Phase I and pharmacokinetic (PK) study of MAG-CPT (PNU 166148): a polymeric derivative of camptothecin (CPT).

Polymeric cytotoxic conjugates are being developed with the aim of preferential delivery of the anticancer agent to tumour. MAG-CPT comprises the topoisomerase I inhibitor camptothecin linked to a water-soluble polymeric backbone methacryloylglycynamide (average molecular weight 18 kDa, 10% CPT by weight). It was administered as a 30-min infusion once every 4 weeks to patients with advanced solid malignancies. The objectives of our study were to determine the maximum tolerated dose, dose-limiting toxicities, and the plasma and urine pharmacokinetics of MAG-CPT, and to document responses to this treatment. The starting dose was 30 mg m(-2) (dose expressed as mg equivalent camptothecin). In total, 23 patients received 47 courses at six dose levels, with a maximum dose of 240 mg m(-2). Dose-limiting toxicities were myelosuppression, neutropaenic sepsis, and diarrhoea. One patient died after cycle 1 MAG-CPT at the maximum dose. The maximum tolerated dose and dose recommended for further clinical study was 200 mg m(-2). The half-lives of both MAG-CPT and released CPT were prolonged (>6 days) and measurable levels of MAG-CPT were retrieved from plasma and urine 4 weeks after treatment. However, subsequent pharmacodynamic studies of this agent have led to its withdrawal from clinical development.

Photodynamic therapy of facial squamous cell carcinoma in cats using a new photosensitizer.

BACKGROUND AND OBJECTIVE: Photodynamic therapy has been shown to be an effective treatment modality for surface-oriented neoplasms of the skin, respiratory, gastrointestinal, and urogenital systems. The purpose of this study was to assess the safety and efficacy of photodynamic therapy using a new photosensitizer in the treatment of squamous cell carcinomas of the feline facial skin. STUDY DESIGN/MATERIALS AND METHODS: Cats with naturally occurring squamous cell carcinomas of the facial skin were entered into the study. Tumors were staged using a modification of the World Health Organization (WHO) system for classification of feline tumors of epidermal origin. Photodynamic therapy was delivered to the tumors using an argon-pumped dye laser 24 hours after the administration of the photosensitizer pyropheophorbide-alpha-hexyl-ether (HPPH-23). Following treatment, tumors were evaluated for complete response rates and local control durations. RESULTS: Fifteen tumors were staged T1a (< 1.5 cm diameter, noninvasive), 18 T1b (< 1.5 cm, invasive), and 28 T2B (> 1.5 cm, invasive). Complete response rates as well as local control durations were significantly (P < 0.05) related to stage. Complete response was achieved in 100% of T1a tumors, 56% of T1b tumors, and 18% of T2b tumors. One-year local control rates were 100% for T1a tumors and 53% for T1b tumors; overall 1-year local control rate for all treated tumors was 62%. Clinical, hematological, and biochemical evidence of toxicity was not seen in any cat following drug administration. However, morbidity was observed following treatment of large, invasive tumors of the nasal plane. CONCLUSION: Photodynamic therapy with the photosensitizer HPPH-23 was safe and effective in treating early stage squamous cell carcinomas of the feline nasal plane and facial skin. However, toxicity was encountered following treatment of large neoplasms.

Photodynamic therapy in veterinary medicine: current status and implications for applications in human disease.

The historical development and published veterinary applications of photodynamic therapy are reviewed. Potential animal models, using naturally-occurring diseases in veterinary patients, for the future development of photodynamic therapy are described.

Oncologic applications of endoscopy.

Endoscopic examinations provide a valuable, noninvasive adjunct in the diagnosis and staging of many neoplastic disorders (Table 1). Additionally, the clinical applications of endoscopic-guided laser or photodynamic therapy have yet to be investigated thoroughly in companion animals. Endoscopy does not eliminate the need for other diagnostics, rather it should be considered complementary to more "traditional" procedures such as radiography, surgery, and ultrasonography.

Effect of acepromazine, diazepam, fentanyl-droperidol, and oxymorphone on gastroesophageal sphincter pressure in healthy dogs.

Treatment of healthy dogs with 4 commonly used psychotropic or analgesic agents significantly decreased resting gastroesophageal sphincter pressure (GESP). Acepromazine decreased GESP by 35% (P = 0.02); oxymorphone decreased GESP by 38% (P less than 0.005); diazepam decreased GESP by 42% (P = 0.005); and fentanyl-droperidol decreased GESP by 40% (P = 0.03). Therefore, esophageal manometric evaluation of gastroesophageal sphincter function should not be preceded by administration of these drugs.

Cholecystography and cholecystoduodenostomy in the diagnosis and treatment of bile duct obstruction in a dog.

A common bile duct obstruction was documented in a dog, by performing cholecystography haparoscopic visualization facilitated performance of the cholecystography. Target cells were a consistent hematologic finding. Cholecystoduodenostomy, an easily performed surgical technique, allowed for restoration of bile flow and resolution of clinical signs.

Hepatic neoplasia.

The clinicopathologic features of hepatic neoplasms such as hepatocellular adenomas, hepatocellular carcinomas, bile duct carcinomas, and hepatic carcinoids are presented. The authors also discuss the diagnostic and therapeutic approaches to hepatic neoplasia.