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The use of DDVAP to reduce surgical metastases in mammary neoplasia of dogs
Perioperative desmopressin prolongs survival in surgically treated bitches with mammary gland tumours : A Pilot Study . Mermo GA et al . The Veterinary Journal 2016 ( 178 ) 103 -108
Summarised by : Dr Liesel van der Merwe BVSc ( Hons ) MMedVet ( Med ) Small Animals .
Why they did it ? Mammary tumours occur relatively commonly in the bitch . Approximately 40-50 % of mammary gland tumours are malignant and about 50 % of these are metastatic . The treatment of choice is surgical excision . Surgery and tissue trauma can enhance the growth and spread of malignant cells as manipulation can release viable cells into the circulation .
Desmopressin ( DDAVP ) is a synthetic derivative of ADH with haemostatic properties . It has been used in dogs and humans with diabetes insipidus and von Willebrands disease . The compound increases plasma levels of coagulation factor VIII , von Willebrand factor and tissue plasminogen activator ( tPA ) as well as enhancing platelet adhesion to the blood vessel endothelium . DDAVP decreased lung colonisation and dramatically decreased lymph node and distant metastases in a mouse model of breast tumour manipulation . The aim of this study was to test the efficacy of perioperative DDAVP on disease free and overall survival in surgically treated bitches with stage III or IV mammary neoplasia .
What they did ? Twenty one dogs were included in the study . Thoracic metastases were excluded based on radiography . Patients were randomly divided into a DDAVP group ( n = 11 ) and a placebo group . The DDAVP group was given 1 µ g / kg desmopressin in saline 30 minutes before and 24 hours after surgery . The placebo group was given an equivalent amount of saline at those same times . En bloc mastectomy of the affected gland ( s ), ipsilateral lymph nodes , as well as the glands cranially and caudal to the affected gland ( s ) was performed . Clinical follow up was done every 3 months for 12 months or when health issues required . Thorax metastases were diagnosed by a lateral and VD thoracic radiographs .
What they found ? Both groups of patients were similar with regard to clinical stage , tumour size and histopathological features . Three cases were excluded as they were found to have non-malignant masses : one from the DDAVP group and two from the placebo group . Four ( 36 %) patients in DDAVP group showed local relapses or lung metastases compared to eight ( 80 %) patients . Local recurrence was 9 % in the DDAVP group and 30 % in the placebo group and lung metastases was 27 % and 70 % respectively . DDAVP had a positive effect on median disease-free survival time . With the DDAVP group it was 608 days versus 85 days in the placebo group . Three patients in the DDAVP group and seven from the placebo group died during the study . The median overall survival time in the DDAVP group was > 600 days and in the placebo group was 333 days . Decreased intraoperative bleeding was subjectively noted in the DDAVP group .
Take Home message DDAVP may be used to minimise spread and / or survival of residual malignant cells released during cancer surgery .
A safety trial of DDAVP in human patients with breast cancer
A Phase II dose-escalation trial of perioperative desmopressin ( 1-desdamino-8-D-arginine vasopressin ) in breast cancer patients . Weinberg et al , SpringerPlus ( Open journal )( 2015 ) 4:428
Summarised by Dr Liesel van der Merwe BVSc MMedVet ( Med )
Why they did it ? DDVAP has haemostatic effects at doses as low as 0.2 – 0.3 µ g / kg which make it an often used treatment for bleeding disorders and it is also being evaluated as a blood saving agent in surgery or trauma . von Willebrands factor has emerged as a pivotal regulator of tumour cell metastases . It has been demonstrated that physiological levels induces apoptosis of metastatic cells after their “ arrest ” in the microvasculature of the target organ . Vasopressin receptors have been detected in many human cancer cell lines . It seems that DDVAP in the peri-operative phase not only inhibits perioperative metastatic events but also combats micrometastses that occurred before surgery .
What they did ? A Phase II dose escalation trial was conducted in patients with breast cancer , administering a lyophilized formulation of DDVAP by IV infusion in saline 30- 60 minutes before and 24 hours after surgery . Primary end points were safety and tolerability as well as selection of the best dose for surgery . Secondary endpoints were surgical bleeding , plasma levels of vWF and circulating tumour cells as measured by quantitiave PCR of cytokeratin transcripts . Twenty patients were entered in the trial . Median follow uptime was 24 months ( 17 – 39 months ).
What they found ? One patient developed hyponatraemia which normalised without treatment reversible and another showed hypersensitivity to the DDVAP . The patients were divided into 5 groups of 4 : the total doses were 0.5 ,µ g / kg , 1.0 µ g / kg , 1.25 µ g / kg , 1.5 µ g / kg and 2 µ g / kg . Drug reactions in the 2 µ g / kg group were managed by slowing the infusion time to 30 – 40 minutes . A Reduced intra-operative bleeding of up to 50 % was noted with increasing doses of DDVAP , measured by number and weight of swabs , and was more significant in patients receiving ≥ 1 µ g / kg DDVAP . vWF : Ag plasma levels increased by 50 – 100 % with maximum levels obtained in patients treated with 2 µ g / kg DDVAP . Circulating tumour cells could be evaluated in 16 patients . There was no dif- vet360
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