Intraarterial infusions

Intraarterial infusion of microspheres containing adriamycin was used for the local treatment of breast cancer and recurrent breast cancer with liver metastases (123). A reduction in tumor size was noted when the microspheres were injected into the internal and lateral thoracic arteries for treatment of the primary tumor. However, hepatic artery injection for liver metastases resulted in improvement in only one of three patients treated. 

In reviewing intraarterial infusion of microencapsulated anticancer agents and its clinical applications, Nemoto (124) concluded that this mode of treatment can be used for a wide variety of tumors, providing remarkable therapeutic effects with minimal systemic toxicity. However, 25% of the treated tumors failed to respond, which was thought to be attributable to either inadequate catheterization, inadequate dose relative to tumor size, insufficient tumor vascularity, low drug sensitivity, or a combination of these factors. More carefully designed studies will be necessary before this technique is likely to meet with widespread acceptance. 

Olsson AG, Carlson LA. Clinical, hemodynamic and metabolic effects of intraarterial infusions of prostaglandin El in patients with peripheral vascular disease. Adv Prostaglandin Thromboxane Res 1976 1 429-32. 

FIGURE 4 Inhibitory effect of S-nitroso-N-acetylpenicillamine (SNAP) on vasodilator responses to acetylcholine. Solid columns represent control responses to intraarterial (i.a.) bolus injections of acetylcholine in the doses indicated. Hatched columns represent identical injections of acetylcholine during concurrent intraarterial infusion of SNAP (100 jug/kg/min) and phenylephrine (the infusion rate of phenylephrine was adjusted to keep the baseline perfusion pressure constant). The open column represents the intraarterial bolus injection of 1 /Ag of acetylcholine 15 min after the SNAP-phenylephrine infusion was discontinued. All experiments were conducted in rabbits under conditions of constant blood flow. 0, No Responses , P < 0.05. Data represent absolute changes in hindquarters perfusion pressure (in mm Hg), expressed as means se of one determination from four to seven animals. 

Ogawa A, Mori E, Minematsu K et al. Randomized trial of intraarterial infusion of urokinase within 6 hours of middle cerebral artery stroke the middle cerebral artery embolism local fibrinolytic intervention trial (MELT) Japan. Stroke. 2007 38 2633-2639... 

There have been three types of studies conducted in the IPPSF toxicology, percutaneous absorption (including biotransformation and pharmacokinetic modeling), and cutaneous drug distribution (drug administered by intraarterial infusion). The first two are discussed in this chapter. 

Fortin D, Desjardins A, Benko A, Niyonsega T, Boudrias M. Enhanced chemotherapy delivery by intraarterial infusion and blood-brain barrier disruption in malignant brain tumors the Sherbrooke experience. Cancer 2005 103 2606-2615. 

Lau WY, Ho S, Leung TW et al (1998) Selective internal radiation therapy for nonresectable hepatocellular carcinoma with intraarterial infusion of 90yttrium microspheres. Int J Radiat Oncol Biol Phys 40 583-592... 

Yu et al. [58] reported on 49 patients who underwent 78 administrations of SIR-Spheres via intraarterial infusion in the left or right hepatic artery. Of these patients, 26 had a diagnosis of colorectal... 

Combinatorial Y and TACE presents an interesting opportunity to assess the cumulative effect of these modalities in effecting tumor kill. Intraarterial infusion of Y in an aerobic environment (non-stasis) could be followed by TACE after the radioactive effect diminishes to sub-therapeutic levels (approximately 2 weeks post Y treatment). TACE administration with cytotoxic tumor exposure in a hypoxic environment would then address any viable (radioresistant) cells that remained. 

A Step Towards Supraconservative Surgery 103 Interventional Procedures for the Locoregional Treatment of Breast Cancer 105 Percutaneous Imaging-Guided Tumor Ablation 105 Intraarterial Infusion Chemotherapy 106 References 106... 

Murakami M, Kuroda Y, Nishimura S, Sano A, Okamoto Y, Tanigu Nakajima T, Kobashi Y, Matsusue S (2001) Intraarterial infusion chemotherapy and radiotherapy with or without surgery for patient with locally advanced or recurrent breast cancer. Am J Clin Oncol 24 185 191... 

ChemoemboKzation is a technique that was proposed by Kato et al. (1981) in which intraarterial infusion... 

Biologic Response However, monitoring the size of the tumor is often impractical for several types of minimally invasive regional therapy such as embolization, intraarterial infusion, chemoembolization, or tumor... 

LA. Infusion For the treatment of colorectal metastases to liver, systemic 5- fluorouracil (5FU) yielded a 20% response rate. FUDR infused through a catheter placed surgically or percutaneously into the hepatic artery, had response rates ranging from 32% to 88% depending upon the criteria utilized. Despite effective control of hepatic disease, extrahepatic metastases were usually the major cause of death. At MDACC, the intraarterial infusion of FUDR (100 mg/m /day-h5) and mitomycin C (10 mg/m ) yielded a response rate of 61% in previously untreated patients, and 45% in patients who failed to respond to previous intravenous 5FU. A response rate of 52% was found with the intraarterial infusion of FUDR and cisplatin (100 mg/m ). The median survival time for the responders was 16 months. 

Chemoembolization Chemoembolization regimens for metastatic leiomyosarcoma have included cis-platin (150 mg) and Ivalon, 150-250 pm, (150 mg) followed by a 2-h intraarterial infusion of vinblastine (10 mg/m ) at 4-week intervals (Mavligit et al. 1988). The response rate was 70% and lasted 4-19 months (median 9 months). Usually, a response greater than PR was observed. 

Fig. 9.9a, h. Breast carcinoma with hepatic metastases. Hepatic artery infusion, a Abdominal computed tomography (CT). Multiple hilohar hepatic metastases prior to intraarterial infusion. The patient had failed previous intravenous therapy, b Abdominal CT, 7 months later, demonstrated an excellent response after treatment with courses of hepatic artery infusion with Taxol (Bristol Myers Squibb, Princeton, NJ)... 

LA. Infusion. In 1961, Byron et al. reported on their experience with intraarterial infusion of ten patients with bladder cancer who failed to respond. The use of intraarterial chemotherapy was reported by Nevin and Hoffman (1975), who surgically implanted catheters into each internal iliac artery. 5-Fluoroura-cil was infused for 10 days and then every other week for 3 months when it was given as an adjunct to chemotherapy. Regression of local disease was seen in six of ten patients. A mean survival time of 25 months was noted in the complete responders. Fourteen of 28 patients responded but, because of the dosage and myelosuppression, local irritation was significant. 

A group of 45 patients studied by Mokarim et aL (1997) with muscle invasion of the bladder was treated with transcatheter intraarterial infusion of cisplatin (70 mg/m ) and doxorubicin (30 mg/m ) delivered over 30-40 min for an average of three courses at 4-week intervals. A complete response was obtained in 20 patients (44%), partial response in 17 (38%), and stable disease in six (13%). The overall response rate was 82% at a median follow up of 36 months. Mokarim et al. (1997) also treated 35 patients with muscle invasive bladder cancer Stages T2-T4 NoMo with two courses of intraarterial cisplatin (70 mg/m ) and doxorubicin (30 mg/m ) over 30-40 min at 3-week intervals followed by irradiation from a finear accelerator (10 MeV) at 40 Gy over 4 weeks. In the presence... 

Embolization Hemorrhage from genitourinary neoplasms have been treated successfully by the intraarterial infusion of chemotherapy if the bleeding is chronic. 

The rationale for preoperative intraarterial infusion of osteosarcoma is to control the local primary tumor,... 

An experimental study by Wang et al. (2001) utilizing isolated limb perfusion demonstrated that single-pass dialysis can remove 85%-95% of cisplatin, reduce systemic toxicity, and permit survival of experimental animals. The clinical use of isolated intraarterial infusion with dialysis in patients with inoperable osteosarcoma showed that patients were able to tolerate doses of cisplatin that would otherwise be intolerable by systemic intravenous infusion. 

Chuang VP, Wallace S (1980) Hepatic arterial redistribution for intraarterial infusion of hepatic neoplasms. Radiology 135 295-299... 

Taniguchi H, Takahashi T, Yamaguchi T, Sawai K (1989) Intraarterial infusion chemotherapy for metastatic liver tumors using multiple anti-cancer agents suspended in a lipid contrast medium. Cancer 64 2001-2006... 

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