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At least 19 recordsLinked to original sources

Effect of tolmetin sodium dihydrate on adhesion formation by intraperitoneal administration of antineoplastic agents.

Antineoplastic agents are currently being administered through catheters placed intraperitoneally to treat cancer localized to the peritoneum. This route allows for high local concentrations of antineoplastic drug at the tumor site with low levels of the drug systemically, thereby reducing the systemic toxicity. However, there are complications with this mode of delivery, including a decrease in catheter patency and induction of adhesion formation, which leads to decreased drug dispersion and limits continuing drug administration. A model was developed in rats to mimic this method of antineoplastic drug administration that produced fibrin deposition around the catheter and adhesion formation involving bowel, intestines and liver. All antineoplastic agents tested, including Adriamycin, methotrexate, bleomycin, mitoxantrone and cisplatin, induced moderate to severe adhesion formation with varying effects on catheter patency. When an intraperitoneal bolus of tometin encapsulated in liposomes was tested with Adriamycin delivered via an osmotic minipump, a reduction in adhesion formation was observed. However, highly significant adhesion reduction was found when tolmetin was coadministered with the antitumor agents.

Animals↗

Interactions of antimicrobial agents and antineoplastic agents.

The in-vitro interactions of four antimicrobial agents (piperacillin, dibekacin, minocycline, norfloxacin) and four antineoplastic agents (mitomycin C, bleomycin, doxorubicin, 5-fluorouracil) were examined by the chequerboard dilution method using 108 clinical isolates of four species of Gram-negative bacilli. Among the antimicrobial agents, piperacillin showed the greatest degree of synergism and norfloxacin the least. The frequency of synergism was essentially similar among the antineoplastic agents, although 5-fluorouracil was more frequently synergistic than other antineoplastic agents against Pseudomonas aeruginosa. Among the four species, synergism was most frequently shown against Proteus vulgaris and least against Escherichia coli. Antagonism was rarely seen.

Anti-Bacterial Agents↗

Acute occupational exposure to antineoplastic agents.

Antineoplastic agents may exhibit effects not only in patients therapeutically exposed, but also in health workers who prepare and administer these drugs. Concern to date has focused on long-term health consequences, including adverse reproductive outcomes, altered immunity, and increased cancer risk. The burgeoning use of these drugs for non-malignant illnesses has enlarged the health worker population at risk beyond oncology personnel to include professionals in immunology, rheumatology, nephrology, and dermatology. We report here two cases of hospital workers who experienced acute adverse health effects resulting from occupational exposure to antineoplastic drugs. We believe such acute events are under-reported, and that they demonstrate the need for physician awareness regarding their management.

Adult↗

Antineoplastic agents. 487. Synthesis and biological evaluation of the antineoplastic agent 3,4-methylenedioxy-5,4'-dimethoxy-3'-amino-Z-stilbene and derived amino acid amides.

An efficient synthesis of 3,4-methylenedioxy-5,4'-dimethoxy-3'-amino-Z-stilbene (1c) and hydrochloride (1d) is reported. The nitrostilbene intermediate 6a was obtained via a Wittig reaction using phosphonium salt 4 and 3-nitro-4-methoxybenzaldehyde 5. A one-step reduction using zinc in acetic acid produced the synthetic objective amine 1c. The coupling of this amine with various Fmoc amino acids, followed by cleavage of the alpha-amine protecting group, resulted in a series of new cancer cell growth inhibitory amides. Amine 1c, hydrochloride 1d, glycine amide 3b, and tyrosine amide 3f had the highest level (GI50 = 10(-2)-10(-3) micro g/mL) of activity against a panel of six human and one animal (P388) cancer cell lines. Amine 1c and its hydrochloride 1d potently inhibited tubulin polymerization by binding at the colchicine site, while the amides had little activity against purified tubulin. Nevertheless, most of the amides caused a marked increase in the mitotic index of treated cells, indicating that tubulin was their intracellular target.

Amides↗

Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity--an update.

Development of effective antiemetic therapy depends upon an understanding of both the antiemetic agents and the emetogenic challenges these agents are designed to address. New potential antiemetic agents should be studied in an orderly manner, proceeding from phase I to phase II open-label trials and then to randomized double-blind phase III trials comparing new agents and regimens to best standard therapy. Use of placebos in place of antiemetic therapy against highly or moderately emetogenic chemotherapy is unacceptable. Nausea and vomiting should be evaluated separately and for both the acute and delayed periods. Defining the emetogenicity of new antineoplastic agents is a challenge, since such data are often not reliably recorded during early drug development. A four-level classification system is proposed for emetogenicity of intravenous antineoplastic agents. A separate four-level classification system for emetogenicity of oral antineoplastic agents, which are often given over an extended period of time, is also proposed.

Antiemetics↗

Antibacterial activities of antineoplastic agents.

Fourteen antineoplastic agents were examined for in vitro antibacterial activity against 101 aerobic and anaerobic bacterial isolates representing indigenous human microflora and selected opportunistic pathogens. Only 5-fluorouracil, mitomycin, and etoposide demonstrated inhibitory effects at achievable plasma concentrations, while the remaining drugs lacked appreciable antibacterial activities.

Antineoplastic Agents↗