Doxorubicin and cyclophosphamide for the treatment of canine lymphoma: a randomized, placebo-controlled study*

Abstract

Median survival times (STs) for doxorubicin-treated canine lymphoma range from 5.7 to 9 months. Because dogs treated with multi-agent protocols have longer STs, we sought to evaluate whether adding cyclophosphamide would improve outcome in canine lymphoma patients while maintaining an acceptable level of toxicity. Thirty-two dogs with stage III–V multicentric lymphoma were treated with doxorubicin every 3 weeks for five total cycles and prednisone at a tapering dose for the first 4 weeks. Dogs were randomized to receive either cyclophosphamide or placebo concurrently. Seventeen dogs received doxorubicin and placebo, while 15 dogs received doxorubicin and cyclophosphamide. Response, toxicity, progression-free interval (PFI) and ST were evaluated. The combination of doxorubicin and cyclophosphamide was well tolerated, causing no increase in adverse events over doxorubicin alone. Despite a numeric improvement in outcome in cyclophosphamide treated dogs, the addition of cyclophosphamide did not result in statistically improved response rate, PFI or ST.

A comparison of 12‐ and 19‐week CHOP protocols using non‐randomized, contemporaneous controls

“… Using a neutrophil count of 1500 cells/μL and above to permit chemotherapy administration was described by Fournier et al as a clinically appropriate cut‐off that would permit the most condensed length of each overall treatment in each protocol, and thus, provide the highest potential DI. Furthermore, it is generally believed that anthracyclines are the most efficacious component of CHOP protocols and we felt that the increased DI of DOX in our CHOP12 would offset any diminished efficacy associated with the lower VCR DI. While our “delivered” DI of DOX and CTX was not as high as planned in our CHOP12 owing to AEs inherent in CHOP‐based treatment, we still achieved 35% DOX and 40% CTX dose intensification over our target DI for the standard 19‐week protocol.…”

Phase I clinical trial and pharmacodynamic evaluation of combination hydroxychloroquine and doxorubicin treatment in pet dogs treated for spontaneously occurring lymphoma

“…These results are encouraging given that reported response rates with DOX alone for treatment-naive lymphoma in dogs range from 60% to 85%. 41,42 The median progression-free interval in dogs with lymphoma in this study was 5.0 mo which is comparable to single agent DOX at 30 mg/m 2 . 41,42 A larger study group with longer follow-up would be required to determine if the combined HCQ and lower DOX (25 mg/m 2 ) dose is superior, or at least as effective, as single agent DOX administered at the standard 30 mg/m 2 dose.…”

“…39 Owing to toxicity and cost of multiagent chemotherapy, single agent doxorubicin is a frequently used alternative that produces a substantially lower response rate of 63 to 85% and a median progression-free survival of approximately 5 mo. [41][42][43] Although there have been reports of enhancement of antitumor activity with combinations of cytotoxic drugs and autophagy inhibition in vitro and with in vivo mouse models, there are no reports on the clinical utility of autophagy inhibition using HCQ in canine cancer patients. Here we report the results of a Phase I/II clinical trial of oral HCQ given continuously, starting 72 h prior to a standard dose of DOX.…”

Clinical response to a lomustine/cytarabine-based chemotherapy protocol in a case of canine large granular lymphocyte T-cell lymphoma with spinal involvement

“…Ultimately, a single agent anthracycline was chosen to treat signs of relapse given it was not included in the original protocol. The use of doxorubicin alone or in combination has been previously described to treat canine patients with relapsed lymphoma (Calvert and Leifer, 1981;Lori et al, 2010) and epirubicin has been used in a multidrug protocol to treat dogs with naïve lymphoma (Elliott et al, 2013). No other rescue protocols or consolidation of the above were tried as the owner had decided to discontinue treatment, but the authors cannot exclude that further chemotherapy may have resulted in prolonged remission and survival times, and can therefore be considered in a similar case.…”