Biomedical subjects

J W Gyves

Publications and source records attributed to J W Gyves.

25 records · Page 2Linked to original sources

PubMed1983

Improved regional selectivity of hepatic arterial mitomycin by starch microspheres.

Biodegradable starch microspheres, 40 microns in diameter, were administered through hepatic arterial catheters in 16 subjects with primary and metastatic liver tumors. These microspheres temporarily obstruct blood flow at the precapillary arteriole (microcirculation) level. Our study was undertaken to determine whether such occlusion would enhance hepatic deposition of, and thereby decrease systemic exposure to, simultaneously administered hepatic arterial mitomycin C (mito). When mito (10 mg/m2 over 1 min) was given with 90 X 10(6) microspheres (10 subjects), there was a 17% to 70% reduction in systemic mito exposure. When mito (10 mg/m2 over 1 min) was given with 36 X 10(6) microspheres (six subjects), there was a 15% to 60% reduction in systemic exposure, which may correlate with dose-dependent shunting (8% to 29%) through the liver to the lung (and hence to the systemic circulation), attributed to the starch microspheres. No life-threatening myelosuppression was noted; hepatic toxicity consisted of transient pain and elevation of liver enzymes.

Adult↗

PubMed1983

Hepatic arterial streptozocin: a clinical pharmacologic study in patients with liver tumors.

Hepatic arterial infusions of streptozocin (STZ) were compared with peripheral venous infusions administered for 3 h at a dose rate of 0.5 or 1.0 g/m2 . h in five patients with liver-predominant neoplastic disease. Peripheral venous plasma STZ levels were measured during and for 3 h after completion of all infusions. Steady-state was achieved at 2 h and the elimination half-life was 35-40 min, the total body clearance was 400 ml/min, and the volume of distribution of STZ was 20-22 liters in these patients. Comparison of steady-state drug levels demonstrated minimal hepatic extraction (mean 5%). Assuming a hepatic arterial blood flow of 100-200 ml/min with a total body clearance of 400 ml/min, hepatic arterial administration of STZ can be expected to result in a three- to sixfold greater exposure of tumor in the liver compared with the intravenous route. Toxicity was minimal and two patients had evidence of response.

Adult↗

PubMed1983

Quantitative hepatic arterial perfusion scintigraphy and starch microspheres in cancer chemotherapy.

Hepatic arterial infusion chemotherapy results in a higher concentration of drug delivered to the tumor with less systemic exposure than is possible with intravenous therapy. However, extrahepatic blood flow and/or shunting to the lung can impose a limitation. This study describes a quantitative method for calculating the extrahepatic component and monitoring its changes due to a new adjunctive therapy, degradable starch microspheres (DSM). DSM temporarily occlude the hepatic arterial circulation, thereby increasing the uptake of therapeutic drugs. Twenty patients with metastatic liver cancer underwent hepatic arterial perfusion scintigraphy (HAPS) using Tc-99m MAA to determine blood-flow distribution and to quantitate extrahepatic uptake. The percent shunt index (PSI) was determined at baseline and after each incremental dose of DSM. The baseline PSI ranged from 6-26% (mean 12.3 +/- 5.8 s.d.) and changed progressively after each injection of DSM/Tc-MAA suspension. The patterns of change in shunting are described. Quantitative HAPS provides a means of measuring the extrahepatic component, warns of potential side effects, and helps guide chemotherapeutic decisions.

Adult↗

PubMed1983

Clinical pharmacology of hepatic arterial chemotherapy.

The techniques now exist to deliver drug infusions reliably through the hepatic artery to infuse the entire liver and tumor within the liver. Drug selection for use in these systems should be rational and include agents with short half-lives (high total body clearance) and some evidence of activity against the tumor type in question. Hepatic extraction and metabolism of the drug will in turn decrease systemic exposure or allow more drug to be given per set amount of systemic exposure. The dose-limiting toxicity of appropriate drug programs may well be regional and not systemic. Further pharmacokinetic studies and controlled clinical trials are needed to evaluate existing regimens and to design new regimens. Future advances are likely to involve the combination of effective drugs and the use of therapeutic microspheres to improve selectivity based on tumor microcirculation.

Antineoplastic Agents↗

PubMed1982

New implantable continuous administration and bolus dose intracarotid drug delivery system for the treatment of malignant gliomas.

A totally implantable system for the continuous and bolus delivery of intra-arterial chemotherapeutic agents to patients with malignant gliomas is described. The system utilizes an Infusaid pump (Infusaid Corp., Sharon, Massachusetts), which discharges the drug directly into the internal carotid artery and is percutaneously refillable. This system has been utilized experimentally in primates and in the treatment of six patients with malignant gliomas. It seems that this system can be utilized safely as an experimental technique in the treatment of malignant gliomas.

Adult↗

PubMed1982

Perfusion scintigraphy (Tc-99m MAA) during surgery for placement of chemotherapy catheter in hepatic artery: concise communication.

In 17 patients receiving regional hepatic chemotherapy, Tc-99m macroaggregated albumin imaging was used to aid arterial catheter placement and to assess perfusion patterns. Intraoperative imaging with a portable gamma camera allowed immediate monitoring of hepatic and extrahepatic perfusion patterns and assisted catheter manipulation when necessary to achieve optimal flow distribution. In all 12 patients with standard hepatic arterial anatomy, complete perfusion of both lobes of the liver was achieved, although three of them required intraoperative catheter manipulation and repeat imaging after initial placement. The remaining five patients had aberrant hepatic arterial anatomy, and complete perfusion was more difficult to achieve; they exemplified the need for dual catheters, ligation of accessory hepatic branches, and repeated imaging.

Adenocarcinoma↗

PubMed1982

Totally implanted venous and arterial access system to replace external catheters in cancer treatment.

A totally implanted venous and arterial access system was tested in 30 cancer patients. The device, an injection port (Infuse-A-Port, Infusaid Corp., Sharon, Mass.), consisted of a 3.5 by 1.5 cm conical chamber with a self-sealing silicone rubber septum connected to a Silastic catheter. Ten patents had the injection port operatively placed for arterial access. A total of 39 bolus injections and 18 continuous infusions lasting an average 5.4 +/- 3.4 days were administered through the port. The total time of arterial access ranged from 70 to 370 days. No special program of heparinization was required to maintain patency. The injection port was used for central venous access in 20 patients. The first six patients had a small lumen catheter of 0.38 mm internal diameter, and five had occlusion between 142 and 447 days. Subsequently, 19 ports with a larger catheter lumen of 0.63 mm were used. These ports functioned for an average of 274 +/- 110 days (23 to 382 days). There were 380 single bolus injections and 64 continuous infusions. A variety of anticancer agents as well as whole blood, blood products, and antibiotics were administered with the device without difficulty. Patient acceptance was excellent.

Adult↗