Preliminary study on a combined doxorubicin-dacarbazine chemotherapeutic protocol for the adjuvant treatment of canine hemangiosarcoma

Introduction Canine hemangiosarcoma shows high metastatic potential and short OS. The gold standard consists of surgery followed by doxorubicin-based chemotherapy. In this prospective study, we compared adjuvant doxorubicin-cyclophosphamide (AC) with doxorubicin-dacarbazine (ADTIC) chemotherapy to determine safety and efficacy. Methods Dogs with histologically-confirmed, surgically-removed and completely staged hemangiosarcoma were enrolled. Tumour characteristic, chemotherapy protocol, toxicity, TTM and OS were analyzed. Dogs were divided in Group 1 (AC) and in Group 2 (ADTIC). Results Sixteen dogs with biologically aggressive hemangiosarcoma were enrolled; 9 received AC (Group 1) and 7 had ADTIC (Group 2). In Group1, 2 dogs had BM toxicity (grade 1 and 3) and 4 had GI toxicity (grade 1-3). In Group 2, 5 dogs had BM toxicity (grade 2-4) and 2 had GI toxicity (grade 1-2). In Group 1, 8/ 9 dogs developed metastases; TTM was 90 days. In Group 2, 4/7 dogs developed metastases; TTM was 365 days. TTM increased in ADTIC group (p=0.094). In Group 1, 9/9 dogs died, 7 due to hemangiosarcoma; the mean OS was 90 days. In Group 2, 4/7 dogs died due to hemangiosarcoma and 3 dogs were alive at 450, 465 and 585 days. Group 2 showed a longer mean OS (P=0.066). Conclusions ADTIC group had a positive trend for TTM and OS compared with AC group. Cyclophosphamide and dacarbazine are both alkylating agents; however, dacarbazine shows increased fractional dose intensity, resulting in higher summation dose intensity of ADTIC compared with AC. Furthermore, ADTIC was well tolerated requiring no dose reductions.