imperative when administering vesicants. Potent vesicants (doxorubicin, dactinomycin, vinca alkaloids) should be flushed with a minimum of 6 ml of saline before removing the intravenous (IV) needle or catheter. Doxorubicin should always be administered via an in‐dwelling IV catheter, while less severe vesicants and irritants may be safely administered through a carefully placed butterfly catheter. Some oncologists advocate for administration of all agents via an IV catheter. As a rule, vesicant chemotherapeutics should never be administered via an unattended/unmonitored fluid or syringe pump. Instead, the catheter site must be visually monitored for continued proper placement and periodically checked for patency with aspiration/saline flushes prior to, during, and after vesicant drug administration.
Modalities include surgery, radiation therapy, surgery combined with radiation therapy, photodynamic therapy, imiquimod, intralesional chemotherapy (alone or combined with hyperthermia or radiation), electrochemotherapy (ECT) with bleomycin, ECT with bleomycin and doxorubicin, vitamin A–related synthetic retinoids. Cryosurgery is used for small lesions, and there are partial responses with piroxicam in dogs.
Intranasal Carcinoma
Median survival time (MST) without treatment is 95 days; MST of 107 dogs with epistaxis was 88 days versus 224 days for 32 dogs without epistaxis (Rassnick et al. 2006). For curative‐intent radiation therapy (RT), MST is approximately 8–20 months (Adams et al. 1987, 1998, 2005; Evans et al. 1989; Theon et al. 1993; LaDue et al. 1999; Nadeau et al. 2004). However, in one study the MST for nasal carcinomas treated with curative intent RT was only 4.4 months, and dogs with unilateral intranasal involvement without bone destruction beyond the turbinates on computed tomography (CT) had a MST of 23.4 months, versus 6.7 months for dogs with CT evidence of cribriform plate involvement (Adams et al. 2009). Curative‐intent RT followed by surgical debulk (13 dogs) has MST of 47 months in one study (Adams et al. 2005), and 15 months in another (Bowles et al. 2014). In another study, 42 dogs with nasal tumors treated with surgical cytoreduction and orthovoltage RT had a MST of 7.4 months (Northrup et al. 2001). Curative–intent RT with CT planning has MST of approximately 11–20 months. Coarse‐fraction RT (56 dogs) has MST of 7 months (Mellanby et al. 2002), 4.8 months in another study of 48 dogs (Gieger et al. 2008), 16.8 months (although the majority were carcinomas, there were several sarcomas in the study) (Fujiwara et al. 2013), and 6.5 months (with no significant difference with or without cribriform plate involvement) (Maruo et al. 2011). Hypofractionated image‐guided robotic stereotactic radiotherapy either with or without adjunctive treatment for nasal tumors (79% were carcinomas) resulted in a MST of 13.5 months (Glasser et al. 2014), and 10.4 months for nasal carcinomas in another study (Kubicek et al. 2016). In another study of non‐lymphomatous nasal tumors in dogs treated with hypo‐fractionated image‐guided robotic stereotactic radiotherapy without adjunctive chemotherapy, the MST was 19.3 months, and was not significantly different for carcinomas versus sarcomas, or dogs with intracranial extension of disease (Gieger and Nolan 2017). In another study of 12 dogs (75% of dogs had intranasal carcinomas) treated with intensity‐modulated RT, the MST was 15.3 months (Hunley et al. 2010), and at least one eye could be saved in all dogs treated with intensity‐modulated RT in another study (Vaudaux et al. 2007), and both eyes were spared in another study with MST of 13.8 months (Lawrence et al. 2010). Palliative 3D conformal RT (38 dogs) has overall median progression‐free interval of 10 months (Buchholz et al. 2009). Palliative RT in another study resulted in 10.2 months MST (although 39% of the dogs in this study had nasal sarcomas) (Tan‐Coleman et al. 2013). Chemotherapy alone (small numbers of dogs) is investigational (Hahn et al. 1992; Langova et al. 2004). In a study of 37 dogs with reirradiation of nasal carcinomas, the MST from the first dose of RT was 14.9 months and 5.9 months from the first dose of the second course of RT (Gieger et al. 2013). Reirradiation in another study resulted in an overall MST of 2.5 years (Bommarito et al. 2011). Use of radiation sensitizers (some investigational) is generally not better than RT alone. Other treatments include brachytherapy, immunotherapy, cryotherapy, and PDT (all investigational) (MacEwen et al. 1977; White et al. 1990; Thompson et al. 1992; Lucroy et al. 2003b). Slow‐release cisplatin and RT for nasal tumors resulted in MST of 15.6 months (35% of tumors were sarcomas in this study) (Lana et al. 2004). High‐dose‐rate brachytherapy in 15 dogs (not of which had nasal carcinomas) resulted in a 17‐month MST (Klueter et al. 2006). Primary frontal sinus squamous cell carcinoma in three dogs treated with piroxicam combined with carboplatin or toceranib (investigational in 3 dogs) (de Vos et al. 2012). Nasal carcinoma treated with RT and firocoxib was safe and improved life quality in dogs with nasal carcinomas (Cancedda et al. 2015b).
Transitional Cell Carcinoma (Urogenital)
Bladder/urethra (dogs): Surgery: Surgery includes debulk, stent, bypass (e.g. pre‐pubic cystostomy catheter for palliation if obstructed), total cystectomy and urinary diversion, resection of proximal urethra and bladder neck and bilateral ureteroneocystostomy (Saulnier‐Troff et al. 2008), partial cystectomy alone or in combination with unilateral or bilateral ureteral reimplantation (Stone et al. 1996; Marvel et al. 2017). Rarely is there complete excision due to urethral, prostatic, or ureteral involvement. Surgery is generally combined with chemotherapy to improve survival; MST chemotherapy and surgery 475 days, versus chemotherapy alone MST 31 days, versus surgery alone MST 240 days, versus no treatment MST 7 days (Molnar and Vajdovich 2012). Partial cystectomy: 14 dogs treated with partial cystectomy with or without any adjuvant treatment, the MST was 113 days (Norris et al. 1992). Partial cystectomy and long‐term piroxicam (92%) or carprofen (8%) +/− various chemotherapeutic agents were used in 37 dogs with bladder TCC, achieving a MST was 348 days (Marvel et al. 2017). Total cystectomy: Total cystectomy followed by ureterocolonic anastomosis was performed in 10 dogs with TCC the overall prognosis was poor with adverse effects such as severe vomiting and neurologic signs (Montgomery and Hankes 1987; Stone et al. 1988). Total cystectomy and urinary diversion to the vagina have been reported, although persistent urinary incontinence is expected (Boston and Singh 2014; Saeki et al. 2015). Total cystectomy and urinary diversion to vagina or prepuce (with post‐operative chemotherapy) resulted in a MST of 385 days in 10 cases, and although there were fewer gastrointestinal and neurologic complications compared to ureterocolic anastomosis, dehiscence of ureterostomy, pyelonephritis, oliguria, azotemia, ureteral obstruction, and persistent urinary incontinence were reported post‐operative issues (Saeki et al. 2015). Total cystectomy and bilateral cutaneous ureterostomy in 4 dogs had a MST of 279 days (Ricardo Huppes et al. 2017). Resection of proximal urethra and bladder neck and bilateral ureteroneocystostomy: One dog treated with this surgery and adjuvant chemotherapy survived 580 days (Saulnier‐Troff et al. 2008). Debulking surgery: Debulking surgery alone for bladder TCC had a MST of 109 days (Lengerich et al. 1992). Debulking surgery performed by ultrasound‐guided endoscopic diode laser ablation of TCC bladder/urethra in dogs and post‐operative carprofen or piroxicam (given for an unknown duration) had MST 380 days, however, complications included stranguria, hematuria, stenosis, spread of TCC within the lower urinary tract, urethral perforation, and bacterial cystitis (Cerf and Lindquist 2012). Debulking surgery using carbon dioxide laser ablation of bladder TCC (via laparotomy) combined with mitoxantrone and piroxicam achieved a MST of 299 days, with rapid resolution of clinical signs (Upton et al. 2006). In another study, 34 dogs with TCC of the urinary bladder and/or prostate and/or urethra were treated with between one and six doses of doxorubicin concurrently with piroxicam, and 50% of these cases also had surgery (mostly curative intent). Of the 23 dogs with measurable disease, 14 had stable disease, 7 had progressive disease and 2 had a partial response. After documented progression of disease, 15 dogs received additional chemotherapy, consisting of carboplatin (n = 8), mitoxantrone (n = 6), vinorelbine (n = 1) or silibinin (n = 1). Overall median progression‐free survival was 103 days, and MST was 168 days. Cytoreductive surgery did not result in prolongation of progression‐free survival, but significantly prolonged overall survival, with chemotherapy and surgery resulting in a MST of 217 days versus chemotherapy alone MST 133 days (Robat et al. 2013a). Stenting: Stenting of 12