Search PubMed⌕ Search

Biomedical subjects

A G Wile

Publications and source records attributed to A G Wile.

At least 37 records · Page 2Linked to original sources
PubMed1987

The pharmacology of hepatic regional administration of cisplatin in a rabbit model.

The pharmacology of hepatic regional administration of CisplatinR (DDP) was examined in a rabbit model. Routes and modes of administration were: IV, hepatic arterial infusion (HAI), HAI with stopflow, HAI with microembolic material [collagen for embolization (CFE)], and portal vein (PV). DDP was rapidly administered, blood samples were drawn over 45 minutes, and hepatic tissue was obtained. Filterable plasma DDP levels were measured by HPLC. Hepatic DDP levels were determined by atomic absorption spectroscopy. All modes of regional administration yielded significantly higher hepatic DDP levels when compared to tissue levels following IV administration. Only the PV and HACFE routes resulted in significantly less systemic drug exposure (AUC) when compared to IV administration. These data indicate a relative pharmacologic advantage of 1.8 for HAI, 3.4 for PV, 1.8 for HAI stopflow, and 4.3 for HACFE compared to IV DDP administration. This pre-clinical study demonstrates substantial pharmacologic advantage for PV and HACFE routes of DDP administration and suggests that clinical trials based on this information be considered.

Animals↗
PubMed1986

Good tolerance to high-dose hepatic arterial infusion therapy.

A pilot study was designed to evaluate the efficacy of high-dose FUDR administered through the hepatic artery for the treatment of cancer involving the liver. Three dose schedules were used beginning with a dose of 0.5 mg FUDR/kg/day for 2 weeks followed by normal saline infusion for 2 weeks (schedule A). Elevation of serum bilirubin was the sole indication to deescalate to schedule B (0.3 mg FUDR/kg/day for two weeks followed by saline infusion for 4 weeks). Tolerance to this schedule escalated the patient to schedule C (0.5 mg FUDR/kg/day for 2 weeks followed by normal saline infusion for 4 weeks). Eighteen patients were treated, sixteen with metastatic colon cancer, one with metastatic leiomyosarcoma, and one with hepatoma. The patient with hepatoma developed progressive disease after one cycle of therapy. Of the 17 patients with metastatic cancer only 5 patients failed therapy yielding a 70% response rate. High-dose FUDR was well tolerated with only six patients requiring deescalation to schedule B. Elevation of alkaline phosphatase and glutamic oxaloacetic transaminase was universal. Two patients developed peptic ulceration. Sclerosing cholangitis was not observed. We conclude that high-dose FUDR administered through the hepatic artery is as safe as conventional dose infusion therapy but probably not more effective. The safety of high-dose FUDR infusion therapy suggests that sclerosing cholangitis is association with hepatic arterial infusion therapy is not related to the FUDR dose.

Drug Administration Schedule↗
PubMed1986

Technique for placement of an implantable venous access system.

Increasingly complex programs of cancer chemotherapy have necessitated a system of reliable venous access that is relatively free of infectious complications. These criteria are met by the Porta-Cath, a totally implantable system consisting of an injection port and Silastic catheter. A technique for implantation of this device has been presented. It focuses on patient safety and comfort, ease of placement, and minimization of time and expense in the operating room.

Catheterization↗
PubMed1986

Hematoporphyrin phototherapy of cancer.

Hematoporphyrin phototherapy of cancer is a new modality for cancer diagnosis and treatment that is currently undergoing clinical trials worldwide. A variety of tumors have been studied, e.g., breast (mostly recurrent skin), lung, bladder, eye, head and neck, gynecological and brain. The most success to date has been with lung and the gynecological tract. Cell and animal studies are being conducted to elucidate the basic photobiological mechanisms involved, as well as the histopathological events associated with tumor destruction. Although major questions remain to be resolved, hematoporphyrin phototherapy is an exciting new therapeutic modality for the treatment of cancer, especially in sites where the unique features of lasers and fiber optics are advantageous.

Breast Neoplasms↗
PubMed1986

Pharmacokinetics of 5-fluorouracil in rabbits in experimental regional chemotherapy.

The goal of this study was to identify the mode(s) of regional administration of 5-fluorouracil (5-FUra) with the greatest pharmacological advantage in an animal model. Parameters examined were the amount of systemic exposure to 5-FUra and plasma and tissue levels of 5-FUra. Anesthetized New Zealand white rabbits bearing a VX-2 carcinoma in the thigh received 5-FUra (20 mg/kg body weight) by the following routes: i.v., intraarterial (i.a.), i.a. with stopflow, i.a. with outflow occlusion, and isolation perfusion (IP). Serial venous blood samples were obtained prior to and after drug administration for a total of 45 min. A similar sampling of the perfusion circuit was conducted in those animals undergoing IP. At the end of the sampling period tumor and adjacent normal muscle were obtained. Plasma and tissue levels of 5-FUra were determined by a high pressure liquid chromatographic method. It was observed that systemic exposure to 5-FUra was identical for the i.v., i.a., i.a. with stopflow, and i.a. with outflow occlusion groups. Systemic exposure to 5-FUra in the IP group was only 0.30 of that observed for the i.a. group. Tissue 5-FUra levels in the i.v., i.a., and i.a. with stopflow groups were low and comparable to one another. Tissue levels of the 5-FUra were significantly higher in the i.a. with outflow occlusion and IP groups. We conclude that only selected forms of regional administration of 5-FUra offer pharmacological advantage when compared to systemic administration.

Animals↗
PubMed1985

The use of lipid emulsion as an intravesical medium to disperse light in the potential treatment of bladder tumors.

An obstacle to satisfactory treatment of early bladder cancer with hematoporphyrin derivative-photoradiation therapy is nonuniform illumination of the bladder mucosa. This study was done to determine the characteristics and attenuation of laser light passing through the dispersion medium. Bladder simulation was achieved with the use of 5 different sizes of round-bottom flasks. Intralipid was the dispersion medium. For each flask, 6 different concentrations of the dispersion medium were used. An Argon ion laser was used to stimulate a dye laser at 630 nm. The laser was directed toward the center of the flasks via a fiberoptic cable and energy concentration at 7 different angles was measured. We concluded that the optimal medium was a 1:100 dilution of Intralipid with water, which produced an almost uniform dispersion of light on the walls of the flask. There is a linear correlation between power as measured at the fiber tip and the amount of radiation detected on the walls of the flasks. After determining optimal concentration of medium, we calculated the amount of time needed for a desired energy (Joules/cm.2) to treat a tumor. This calculation was based on the size of the bladder and the power as measured at the fiber tip. The results indicate it is possible to treat the entire mucosa of the bladder with a uniform dose of photoradiation energy.

Fat Emulsions, Intravenous↗
PubMed1985

Pharmacokinetics of 5-fluorouracil during hyperthermic pelvic isolation-perfusion.

The pharmacokinetics of 5-fluorouracil (5-FU) injected into a surgically isolated pelvic circuit during hyperthermic perfusion was studied in five patients with local recurrence of anorectal cancer. 5-FU doses ranged from 11 to 23 mg/kg. The geometric mean ratio of peak plasma 5-FU in the isolated to systemic circuits was 10, the ratio at the end of the 45-minute perfusion was 12.5. The mean half-life of 5-FU in the isolated circuit was 18.5 minutes. Total drug exposure for the isolated circuit was 7.8-fold greater than for the systemic compartment. These results demonstrate a large pharmacologic advantage for the use of the isolation-perfusion technique.

Adenocarcinoma↗
PubMed1984

Laser photoradiation therapy of cancer: an update of the experience at the University of California, Irvine.

This update of the experience at the University of California at Irvine with laser photoradiation therapy (PRT) encompasses the period between May 1981 and June 1983. The results of treatment of 77 patients are reported (head and neck, 39; breast, 33; and lung 5). Head and neck cancer patients received treatment to 114 sites with a complete response (CR) in 28, partial response (PR) in 42, stable disease (SD) in three, and no response (NR) in 34, and an undetermined response in seven. Breast cancer patients were treated in 395 sites with CR in 222, PR in 74, SD in one, NR in 92, and undetermined response in six. The lung cancer patients in this series responded poorly, if at all. In addition to the above patient trials, we have investigated the interaction of laser hematoporphyrin derivative (HPD)-PRT with a chemotherapeutic agent, Cisplatin, against an experimental tumor (RIF-1) in an animal model. We have been unable to demonstrate an additive effect of laser HPD-PRT at total light doses of 25 J/cm2 and 75 J/cm2 with Cisplatin at a dose of 7 mg/kg. However, no additional toxicity was observed in combination therapy, suggesting that sequential application of laser HPD-PRT and Cisplatin may be safely employed in clinical situations. Another area of investigation has been the evaluation of the light-scattering characteristics of a lipid emulsion designed for laser HPD-PRT of bladder tumors. We have demonstrated that it is feasible to gain uniform illumination of the bladder surface with the use of this light-dispersing medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Evaluation of visual acuity during laser photoradiation therapy of cancer.

Visual function for ten patients undergoing HPD-PRT was tested using 1) the Graham Field Eye Chart for distance vision, 2) pseudo-isochromatic plates for color vision, and 3) Amsler grid for changes in macular function. Whereas some increases and decreases in ocular function were observed, no clear patterns or changes of significance were observed.

Adult↗
PubMed1984

Laser photoradiation therapy of cancer: possible role of hyperthermia.

Two patients were treated at 20 different tumor sites by hematoporphyrin derivative (HPD) photoradiation therapy (PRT). An infrared detector was used to record changes in surface temperature during laser exposure. A temperature rise of up to 4.9 degrees C was recorded for a total energy of 15-30 J/cm2 and less than 150 mW/cm2. For 508 mW/cm2 and 15-20 J/cm2 a temperature rise of 7.0 degrees C was detected. The results suggest a possible role of hyperthermia in HPD-PRT.

Body Temperature↗
PubMed1984

Soluble suppressor factors elaborated in experimental malignant ascites.

Soluble suppressor factors in the sera of cancer patients inhibit lectin-stimulated lymphocyte proliferation. These factors, derived from human material, preclude easy corroboration by other investigators. To gain a general understanding of soluble suppressor factors and to avoid the necessary restrictions of human experimentation, an animal model was devised. Sprague-Dawley rats were injected ip with the Walker 256 carcinoma. The resultant ascites proved to be a stable, reproducible source of soluble suppressor factors. Ascites inhibited phytohemagglutinin (PHA)-induced blastogenesis of normal splenocytes by 98%. The possibility of a toxic effect was eliminated by vital staining of splenocytes and by examination in a specific lymphotoxin assay. Suppressor activity persisted after heating at 100 degrees C for 40 min. Extraction by lipid solvents revealed that the bulk of suppressor activity resides in the lipid phase. The active fraction of heat-treated ascites passed through an Amicon PM-10 filter. Thin-layer chromatography revealed the presence of prostaglandins E2 and F2 alpha. Tissue culture supernatants from short-term cultures derived from tumor-bearing animals revealed suppressor activity from thymus, spleen, and liver cultures (97, 91, and 71%, respectively). No suppressor activity was detected in cultures of cancer cells. This study has demonstrated in this animal model that prostaglandins play a major role in suppression of lectin-induced blastogenesis. All suppressor factors appear to be host derived. An understanding of the mechanism of release of these suppressor substances may open new avenues in the immunotherapy of cancer.

Animals↗
PubMed1984

Photoradiation therapy of head and neck cancer.

We have embarked upon a pilot study of photoradiation therapy (PRT) in the treatment of persistent or recurrent cancer of the head and neck, utilizing the photosensitizing agent, hematoporphyrin derivative (HPD). This treatment is based upon selective concentration of HPD within malignant tissue, with resultant necrosis upon illumination with light of the appropriate wavelength (640 nm). Patients entered in this trial have failed all forms of conventional therapy. Twenty-one patients with local recurrence were treated. Sites of recurrence were: tongue (9); nasopharynx (3); floor of mouth (2); soft palate (2); oropharynx (1); buccal mucosa (1); maxilla (1); larynx (1); and basal cell nevus (1). There were six complete responses and twelve partial responses (greater than 50% reduction). These responses are clinically significant, with some complete responses lasting over 1 year after a single course of therapy. Ten patients with cutaneous metastases from head and neck primary tumors were also treated. There were two complete responses and three partial responses. However, these patients rapidly developed new tumors in areas adjacent to those previously treated. Less than complete responses could be augmented by repeated applications of this technique. The success of this pilot study combined with the accessibility of head and neck primaries suggest that there should be a clinical trial of HPD-PRT in early mucosal cancer of the head and neck region.

Bronchoscopy↗
PubMed1984

Photoradiation therapy of head and neck cancer.

We have embarked upon a pilot study of photoradiation therapy (PRT) in the treatment of persistent or recurrent cancer of the head and neck utilizing the photosensitizing agent hematoporphyrin derivative (HPD). This treatment is based upon selective concentration of HPD within malignant tissue with resultant necrosis upon illumination with light of the appropriate wave length (630 nm). Patients entered in this trial have failed all forms of conventional therapy. Twenty-one patients with local recurrence were treated. Sites of recurrence were: tongue (9), nasopharynx (3), floor of mouth (2), soft palate (2), oropharynx (1), buccal mucosa (1), maxilla (1), larynx (1), basal cell nevus (1). There were six complete responses and twelve partial responses (greater than 50% reduction). These responses are clinically significant with some complete responses lasting over one year after a single course of therapy. Ten patients with cutaneous metastases from head and neck primary tumors were also treated. There were two complete responses and three partial responses. However, these patients rapidly developed new tumors in areas adjacent to those previously treated. Less than complete responses could be augmented by repeated applications of this technique. The success of this pilot study combined with the accessibility of head and neck primaries suggest that HPD-PRT should be given a clinical trial in early mucosal cancer of the head and neck region.

Antineoplastic Agents↗
PubMed1983

Enhanced tumor growth in experimental whole body hyperthermia.

The purpose of this study was to investigate the interaction of heat and chemotherapy in experimental whole body hyperthermia (WBH). A vascular technique of extracorporeal perfusion was employed to rapidly elevate body temperature in rabbits carrying the transplantable VX-2 carcinoma. Hyperthermia (greater than 41 degrees C) was achieved in a mean time of 28 minutes. Tumor-bearing rabbits receiving WBH alone exhibited poor mean survival (14 days) relative to untreated tumor-bearing animals (32 days) and the group receiving IV Cis-platinum alone (50 days) (NS, p less than .05 respectively). WBH with Cis-platinum was intermediate in terms of mean survival (30 days, NS) between the WBH alone and Cis-platinum alone groups. In this experimental model we have determined WBH to be a detrimental form of cancer therapy. Its action appears to enhance tumor proliferation, resulting in rapid animal demise. In light of these findings a reevaluation of clinical WBH may be warranted.

Animals↗
PubMed1983

Hepatic artery-biliary fistula. An unusual complication of infusion therapy.

This report describes a patient with carcinoid metastatic to the liver in whom a hepatic artery catheter was placed for infusion therapy. This resulted in a previously unreported complication of a hepatic artery-biliary fistula. The clinical presentation of this complication and mode of management are described. The etiologic factors responsible for this complication are discussed. It is speculated that as more aggressive therapy for hepatic metastases is undertaken, this potential complication will be seen more frequently.

Antineoplastic Agents↗
PubMed1983

Experimental hyperthermic isolation-perfusion using cis-diamminedichloroplatinum(II).

The intent of this study was to determine whether or not local control and/or cure of rabbits bearing the VX-2 carcinoma could be achieved with regional hyperthermia and chemotherapy. A model of isolation-perfusion used cis-diamminedichloroplatinum(II) (DDP). Five different experimental groups were studied, each group receiving progressively smaller tumor inocula and shorter treatment intervals. Although local control and cure improved as the tumor inocula became smaller and treatment interval became shorter, there was no benefit demonstrated when compared to sham-operated animals. DDP appeared to be well tolerated in animals perfused as normothermic temperatures. However, animals perfused at hyperthermic temperature with DDP experienced necrosis of normal as well as neoplastic tissue, resulting in early demise of the animal. This final observation suggests that the amount of DDP utilized in clinical isolation-perfusion should be approached with caution.

Animals↗