Concomitant Liposomal Doxorubicin and Daily Palliative Radiotherapy in Advanced Feline Soft Tissue Sarcomas

Abstract

Local recurrence of feline soft tissue sarcomas is common despite aggressive treatment. Liposomal doxorubicin might serve as a depot radiosensitizer if administered concomitantly with daily radiotherapy and thus improve tumor control. In this pilot study, the feasibility of concomitant liposomal radiochemotherapy was evaluated in a palliative setting in 10 cats with advanced soft tissue sarcomas. Cats were treated with median number of 5 (range 5-7) daily fractions of radiotherapy and a median total dose of 20 Gy (range 20-31.5 Gy). One dose of liposomal doxorubicin was administered at the beginning of radiotherapy. Seven cats received further free or liposomal doxorubicin after completion of the liposomal doxorubicin/radiation protocol. Seven of the treated 10 cats (70%) achieved a partial (n=5) or complete (n=2) response with a median response duration of 237 days. The median progression free interval in all 10 cats was 117 days and the median overall survival time was 324 days. Concomitant liposomal radiochemotherapy was tolerated well in nine cats, one cat experienced temporary anorexia. Although the number of patients is too small to make definitive conclusions, results appear promising enough to investigate the role of liposomal doxorubicin as a radiosensitizer further.

Current knowledge on feline injection-site sarcoma treatment

“…In a pilot study including 10 cats with advanced FISS, it was shown that liposomal doxorubicin used with palliative daily fraction radiotherapy could also be used as a depot radiosensitizer [37]. Additionally, in a study performed on 12 cats with non-resectable FISS, combining doxorubicin with cyclophosphamide resulted in a partial response in 50% of cats and significant improvement in the survival time of responders [38].…”

Recent Developments in Liposome-Based Veterinary Therapeutics

“…Despite observable increases of drug levels at tumour sites, the clinical outcomes of human patients treated with liposome-encapsulated Doxorubicin have been the same as those treated with free Doxorubicin [15, 16]. The low response rate of these liposomal formulations was purported to be due to a lack of understanding of drug release from the liposomes [17]. …”

“…Due to liposome-based drugs having longer in vivo circulations, sensitizing agents can be loaded into liposomes to serve as potent pretreatment sensitizers for radiotherapy in cancer. A study conducted in 2010 demonstrated improved therapeutic outcomes in cats with advanced feline soft tissue sarcomas when given liposomal Doxorubicin concomitantly with daily palliative radiotherapy [17]. Liposomal Doxorubicin has been shown to sensitize tumour cells to concomitantly administered radiotherapy [17].…”

“…A study conducted in 2010 demonstrated improved therapeutic outcomes in cats with advanced feline soft tissue sarcomas when given liposomal Doxorubicin concomitantly with daily palliative radiotherapy [17]. Liposomal Doxorubicin has been shown to sensitize tumour cells to concomitantly administered radiotherapy [17]. Despite the small sample size ( n = 10), the results were encouraging with 7 cats achieving partial ( n = 5) or complete ( n = 2) response for a duration of 237 days [17].…”

“…Liposomal Doxorubicin has been shown to sensitize tumour cells to concomitantly administered radiotherapy [17]. Despite the small sample size ( n = 10), the results were encouraging with 7 cats achieving partial ( n = 5) or complete ( n = 2) response for a duration of 237 days [17]. In addition to Doxorubicin, other antineoplastic agents have also been studied as liposome-encapsulated formulations.…”