CONCURRENT IRRADIATION AND INTRATUMORAL CHEMOTHERAPY WITH CISPLATIN - A PILOT-STUDY IN DOGS WITH SPONTANEOUS TUMORS

Purpose: A preliminary study was undertaken to determine whether the addition of a collagen gel in the formulation of cisplatin for intratumoral administration of cisplatin affected platinum plasma concentrations. A second study was undertaken to determine the local effects of intratumoral administration of cisplatin mixed with collagen given concurrently with irradiation. Methods and Materials: Twelve dogs with advanced stage tumors were administered a dose of 0.25 mg of cisplatin per kg of body weight intratumorally with or without collagen using a two-period crossover design. Twelve additional dogs received concurrent irradiation (48 Gy) delivered in 12 fractions over 4 weeks and intratumoral cisplatin chemotherapy given the first day of each week at a dose of 0.5 mg of cisplatin per cm(3) of tissue. Results: The cumulative cisplatin plasma concentrations varied over time from dog to dog, but the use of collagen in the-formulation significantly reduced the systemic exposure of cisplatin. For the dogs given intratumoral cisplatin and irradiation, complete responses were observed in 10 dogs. Seven dogs had local recurrence. One dog had tumor recurrence in the radiochemotherapy field and six dogs had recurrence at the margin of the radiochemotherapy field, but within the irradiation field. Normal tissue reactions were similar in the radiochemotherapy field and in the margin treated with radiation only. Cumulative effect of repeated intratumoral administration on plasma concentration of cisplatin was not observed. Conclusions: These findings provide support for an extended investigation of this combined regimen. The lack of systemic toxicity associated with intratumoral administration of cisplatin mixed with collagen may allow a safe clinical evaluation of the interaction between cisplatin and radiation.