Thirty-nine, older, large-breed dogs with multilobular osteochondrosarcoma (MLO) each presented primarily with a fixed mass involving the flat bones of the skull. Twenty-five dogs were treated with surgical resection alone, nine were treated with adjuvant therapy, and five were not treated. Forty-seven percent of dogs treated had local tumor recurrence, and 56% had metastasis. Median time to recurrence, median time to metastasis, and median survival time were 797, 542, and 797 days, respectively. Histological grade, surgical margins, and tumor location affected outcome. Long-term remission can be obtained with aggressive treatment of MLO, although it is locally invasive and moderately metastatic.

Significant differences between the 2 treatment groups were not detected. The efficacy of doxorubicin in the treatment of vaccine-associated sarcomas is uncertain.

Seventy-one dogs with histologically confirmed appendicular osteosarcoma were evaluated. Seventeen dogs were treated with amputation and two dogs received postoperative doses of IV cisplatin given 21 days apart (group 1). Nineteen dogs were treated with IV cisplatin 21 days before amputation, with a second dose given immediately after amputation (group 2). Thirty-five dogs were treated by amputation of the affected limb with no chemotherapy (group 3). The median disease-free interval for group 1 was 226 days, and 177 days for group 2. This was not significantly different. The median survival time was 262 days for group 1,282 days for group 2 and 119 days for group 3. Group 1 and 2 dogs had survival times that were significantly longer than for dogs in group 3. Two IV courses of cisplatin given before or after amputation appears to improve the survival of dogs with osteosarcoma. (Journal of Veterinary Internal Medicine 1991; 5205-210) OSTEOSARCOMA (0s) is the most common primary bone cancer in dogs.',2 It accounts for approximately 4% of all canine neoplasms and has been estimated to affect approximately 7.9/ 100,000 dogs annually.' Treatment has generally included amputation, which relieves local discomfort but rarely results in a cure, with reported mean or median survivals of 3.6 to 5.8 ~~~~~ ~

Purpose: To determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic characteristics of doxorubicin encapsulated in a low temperature sensitive liposome (LTSL) when given concurrently with local hyperthermia to canine solid tumors. Experimental Design: Privately owned dogs with solid tumors (carcinomas or sarcomas) were treated. The tumors did not involve bone and were located at sites amenable to local hyperthermia. LTSL-doxorubicin was given (0.7-1.0 mg/kg i.v.) over 30 minutes during local tumor hyperthermia in a standard phase I dose escalation study. Three treatments, given 3 weeks apart, were scheduled. Toxicity was monitored for an additional month. Pharmacokinetics were evaluated during the first treatment cycle. Results: Twenty-one patients were enrolled: 18 with sarcomas and 3 with carcinomas. Grade 4 neutropenia and acute death secondary to liver failure, possibly drug related, were the doselimiting toxicities. The maximum tolerated dose was 0.93 mg/kg. Other toxicities, with the possible exception of renal damage, were consistent with those observed following free doxorubicin administration. Of the 20 dogs that received z2 doses of LTSL-doxorubicin, 12 had stable disease, and 6 had a partial response to treatment. Pharmacokinetic variables were more similar to those of free doxorubicin than the marketed liposomal product. Tumor drug concentrations at a dose of 1.0 mg/kg averaged 9.12 F 6.17 ng/mg tissue. Conclusion: LTSL-doxorubicin offers a novel approach to improving drug delivery to solid tumors. It was well tolerated and resulted in favorable response profiles in these patients. Additional evaluation in human patients is warranted.Liposome-encapsulated chemotherapy was developed to improve selectivity of drug for tumor compared with normal tissue. Despite the achievement of tumor drug levels that are up to 10-fold higher than those achieved with unencapsulated drugs, particularly when given concurrently with hyperthermia, clinical efficacy of these agents has been only modestly improved (1 -4). Decreased toxicity, in particular the cardiotoxicity seen with doxorubicin, has been the most significant benefit derived from these formulations.One potential explanation for the lack of clinical benefit from liposomal drug delivery to the tumor tissue is the dependence of cytotoxicity on the presence of free drug. Although the liposomes may accumulate preferentially in tumors, the mechanisms by which traditional liposomes release their contents are not well understood (5). The development of liposomes engineered for triggered drug release is one approach that addresses this problem directly.The development of hyperthermia-mediated drug release from liposomes was first reported in 1978 (6). These early thermosensitive liposomes typically released their contents at temperatures > 42jC. Temperatures in this range are difficult to achieve uniformly in a clinical setting. In addition, drug release was slow, requiring 30 minutes to release 40% of the contents (7). Because of...

When external beam radiation therapy is administered to the pelvis, normal tissues irradiated may include the colon, small intestine, urethra, bladder, bone, and spinal cord. The objectives of this retrospective study were to determine the incidence and severity of late radiation effects following pelvic irradiation in dogs and to identify factors that increase the risk of these effects. Medical records of all dogs treated with curative intent external beam radiation therapy to the pelvic region between 1993 and 1999 were reviewed. Patients with follow-up longer than 9 months or any patient that developed late complications earlier than 9 months were evaluated. Sixteen dogs met criteria for inclusion in this study. All dogs were treated with a 6-MV linear accelerator with bilaterally opposed beams. Diseases treated included transitional cell carcinoma of the bladder, transitional cell carcinoma of the prostate, and anal sac apocrine gland adenocarcinoma. Four dose/fractionation schemes were used: 49.5 Gy in 3.3 Gy fractions, 54 Gy in 3.0 Gy fractions, 54 Gy in 2.7 Gy fractions, and 18 Gy intraoperative radiation therapy followed by 43 Gy external beam radiation therapy in 2.9 Gy fractions. Implantable chemotherapy in the form of an OPLA-Pt sponge was used in six dogs as a radiation potentiator. Colitis was the major late effect following pelvic irradiation, occurring in nine dogs (56%). Colitis was characterized as mild in three dogs, moderate in one dog, and severe in five dogs. Three of the dogs with severe effects suffered gastrointestinal perforation. All dogs with severe late effects received 3 or 3.3 Gy per fraction, and 80% received radiation potentiators. In the seven dogs that received 2.7 Gy or 2.9 Gy per fraction, late effects were classified as none (n = 5), mild colitis (n = 1), and moderate colitis (n = 1). Radiation therapy can be administered to the pelvic region with a minimal risk of late effects to the colon by giving smaller doses per fraction and avoiding systemic radiation potentiators.