4][5][6][7][8] The rational design of multidrug protocols ideally follows a number of guidelines. 7 Each drug in the prescribed protocol should exhibit substantial activity as a single agent for the cancer in question.…”