Page 564 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

542 PART IV Specific Malignancies in the Small Animal Patient

RT in dogs with appendicular OSA is for palliation of bone pain. with neutropenia identified as the dose-limiting toxicity. For the
RT at relatively high total doses can cause considerable necrosis entire study population, the median DFI and MST were 257 and
321 days, respectively. For dogs receiving the planned four doses
of primary OSA in dogs and people either before LSS to down-
VetBooks.ir stage the primary tumor to improve the success of local disease of carboplatin, median DFI and MST were extended to 327 and
383 days, respectively.
control after removal or as a primary therapy for unresectable
tumors. 203,205,262–264 As a primary therapy, a MST of 209 days Despite the initial report of carboplatin’s comparable activity
was reported in 14 dogs with appendicular OSA treated with frac- to cisplatin, 160 two prospective randomized studies using single-
tionated high-dose RT (median dose of 57 Gy) to their primary agent carboplatin as a comparator arm demonstrated less impres-
tumor and systemic chemotherapy. 265 The introduction of SRT sive antimetastatic effects. 268,269 In one study, dogs were treated
has allowed for delivery of high doses of radiation to the tumor with a single neoadjuvant dose of carboplatin and amputation 7
volume with good local tumor control and relative sparing of the days later, then received two additional treatments with carbopla-
2
surrounding normal tissues. tin (300 mg/m ) every 21 days. Upon completion of carboplatin,
dogs were then randomized to receive either placebo or a long-
Radioisotopes acting somatostatin analog. 268 For dogs treated with carboplatin
153
A beta emitter radioisotope, Sm-EDTMP, has been used to treat and placebo, the median DFI and MST were 196 and 230 days,
primary OSA and metastatic bone neoplasia in dogs and humans respectively. In a second study comparing the activity of a lipo-
via systemic IV administration. Yttrium-hydroxide (Y90) has some-encapsulated cisplatin formulation (SPI-77) versus single-
90
been reported as an intralesional liquid brachytherapy in a dog agent carboplatin, 40 dogs were treated with a single neoadjuvant
90
with tibial OSA. Y was deposited locally in the bone, bone mar- dose of either SPI-77 (350 mg/m ) or carboplatin (300 mg/m )
2
2
row, and soft tissue components of the tumor using specialized 1 week before amputation and then received an additional three
cannulas. Localized, high-dose RT can be delivered in such a man- treatments of SPI-77 or carboplatin every 21 days. 269 No differ-
ner, and, in addition, a minor portion of the breakdown product ence was identified between treatment groups; dogs treated with
90
of Y can be imaged by PET/CT to confirm the presence of the single-agent carboplatin had a median DFI and ST of 123 and
agent at the tumor site. 266,267 207 days, respectively.
Two relatively large retrospective studies have been conducted
Systemic Adjuvant Therapy for Dogs with to substantiate the activity of carboplatin for managing pulmo-
Osteosarcoma nary micometastases. 270,271 In a study initiated by the Veterinary
Cooperative Oncology Group (VCOG), 155 dogs treated with
For the most effective management of canine OSA, multimodal- amputation and carboplatin (variable dosage and schedule) had
ity therapy is required to address both local and metastatic disease. a median DFI and STs of 256 and 307 days, respectively. 270 In a
Although amputation and LSSs, as well as nonsurgical techniques second retrospective investigation, 65 dogs treated with amputa-
such as SRT, have proven highly effective for local OSA manage- tion and carboplatin at a dosage of 300 mg/m every 21 days for
2
ment, the ability to cure or durably control OSA metastases remains four to six treatment cycles had a median DFI and ST of 137 and
a clinical challenge; substantive improvements in DFIs and STs 277 days, respectively. 271
await advances in systemic antimetastatic treatment options.
Although systemic chemotherapy remains the backbone for Single-Agent Doxorubicin Chemotherapy
the management of OSA metastases, it is improbable that the DOX is considered effective for delaying the development and
discovery of new chemotherapeutic agents or dose-intensification progression of metastatic disease in dogs with OSA. The anti-
with existing agents will dramatically improve current clinical metastatic effects of DOX are more definitively substantiated
outcomes. Rather, the future of OSA management will likely when administered every 2 weeks rather than every 3 weeks. In
2
depend on combining conventional cytotoxic agents with tar- one study, DOX was administered at a dose of 30 mg/m every 2
geted molecular therapeutics or immunomodulatory agents. As weeks for five treatments to 35 dogs with appendicular OSA in a
such, considerable research focus has been committed to discover- neoadjuvant setting. Dogs were treated with two or three doses of
ing and validating new combination therapies for improving the DOX before amputation and continued to receive DOX postop-
long-term prognosis of canine OSA. eratively for a total of five treatments. 272 The 1- and 2-year survival
rates were 50.5% and 9.7%, respectively. In a second study evalu-
Chemotherapy ating the activity of a matrix metalloproteinase inhibitor (BAY
Table 25.2 provides an abbreviated summary of conventional che- 12-9566), 303 dogs were treated with amputation and DOX (30
motherapeutic agents used in the adjuvant setting, evaluated as mg/m every 2 weeks for a total of five treatments), and then ran-
2
single agents or in combination. Table 25.2 is not an exhaustive domized to receive a daily oral placebo or BAY 12-9566. 180 No
description of all reported studies conducted to date, but rather difference in ST was identified between dogs receiving placebo or
presents findings from studies derived from sample populations of BAY 12-9566, and the overall MST was 8 months.
greater than 20 dogs per investigation.
Doxorubicin-Carboplatin Combined Chemotherapy
Single-Agent Carboplatin Chemotherapy Given the modest to severe toxicity associated with DOX-
Carboplatin is a second-generation platinum compound that cisplatin combination therapy, 273,274 one study investigated if
is less nephrotoxic than cisplatin. Given its ease of administra- combination tolerability could be improved by replacing cis-
tion, carboplatin has largely supplanted the use of cisplatin in the platin with carboplatin. The rationale to use carboplatin was
postoperative setting. In the first study reporting the tolerability based upon its comparable anticancer activities and improved
and activity of carboplatin, 48 dogs with OSA were treated with side effect profile relative to cisplatin, which removes the need
amputation and intent-to-treat with four doses of carboplatin for saline diuresis and minimizes the likelihood of severe
2
(300 mg/m every 21 days). 160 Carboplatin was well-tolerated emesis. Twenty-four dogs were treated with definitive surgery