Tiludronate infusion in the treatment of bone spavin: A double blind placebo‐controlled trial

Reasons for performing study: Tiludronate regulates bone remodelling through a decrease of the resorptive process and should therefore ameliorate the remodelling processes active in osteoarthritis of the distal tarsal joints (‘bone spavin’) and alleviate pain associated with abnormal bone lysis. Objective: To confirm the efficacy of tiludronate, administered as a single infusion at a dose of 1 mg/kg bwt, in the treatment of bone spavin in the horse. Methods: A double blind placebo controlled trial on 108 clinical cases of bone spavin was undertaken. The lameness score of the lamest limb was assessed following distal tarsal analgesia of the contralateral limb and followed‐up using the same procedure throughout the study. Bone spavin in the lamest limb was confirmed by distal tarsal analgesia and radiography. Horses were treated at Day 0 and reassessed 60 days later after controlled exercise. A second nonblinded treatment was given to unresponsive horses and all horses were re‐examined at Day 120. Exercise levels were recorded at each examination. Results: Eighty‐seven horses completed the trial as per the protocol. The tiludronate horses were significantly less lame than the placebo horses (P = 0.0318). Horses treated at Day 60 with tiludronate showed further improvement in lameness at Day 120 (P = 0.0096 and P = 0.0034 for horses treated with tiludronate and placebo at Day 0, respectively). The only significant difference in radiographic findings between tiludronate and placebo was for presence of periarticular osteophytes (P = 0.006). Conclusions: Tiludronate treatment is proven to be effective in bone spavin in horses in association with a controlled exercise programme. Clinical relevance: Tiludronate in combination with controlled exercise offers an alternate medical treatment for bone spavin.     

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

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.     

Concentration profiles and safety of topically applied betulinic acid and NVX‐207 in eight healthy horses—A randomized,blinded, placebo‐controlled,crossover pilot study

The naturally occurring betulinic acid (BA) and its derivative NVX‐207 show anticancer effects against equine malignant melanoma (EMM) cells and a potent permeation in isolated equine skin in vitro. The aim of the study was to determine the in vivo concentration profiles of BA and NVX‐207 in equine skin and assess the compounds’ local and systemic tolerability with the intent of developing a topical therapy against EMM. Eight horses were treated percutaneously in a crossover design with 1% BA, 1% NVX‐207 or a placebo in a respective vehicle twice a day for seven consecutive days with a seven‐day washout period between each formulation. Horses were treated at the neck and underneath the tail. Concentration profiles of the compounds were assessed by high‐performance liquid chromatography in the cervical skin. Clinical and histopathological examinations and blood analyses were performed. Higher concentrations of NVX‐207 were found in the skin compared to BA. Good systemic tolerability and only mild local adverse effects were observed in all three groups. This study substantiates the topical application of BA and NVX‐207 in further clinical trials with horses suffering from EMM; however, penetration and permeation of the compounds may be altered in skin affected by tumors.