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Biomedical subjects

J M Daly

Publications and source records attributed to J M Daly.

At least 163 records · Page 9Linked to original sources
PubMed1987

Perfusion of colorectal hepatic metastases. Relative distribution of flow from the hepatic artery and portal vein.

The importance of portal circulation in the delivery of drugs and nutrients to colorectal hepatic metastases is controversial. Using 13N (nitrogen 13) amino acids and ammonia with dynamic gamma camera imaging, we demonstrate, for the first time in human beings, a quantitative advantage of hepatic artery compared with portal vein infusion. Eleven patients were studied by hepatic artery injection, five patients were studied by portal vein injection, and two patients had injections through both routes. Data collected from the liver for 10 minutes after rapid bolus injection of 13N L-glutamate, L-glutamine, or ammonia were compared with 99mTc (technetium) macroaggregated albumin (MAA) images produced after injection through the hepatic artery or portal vein at the same session. Tumor regions defined from 99mTc sulfur colloid scans were compared with nearby liver areas of similar thickness. For the 13N compounds, the area-normalized count rate at first pass maximum (Qmax) and the tissue extraction efficiency were computed. The tumor/liver Qmax ratios for MAA and 13N compounds were highly correlated. Both tumor and liver extracted more than 70% of the nitrogenous compounds. The tumor/liver Qmax ratios reflect the relative delivery of injected tracer per unit volume of tissue. After hepatic artery injection the Qmax ratio was 1.03 +/- 0.33 (mean +/- SD), significantly exceeding the Qmax ratio of 0.50 +/- 0.34 after portal vein injection (P less than 0.003). Therefore, more than twice as much of a nutrient substrate is delivered per volume of tumor relative to liver by the hepatic artery as by the portal vein; the high extraction efficiency demonstrates that the hepatic artery flow is nutritive; and the delivery of substance in solution (such as nutrients or drugs) to tumor and liver tissue correlates with the distribution of colloids such as macroaggregated albumin after hepatic arterial and portal venous injection.

Adult↗
PubMed1987

Alteration of methotrexate metabolism in rats by administration of an elemental liquid diet. II. Reduced toxicity and improved survival using cholestyramine.

The administration of an elemental, chemically defined liquid diet to rats significantly enhanced gastrointestinal toxicity associated with methotrexate administration compared with rats fed a regular chow diet. Chemotherapy induced enteritis is potentially enhanced by the abrasive effect of bile acids on the susceptible cells of the small bowel mucosa. This study evaluated the interactions of methotrexate and cholestyramine in vitro. An additional goal was to evaluate the effects of cholestyramine on animal survival and drug pharmacokinetics in rats given an elemental, chemically defined liquid diet. In vitro binding of cholestyramine to methotrexate increased in a linear fashion at varying concentrations of both drugs in phosphate buffer solution (r greater than 0.84, P less than 0.001) and in bile which was not influenced by pH (range 5-8). The addition of cholestyramine to an elemental liquid diet significantly improved survival following methotrexate administration (20 mg/kg IP bolus) compared with rats fed an elemental liquid diet alone (P less than 0.02). Both elemental liquid diets, either with or without cholestyramine, delayed serum and biliary clearance of methotrexate up to 72 hours compared with rats fed a regular chow diet. However, rats fed an elemental liquid diet with added cholestyramine had significantly lower levels of methotrexate in serum from the systemic and portal venous circulation at 48 hours (P less than 0.03) and in bile at 48 (P less than 0.02) and 72 hours (P less than 0.05) following methotrexate administration. The addition of cholestyramine to an elemental liquid diet improves survival and reduces gastrointestinal toxicity following methotrexate administration, by binding methotrexate in bile and reducing the delay in systemic clearance of the drug. By binding to intraluminal bile acids, cholestyramine may also have a locally protective effect on the mucosal cells of the small intestine following methotrexate administration. Cholestyramine may be of clinical benefit in patients receiving high-dose methotrexate regimens as an adjunct to leucovorin rescue.

Animals↗
PubMed1987

Alteration of methotrexate metabolism in rats by administration of an elemental liquid diet. I. Changes in drug enterohepatic circulation.

Severe enteritis and death consistently occur within 150 hours of a single intraperitoneal dose of 25 mg/kg methotrexate given to rats fed an elemental diet. Rats fed a regular chow diet show no clinical evidence of gastrointestinal morbidity or mortality at this dose. The etiology of this enhanced toxicity is not clear, however. It this study rats were randomized to receive an elemental diet (n = 45) or a regular chow diet (n = 45) for 7 days. They were then given a bolus dose of 3H methotrexate (25 mg/kg) intraperitoneally. At 20 and 40 minutes and at 1, 2, 12, 24, 48, 72, and 96 hours after injection, five animals from each group were anesthetized, and mean methotrexate levels in bile and serum, and tissue methotrexate concentrations in proximal, mid, and distal small intestine and in liver were obtained. Mean methotrexate levels in bile were significantly elevated in rats fed an elemental, chemically defined diet at 12, 24, 48, and 72 hours compared with regular diet fed rats. Mean serum methotrexate levels were elevated in both the inferior vena cava (IVC) and portal vein (PV) at 12 (IVC), 24 (PV), and 48 hours (IVC) in elemental, liquid diet fed rats. There were no statistical differences between methotrexate levels in rats fed an elemental diet or a regular chow diet in proximal or mid small intestine at any of the time points measured. In the distal small intestine, methotrexate levels were significantly elevated at 24 hours in rats fed an elemental, chemically defined liquid diet (P less than 0.03) compared with regular diet fed rats. Methotrexate levels in liver of rats fed an elemental, chemically defined liquid diet were significantly elevated at 24 and 48 (P less than 0.05) hours. Administration of an elemental, chemically defined liquid diet prolongs the enterohepatic circulation of methotrexate in rats and delays clearance of the drug from the systemic circulation. Thus, prolonged exposure of methotrexate to the cells of the intestinal mucosa explains the increased gastrointestinal side effects of the drug in rats fed an elemental, chemically defined liquid diet. If these results are applicable to man, elemental, chemically defined liquid diets are contraindicated as the sole nutritional source in patients receiving methotrexate. Such qualitative alteration of dietary intake may be a factor in the unpredictability of gastrointestinal side effects associated with high dose methotrexate administration.

Animals↗
PubMed1987

Regional infusion for colorectal hepatic metastases. A randomized trial comparing the hepatic artery with the portal vein.

To evaluate which site of infusion maximizes tumor response to regional hepatic chemotherapy, 25 patients were randomized preoperatively to receive chemotherapy administration via hepatic artery or portal vein catheters. Of the 25 patients, five did not have catheters placed due to extrahepatic disease, and one patient did not receive infusion chemotherapy. Continuous floxuridine infusion was given at a dosage of 0.3 mg/kg/d, alternating with saline solution every two weeks. The mean percentage of hepatic tumor replacement (36% vs 41%), mean serum alkaline phosphatase level (218 vs 179 IU/mL), and mean plasma carcinoembryonic antigen level (689 vs 563 ng/mL) were similar in both groups. Four (50%) of eight hepatic artery patients responded to treatment compared with 0/11 portal vein patients. Ten of 11 portal vein patients showed progressive tumor growth; nine of these patients were crossed over to arterial infusion. Three (33%) of these nine patients had an objective tumor response with the hepatic arterial infusion. This prospective, randomized clinical trial demonstrates significantly improved tumor response after hepatic arterial infusion compared with portal vein infusion.

Adenocarcinoma↗
PubMed1987

Subungual melanoma: a 25-year review of cases.

The purpose of this study was to evaluate subungual melanoma as a site-specific entity, to determine the influence of regional nodal involvement, and to ascertain where possible the role of histologic grading of the primary site. Thirty-three patients with subungual melanoma whose median age was 56 yr underwent treatment between 1950 and 1975. There were 11 male and 22 female patients. Forty-eight per cent of lesions were 11 male and 22 female patients. Forty-eight per cent of lesions occurred on the hand. Of 23 clinical stage I patients, seven patients underwent amputation only, while 16 patients underwent amputation and regional nodal dissection. Histologic examination of the primary tumor suggested a trend towards thicker/ulcerated lesions to be associated with metastatic melanoma in regional lymph nodes and/or death due to disease. Early survival patterns favored female patients but there was no significant difference in 10-year survival when analysed by patient sex. Clinical/pathologic stages were the most significant factors affecting long-term survival with 5- and 10-year survivals of 66% and 55% in stage I patients and 22% and 0% in stage II patients.

Adult↗
PubMed1987

Immediate postoperative jejunostomy feeding. Clinical and metabolic results in a prospective trial.

A prospective clinical trial was designed to evaluate the efficacy of postoperative jejunostomy feedings using high (44 percent) and low (15 percent) branched-chain amino acid elemental diet formulations compared with no jejunostomy feedings in a homogeneous surgical population. Twenty-eight patients undergoing radical cystectomy and ileal diversion were randomized to the high branched-chain amino acid formula (11 patients) or the low branched-chain amino acid formula (9 patients). Eight patients received a 5 percent dextrose in water solution intravenously and served as a control group. Mean caloric intake per day in each group was 1,543 calories, 1,697 calories, and 550 calories, respectively; whereas the mean nitrogen intake of each group was 6.5 +/- 2.1 g/day, 8.2 +/- 2.4 g/day, and 0 g/day, respectively. Mean weight changes were minus 0.7 percent, 0.7 percent, and minus 0.3 percent, respectively. The mean daily nitrogen balance was minus 1.6 +/- 3.5 g/day, minus 1.1 +/- 4.4 g/day, and minus 6.6 +/- 1 g/day (p less than 0.001). Five patients (25 percent) in the jejunostomy groups progressed to an oral diet more rapidly than the control group, but gastrointestinal complications occurred in 11 patients (55 percent). Immediate postoperative jejunostomy feedings resulted in improved nitrogen balance compared with the control group values, but no metabolic advantage was noted by infusing a high branched-chain amino acid formula. Improved return to normal gastrointestinal function was noted in 25 percent of jejunostomy patients, but the gastrointestinal complications noted limited the overall usefulness of this technique.

Abdomen↗
PubMed1987

Alteration of methotrexate toxicity in rats by manipulation of dietary components.

Administration of a chemically defined, elemental diet to rats given 20 mg/kg of methotrexate intraperitoneally has consistently resulted in a 100% mortality from severe enteritis within 156 h. This study examined the importance of specific dietary components in the etiology of this enhanced toxicity. Rats were given their respective diets for 7 days, whereupon methotrexate (20 mg/kg) was given intraperitoneally, and percent of survivors was recorded. Varying the concentration of carbohydrate as polysaccharide (0%, 50%, 100%) (n = 30) had no effect on survival. An increase in the percent of protein as polypeptide (0%, 25%, 50%, 75%, 100%) (n = 50) in the elemental diet resulted in a progressively significant increase in percent survival. Addition of either fat or bulk to this elemental diet had no effect on survivorship. Serum and bile methotrexate levels of rats fed an elemental liquid diet (whether or not all of the protein was provided as polypeptide) were significantly increased from 12 to 72 h (p less than 0.03) compared with rats fed a regular Chow diet. When the protein content of the elemental liquid diet was provided as 100% polypeptide, serum and bile methotrexate levels were significantly lower at 48 h compared with the elemental diet group given 100% of protein as amino acid. Administration of methotrexate to rats fed an elemental liquid diet in which all of the protein is provided as amino acids is extremely toxic to the gastrointestinal tract, probably as a result of delayed clearance of the drug from the systemic circulation and from bile. This toxicity is alleviated by the provision of protein as polypeptide in the elemental diet. No toxicity to the drug is seen at this dose in rats fed a regular Chow diet. If these results are applicable to humans, the use of elemental liquid diets as the only source of enteral nutrition would appear contraindicated in patients receiving methotrexate.

Amino Acids↗
PubMed1987

Modulation of doxorubicin uptake by epinephrine in the VX-2 carcinoma.

The purpose of regional chemotherapy is to deliver maximal drug concentrations to localized unresectable tumors, to minimize systemic toxicity, and to improve tumor response to treatment. Manipulation of regional blood flow by vasoactive agents could further increase tumor drug levels. This study evaluates the effect of hepatic artery infusion of epinephrine on tumor and liver doxorubicin uptake. New Zealand White rabbits (n = 17) were implanted with hepatic VX-2 carcinomas which were allowed to grow to 2-3 cm in diameter. Doxorubicin (3 mg/kg) +/- [14C]doxorubicin (2.5 microCi) was given alone (controls) or following low- (5 micrograms) or high- (15-50 micrograms) dose epinephrine infusion into the hepatic artery. Heart, liver, and tumor were obtained 30 min after infusion for determination of doxorubicin concentration. The doxorubicin liver concentrations were similar in all three groups but tumor levels decreased from 26.6 +/- 16.3 to 6.7 +/- 2.8 and 6.6 +/- 4.3 nmole/g in the epinephrine groups. Myocardial levels were reduced by the high-dose epinephrine (6.8 +/- 2.2 nmole/g) when compared to controls (11.3 +/- 2.1 nmole/g) or low-dose epinephrine (11.5 +/- 1.8 nmole/g). The liver concentration of doxorubicin was not significantly affected by intraarterial epinephrine. The myocardial doxorubicin concentration was affected only by epinephrine doses sufficient to cause severe systemic vasoconstriction. The decrease in tumor doxorubicin concentration to low-dose (5 micrograms) and high-dose (15-50 micrograms) epinephrine suggests that intraarterial epinephrine limits doxorubicin uptake by tumor.

Animals↗
PubMed1987

The binding of host-selective toxin analogs to mitochondria from normal and ;texas' male sterile cytoplasm maize.

Tritium-labeled toxin analogs were prepared by reduction with NaB(3)H(4) of either the toxin from Helminthosporium maydis race T or a toxin component from Phyllosticta maydis. These reduced analogs had high radiochemical specific activities, high biological activities, and plant specificities identical to the native toxins. A filtration assay was developed to test the binding of these labeled analogs to isolated mitochondria. Binding was not energy dependent nor was there measurable matrical uptake. The analogs were shown to be lipophilic, a characteristic which gave rise to considerable nondisplaceable binding. Under conditions limiting nondisplaceable binding, the displaceable binding was shown to be linear with respect to toxin concentration and unsaturable. No significant differences were observed in the binding characteristics between the mitochondria from normal and male-sterile (Texas) cytoplasm maize. The findings suggest that, at physiologically relevant concentrations, these toxin analogs permeate the membranes of susceptible and resistant mitochondria alike. The lack of demonstrable specific binding does not rule out the involvement of a classical receptor site but does indicate that other kinds of molecular interactions may be involved in the mechanisms for toxicity and specificity.

Journal Article↗
PubMed1987

Significance of a fall in serum CEA concentration in patients treated with cytotoxic chemotherapy for disseminated colorectal cancer.

'Tumour response', defined as clinical or radiological evidence of tumour shrinkage is frequently regarded as an objective of chemotherapy, rather than as a predictor of prolonged survival. This study has assessed whether a fall in the serum CEA concentration after chemotherapy for disseminated colorectal cancer is a predictor of prolonged survival and compared it with tumour response as a predictor of survival. There was a 37% improvement in median survival among patients whose serum CEA concentration fell after chemotherapy (70% of patients treated) compared with patients whose serum CEA did not fall. The use of greater than 25% clinical or radiological tumour shrinkage as a predictor of prolonged survival identified a smaller proportion (36%) of patients in whom there was a 52% prolongation in median survival compared with patients whose tumours shrank less than 25%, or did not shrink. Proportional hazards regression analysis suggested that tumour shrinkage was a stronger predictor of survival. A fall in serum CEA concentration, however, identified a group of patients whose tumours did not shrink, but who had a 27% improvement in median survival compared with those whose tumours did not shrink and whose serum CEA concentration did not fall. Monitoring of the serum CEA during the first two months of treatment appears to provide a sensitive and economical means of identifying those patients whose survival is likely to be prolonged by chemotherapy for colorectal cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

A randomized study of oral nutritional support versus ad lib nutritional intake during chemotherapy for advanced colorectal and non-small-cell lung cancer.

One hundred ninety-two patients with previously untreated metastatic cancer (102 non-small-cell lung cancer [NSCLC]; 90 colorectal cancer) were randomized to receive either ad lib nutritional intake (control group) or specific nutritional intervention during a 12-week study period when chemotherapy was administered. Those patients randomized to nutritional interventions were counselled to take oral nutrients with caloric intake equal to 1.7 to 1.95 times their basal energy expenditure, depending on their pretreatment nutritional status ("standard" group). An augmented group was counselled to have a caloric intake equivalent to that of the standard group but with 25% of calories provided as protein and additional supplements of zinc and magnesium. Counselling increased caloric intake in both tumor types but reduced weight loss in the short term only for lung cancer patients. Ninety-three NSCLC patients were evaluable for tumor response to vindesine and cisplatin. Overall, only 20.4% of the patients responded, and there were no significant differences in response rates, median time to progression, or overall duration of survival between the nutrition intervention groups and the control group. The tumor response rate to time-sequenced 5-fluorouracil (5-FU) and methotrexate in the 81 evaluable patients with colorectal cancer was only 14.8%, and no significant differences in tumor response rates were noted between the three groups. Furthermore, the median time to progression and overall duration of survival were not different for the control, standard, and augmented groups. Nutritional interventions using dietary counselling had no impact on the percent of planned chemotherapy dose administered, the degree of toxicity experienced by patients, or the frequency of treatment delays. A multivariate prognostic factor analysis demonstrated that for lung cancer, the percent of weight loss, serum albumin concentration, and presence of liver metastases were significant (P less than .05) and independent prognostic variables for survival duration. For colorectal cancer, serum albumin, alkaline phosphatase, lactic dehydrogenase (LDH) levels, and percent targeted caloric intake (TCI) were significant independent predictors of survival duration.

Adult↗
PubMed1987

Tumor and liver drug uptake following hepatic artery and portal vein infusion.

Anatomic dye injection studies of the blood supply of colorectal hepatic metastases suggest that tumors are supplied predominantly by the hepatic artery. Using 13N amino acids with dynamic gamma camera imaging in patients with colorectal hepatic metastases, it has been shown that hepatic artery infusion results in a significantly greater nutrient delivery to tumor compared with portal vein infusion. However, direct measurements of drug levels in tumor following hepatic artery and portal vein infusion in humans have not previously been reported. Patients with metastatic colorectal cancer confined to the liver received fluorodeoxyuridine (FUdR) through the hepatic artery or through the portal vein. All patients had previously failed systemic chemotherapy. Five patients with hepatic artery catheters were matched (by age, serum lactic dehydrogenase levels, percent hepatic replacement, and tumor size) with five patients with portal vein catheters. At operation, 3H-FUdR (1 microCi/kg) and 99mTc-macroaggregated albumin (MAA) (6 mCi) were injected into the hepatic artery or portal vein. Liver and tumor biopsies were obtained two and five minutes later. 3H and 99mTc were measured per gram tissue by scintillation and gamma counting. The mean liver levels following hepatic artery infusion (23.9 +/- 11.4 nmol/g) and portal vein infusion (18.4 +/- 14.5 nmol/g) did not differ. However, the mean tumor FUdR level following hepatic artery infusion was 12.4 +/- 12.2 nmol/g, compared with a mean tumor FUdR level following portal vein infusion of 0.8 +/- 0.7 nmol/g (P less than .01). This low level of tumor drug uptake after portal vein infusion of FUdR predicts minimal tumor response to treatment via this route. Thus, regional chemotherapy for established colorectal hepatic metastases should be administered through the hepatic artery.

Aged↗
PubMed1987

Distribution of fluorodeoxyuridine uptake in the liver and colorectal hepatic metastases of human beings after arterial infusion.

Little is known about drug distribution in tumor metastases or in the liver after hepatic arterial infusion. This information is important for planning strategies to enhance tumor drug uptake and to improve tumor response to therapy. Dye injection studies have demonstrated hepatic tumor vascular supplies in an anatomic manner, but offer no physiologic data. To evaluate hepatic drug distribution in patients with metastases to the liver and colon and rectum (6-3H) 5-fluorodeoxyuridine (FUdR) and 99m-technetium (TC) macroaggregated albumin (MAA) were infused through the hepatic artery prior to lobectomy of the right hepatic lobe in three patients and before wedge resection of a metastasis in one patient. Forty to 100 specimens of the tumor and liver taken at biopsy were assayed in order to map drug and albumin distribution. Nuclide scanning of the specimen was performed upon two patients. A linear relationship between levels of 3H (representing fluoropyrimidine metabolites) and 99mTc (representing blood flow) was demonstrated in both the tumor (correlation coefficients 0.69 to 0.87, p less than 0.01) and liver (correlation coefficients 0.76 to 0.90, p less than 0.001). The liver immediately adjacent to the tumor retained substantially more 99mTc-MAA than either the tumor itself or liver remote from the tumor, as demonstrated by both nuclide scanning and tissue biopsies. The rim of the liver adjacent to the tumor with enhanced 99mTc uptake had a different histologic appearance from a "normal" liver at a distance from the tumor in all instances. A radionuclide hepatic scan showing increased tumor uptake of 99mTc-MAA after arterial injection predicts an increased likelihood of tumor response to treatment. The results of this study demonstrate for the first time, in human beings, that increased 3H-FUdR uptake occurs in portions of the tumor which retain more 99mTc-MAA and explains the capacity of the arterial 99mTc-MAA perfusion scan to predict tumor response in the treatment of metastases to the liver and colon and rectum.

Adult↗
PubMed1987

Muscle amino acid flux in patients receiving branched-chain amino acid solutions after surgery.

The metabolism and efficacy of branched-chain amino acids (BCAAs)-enriched parenteral solutions in patients after surgery are unclear. This prospective clinical study compared two groups of patients (n = 13) receiving either a 25% BCAA solution or a 45% BCAA solution at 30 kcal/kg/day and 1.5 gm protein/kg/day for 7 days after operation. Whole-body nitrogen balance and forearm muscle amino acid and ketoacid flux were measured. There were no significant differences between the two groups in mean cumulative nitrogen balance (+13.1 gm versus +18.0 gm) between the two groups. Patients receiving the 45% BCAA solution had significant mean uptake of total BCAA, leucine, and isoleucine compared with results in patients receiving the 25% BCAA solution. Despite this increased uptake of BCAA in the 45% BCAA group, there was no increased efflux of alanine, glutamine, or the BCAA ketoacids, ketoisocaproic, ketoisovaleric, or ketomethylvaleric. However, increased release of aspartate was noted in the 45% BCAA group compared with the 25% BCAA group. Thus use of a 45% BCAA-enriched solution infused in patients after surgery results in a significant increase in forearm muscle uptake of the BCAA that is not demonstrated in whole-body nitrogen economics.

Adult↗
PubMed1986

Nutritional support in the cancer-bearing host. Effects on host and tumor.

Cancer patients have the highest prevalence of malnutrition of any group of hospitalized patients. The potential causes of this malnutrition are numerous, as elements of both starvation and stress are evident in the cancer-bearing host. The presence of the tumor alone may lead to reduced intake of nutrients and treatment modalities of surgery, chemotherapy, and radiation therapy further exacerbate nutritional deficits. It is clear that the tumor requires energy substrates to grow, and that these substrates are exacted from the host. Animal studies identify progressive nutritional depletion concomitant with increasing tumor growth during ingestion of a regular diet. This appears predominantly due to reduced dietary intake in addition to host metabolic alterations. In animal/tumor models deliberate dietary protein depletion results in severe host weight loss, but also causes diminished tumor growth rates. Dietary manipulation in these animal/tumor models have demonstrated methods of improving tumor response to chemotherapy by manipulation of tumor growth rates. In addition, drug-pharmacokinetics have been altered by dietary manipulation. However, data from animal/tumor models are not directly applicable to man since the tumor in animals usually results in the death of the host within six to eight weeks. Nevertheless, controlled laboratory studies in animals provide basic metabolic information which promotes understanding of host/tumor relationships in man. In cancer patients malnutrition has prognostic value, leads to a distortion of body composition with erosion of body protein and fat stores, and compromises the delivery of adequate therapy. There is no direct objective evidence of accelerated tumor growth in humans with cancer who receive nutritional support as part of their treatment regimen. The host benefits to the extent that body composition is at least maintained during the period of nutritional repletion. Thus, nutritional support provides support to the patient during periods of treatment and dietary deprivation. No improvement in the tumor's response to therapy, however, has been demonstrated by this approach.

Animals↗
PubMed1986

Intra-arterial infusion of doxorubicin with degradable starch microspheres. Improvement of hepatic tumor drug uptake.

Regional infusion chemotherapy delivers higher drug concentrations to the tumor than other methods and may decrease systemic drug levels. We evaluated the efficacy of degradable starch microspheres (DSMs) to further increase drug delivery to hepatic tumors. Rabbits implanted with hepatic Vx-2 tumors were treated with hepatic arterial infusion of doxorubicin hydrochloride labeled with carbon 14 with and without DSMs. Tissue levels of doxorubicin were measured in the heart, liver, and tumor 30 minutes after drug infusion. Blood drug levels, as well as biliary and renal excretion rates of doxorubicin, were determined. In rabbits receiving the drug alone, doxorubicin uptake by the tumor and liver were 17.1 +/- 12.8 and 55.3 +/- 9.5 nmol/g of wet weight tissue (mean +/- SD), respectively. In rabbits receiving doxorubicin mixed with DSMs, the tumor and hepatic drug levels were 59.7 +/- 24.9 and 50.7 +/- 4.8 nmol/g, respectively. The tumor drug level was significantly higher in the group that received DSMs compared with the group that received only the drug; the hepatic drug uptake was unchanged. Peak blood and cardiac drug levels were decreased by the coinfusion of drug and DSMs, suggesting that tumor response rates may be improved and systemic toxicity diminished by the use of DSMs in regional infusion chemotherapy.

Animals↗
PubMed1986

Impact of antitumor therapy on nutrition.

Surgery, radiation, and chemotherapy can result in further deterioration in nutritional status in patients who are frequently malnourished as a consequence of their underlying malignancy. Many of the effects are transient, and patients who have a good performance status may exhibit minimal alterations in nutritional parameters during the course of treatment. However, antitumor treatment may enhance morbidity, and in some, it leads to mortality if patients are in poor nutritional status ab initio. Such malnourished patients must be recognized prior to initiation of treatment, and steps must be taken to maintain adequate nutrition. The known toxic effects of many cancer therapeutic regimens must be weighed against their potential benefits.

Antineoplastic Agents↗