Rabacfosadine for relapsed canine B-cell lymphoma: Efficacy and adverse event profiles of 2 different doses.

Rabacfosadine (RAB), a novel double prodrug of the acyclic nucleotide phosphonate PMEG, preferentially targets neoplastic lymphocytes with reduced off target toxicity. Historical studies have suggested that every 21-day dosing is effective with acceptable toxicity. The purpose of this study was to evaluate RAB's safety and efficacy at 2 different doses every 21 days in dogs with relapsed B-cell lymphoma. Dogs that had failed 1 doxorubicin-based chemotherapy protocol were eligible for inclusion in this prospective trial. Once enrolled, dogs were randomized to receive RAB at either 0.82 mg/kg or 1.0 mg/kg as a 30-minute IV infusion every 21 days for up to 5 treatments. Response assessment and adverse event (AE) evaluation were performed every 21 days via VCOG criteria. Fifty dogs were enrolled, with 16 treated at 0.82 mg/kg and 34 treated at 1.0 mg/kg. The overall response rate was 74%, with 45% of dogs experiencing a complete response (CR). The median progression free intervals (PFIs) were 108 days, 172 days and 203 days for all dogs, all responders, and all CRs, respectively. Response rates and PFIs were similar in both treatment groups. The incidence of AEs, dose delays, dose reductions and withdrawals were not statistically different between the 2 groups. The AEs observed were similar to those previously reported and included hematologic, gastrointestinal, dermatologic and pulmonary AEs. One dog had grade 5 pulmonary fibrosis; otherwise, AEs resolved with supportive treatment. Rabacfosadine is a generally well tolerated, effective chemotherapy option for dogs with relapsed B-cell lymphoma.

Doxorubicin chemotherapy for presumptive cardiac hemangiosarcoma in dogs†.

Sixty-four dogs were treated with single-agent doxorubicin (DOX) for presumptive cardiac hemangiosarcoma (cHSA). The objective response rate (CR + PR) was 41%, and the biologic response rate (CR + PR + SD), or clinical benefit, was 68%. The median progression-free survival (PFS) for treated dogs was 66 days. The median survival time (MST) for this group was 116 days and was significantly improved compared to a MST of 12 days for untreated control dogs (P = 0.0001). Biologic response was significantly associated with improved PFS (P < 0.0001) and OS (P < 0.0001). Univariate analysis identified larger tumour size as a variable negatively associated with PFS. The high rate of clinical benefit and improved MST suggest that DOX has activity in canine cHSA.

Dose-escalating vinblastine for the treatment of canine mast cell tumour.

The purpose of this study was to evaluate the short-term adverse events (AEs) in dogs with mast cell tumours (MCT) receiving prednisone and dose-escalating vinblastine (VBL). Twenty-four dogs were treated with intravenous VBL starting at 2 mg m(-2) and then escalating in weekly increments to 2.33, 2.67 and 3 mg m(-2). AEs were graded using a standardized scoring system. No dogs receiving 2 or 2.33 mg m(-2) experienced grade 3 or 4 AEs. Among the dogs, 9.5 and 5.9% had grade 3 or 4 AEs at dosages of 2.67 and 3 mg m(-2), respectively. Serious AEs included neutropaenia (n = 3) and vomiting (n = 1), only one of which required hospitalization. These data indicate that VBL chemotherapy may be safe to administer at higher than the traditional 2 mg m(-2) dosage for dogs with MCT. Randomized prospective trials are necessary to establish whether dose escalation will translate into improved response rates when compared with the standard 2 mg m(-2) dosage.

Allelic variants of the follistatin gene in polycystic ovary syndrome.

In an earlier study of 37 candidate genes for polycystic ovary syndrome (PCOS), the strongest evidence for genetic linkage was found with the region of the follistatin gene. We have now carried out studies to detect variation in the follistatin gene and assess its relevance to PCOS. By sequencing the gene in 85 members of 19 families of PCOS patients, we found sequence variants at 17 sites. Of these, 16 sites have variants that are too rare to make a major contribution to susceptibility; the only common variant is a single base pair change in the last exon at a site that is not translated. In our sample of 249 families, the evidence for linkage between PCOS and this variant is weak. We also examined the expression of the follistatin gene; messenger RNA levels in cultured fibroblasts from PCOS and control women did not differ appreciably. We conclude that contributions to the etiology of PCOS from the follistatin gene, if any, are likely to be small.