Background: Between 1991 and 1997 sixty-seven patients with non-resectable hepatoma were treated with hepatic artery infusions (HAI) of cisplatinum. Patients were divided into groups for analysis based on alpha-fetoprotein elevation (AFP+) or no elevation (AFP-), hepatitis B/C status, the presence or absence of extra-hepatic metastases and primary treatment at our facility or initial therapy elsewhere. Methods: Forty-four patients received an initial course of 21-24 Gy whole liver external radiation with cisplatinum 50 mg/m.sup.2 IV on days 1 and 8 of radiation. Twenty-three patients did not receive external radiation and received HAI cisplatinum only. All patients were then treated with HAI cisplatinum at 50 mg/m.sup.2 on a monthly basis. The rationale for the advantage to HAI cisplatinum was evaluated by giving a tracer dose of radioactive .sup.195m cisplatinum for quantitative determinations by the intra-arterial route in six patients. Results: A 50% overall response rate was seen, as judged by a 50% reduction in tumor diameter or a 50% reduction in AFP titer. Monthly HAI cisplatinum at 50 mg/m.sup.2 was well tolerated and could be repeated indefinitely without significant toxicity. Median survival for primarily treated non-resectable hepatomas AFP(+) and AFP(-) was 12 months and 17.5 months, respectively. Statistical analysis of all patients AFP(+) versus AFP(-) revealed a log rank statistical difference in survival of P=0.007. For patients with hepatitis B or C median survival was 10.7 months regardless of AFP status. Radioactive cisplatinum given by hepatic arterial infusion provided 34-55% tumor uptake of cisplatinum. Conclusions: Intra-arterial delivery of 50 mg/m.sup.2 cisplatinum on a monthly basis is a well-tolerated regimen for patients with non-resectable hepatoma. These data suggest a baseline chemotherapy regimen against which randomized trials could be evaluated. Further, the selective uptake of cisplatinum delivered intra-arterially suggests other selective intra-arterial protocols would be of use in regional cancers treated with cisplatinum. Keywords: Hepatoma, hepatocellular, carcinoma, cisplatin, cisplatinum, .sup.195m cisplatinum, radioisotopes, intra-arterial.
This application claims the benefit of the filing date of provisional application Ser. No. 60/078,818 filed on Mar. 20, 1998, the entire disclosure of which is incorporated by reference herein.
A method of preparing high-specific-activity .sup.195m Pt includes the steps of: exposing .sup.193 Ir to a flux of neutrons sufficient to convert a portion of the .sup.193 Ir to .sup.195m Pt to form an irradiated material; dissolving the irradiated material to form an intermediate solution comprising Ir and Pt; and separating the Pt from the Ir by cation exchange chromatography to produce .sup.195m Pt.
A new composition of matter includes .sup.195m Pt characterized by a specific activity of at least 30 mCi/mg Pt, generally made by method that includes the steps of: exposing .sup.193 Ir to a flux of neutrons sufficient to convert a portion of the .sup.193 Ir to .sup.195m Pt to form an irradiated material; dissolving the irradiated material to form an intermediate solution comprising Ir and Pt; and separating the Pt from the Ir by cation exchange chromatography to produce .sup.195m Pt.
There is provided a method of synthesis of a radiolabelled platinum chemotherapeutic agent comprising the steps of: converting a metal halide to a radiolabelled platinum halide wherein the radiolabel is a radioisotope of Pt; and synthesizing the radiolabelled platinum chemotherapeutic agent from the radiolabelled platinum halide.
