Adjuvant Doxorubicin with or without Metronomic Cyclophosphamide for Canine Splenic Hemangiosarcoma

Abstract

This retrospective study investigated the outcome of 33 dogs with splenic hemangiosarcoma treated with surgery followed by adjuvant dose-intensified doxorubicin (DOX) with or without low-dose metronomic cyclophosphamide (LDM-C) maintenance therapy. Among the 33 dogs, 18 dogs received LDM-C. Clinical stage was available for all dogs (5 stage I, 18 stage II, and 10 stage III). Nine dogs had macroscopic, and 24 dogs had microscopic disease at the start of DOX treatment. Median progression-free survival (PFS) and overall survival were 125 and 133 days, respectively. Clinical stage and tumor burden (microscopic versus macroscopic) at the start of chemotherapy was prognostic for PFS. No significant difference was observed in PFS or overall survival for the addition of LDM-C after a completed DOX protocol (P = .563 and P = .148, respectively). Based on the results of this retrospective study, the addition of LDM-C therapy as a maintenance regimen following a completed protocol of DOX adjuvant treatment of canine hemangiosarcoma may not improve outcome.

Adjuvant anthracycline‐based vs metronomic chemotherapy vs no medical treatment for dogs with metastatic splenic hemangiosarcoma: A multi‐institutional retrospective study of the Italian Society of Veterinary Oncology

“…However, the effectiveness of doxorubicin‐based protocols appears to have reached a plateau, with fewer than 10% of dogs diagnosed with hemangiosarcoma surviving 1 year after diagnosis . To aggravate clinical research, once hemangiosarcoma has spread to other sites, it has to be considered incurable, whereupon the role of adjuvant treatments is uncertain . Thus, identifying the population of dogs that may benefit from adjuvant chemotherapy is challenging.…”

“…During the past decade, enormous efforts have been devoted to overcoming the lethality of canine splenic hemangiosarcoma . However, the effectiveness of doxorubicin‐based protocols appears to have reached a plateau, with fewer than 10% of dogs diagnosed with hemangiosarcoma surviving 1 year after diagnosis .…”

“…Splenic hemangiosarcoma is characterized by rapid growth and early distant metastasis, with liver, lungs, peritoneum, and central nervous system sites commonly involved . The mainstay of therapy comprises surgery followed by adjuvant chemotherapy. Previous studies have shown that dogs with gross metastatic disease at the time of diagnosis (stage III) have shorter survival time (ST) compared with dogs with stage I or II disease . Reported median ST of dogs with stage III splenic hemangiosarcoma ranges from 27 to 65 days following splenectomy only .…”

“…Reported median ST of dogs with stage III splenic hemangiosarcoma ranges from 27 to 65 days following splenectomy only . The addition of adjuvant maximum‐tolerated dose chemotherapy (MTD), including an anthracycline as single agent, doxorubicin in combination with cyclophosphamide or dacarbazine, or doxorubicin in combination with vincristine and cyclophosphamide, resulted in median ST of 62 195 days. Overall, survival remains disappointing and most dogs will eventually succumb to progressive disease.…”

Retrospective comparison of first‐line adjuvant anthracycline vs metronomic‐based chemotherapy protocols in the treatment of stage I and II canine splenic haemangiosarcoma

“…In the present study, some dogs were treated with AC‐based chemotherapy and subsequently received treatment with MC. The use of cyclophosphamide‐based MC following an adjuvant protocol with DOX has been evaluated in 10 dogs with stage II splenic HSA and in subsequent studies including dogs with stage I to III splenic HSA receiving MC either sequentially or concurrently with DOX, although results were inconsistent. More recently, no survival advantage and a higher proportion of side effects was found when MC was used in combination with DOX …”