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PubMed1990

Work practices and policies of hospital pharmacists preparing antineoplastic agents.

Hospital-based female pharmacists were asked about workplace practices and conditions, use of protective equipment, and formal hospital guidelines governing exposure to antineoplastic agents. Special preparation areas dedicated to antineoplastic agents were absent in 13.4% of the workplaces. Vertical laminar flow hoods were unavailable for 27.7% of the respondents. Although protective gloves were worn by the majority (87.9%), safety glasses and facial masks were used infrequently. More than 40% of the group reported skin contact with cytotoxic drugs at least once a month. Eighty-three percent of all respondents reported that their institution had a formal policy governing the handling of antineoplastic agents. Medical surveillance for exposed employees, however, was available in only 28% of the workplaces.

Antineoplastic Agents↗
PubMed1995

DNA damage in nurses handling antineoplastic agents.

In 91 nurses from several divisions of four hospitals in Germany the genotoxic effect caused by the occupational exposure presumably due to mixing of antineoplastic agents was investigated. The amount of DNA single strand breaks and alkali labile sites in the peripheral mononuclear blood cells of the nurses was measured using the alkaline elution method. In ten nurses handling antineoplastic agents not using recommended safety precautions such as safety hoods, gloves or surgical masks a 50% higher level of DNA strand breaks and alkali-labile sites (p < 0.005; U-test) was detected compared to 54 controls. After applying recommended safety precautions a statistically significant decrease (p < 0.01) in the level of DNA strand breaks to the level of controls was observed. In other nurses handling antineoplastic agents by using adequate safety equipment no significantly different amount of DNA strand breaks compared to that of controls was detected. No significant correlation between the level of DNA strand breaks and the weekly contact frequency, the life-time exposure to antineoplastic agents, or the time elapsed since the last handling of the drugs was found in this study.

Adult↗
PubMedDate not supplied

Exposure of pharmacy technicians to antineoplastic agents: reevaluation after additional protective measures.

In the past, special guidelines and protective measures have been introduced to protect hospital workers during the handling of antineoplastic agents; nevertheless, it was found that they did not prevent the uptake of these toxic compounds. In response, additional protective measures were introduced, including adaptations of the laminar downflow hood, use of special masks, use of double pairs of gloves, and replacement of ampules with vials. In the current study, the authors compared the effects in these additional measures with results of a previous study. Cyclophosphamide, 5-fluorouracil, and methotrexate constituted 81% of the antineoplastic agents prepared; therefore, the investigators monitored these compounds again by personal air sampling and by determining the levels of contamination on masks and gloves. Cyclophosphamide in the urine of workers was also measured. During preparation, investigators concluded that there were lower concentrations of cyclophosphamide in the air than had occurred in the previous study. Replacement of ampules with vials (i.e., 5-fluorouracil) resulted in a significantly diminished contamination of latex gloves. Cyclophosphamide was detected in urine samples provided by six of nine technicians; the maximum amount excreted over 5 d was 2.6 microg. The mean cyclophosphamide excretion/d was not significantly lower than that found in the previous study (0.16 microg and 1.44 microg, respectively). Despite an intensified hygienic regimen, exposure to antineoplastic agents cannot be reduced if the reasons for exposure remain unknown.

Air Pollutants, Occupational↗
PubMed1981

Classification of antineoplastic agents by their selective toxicities toward oxygenated and hypoxic tumor cells.

The cytotoxicities of a number of antineoplastic agents to oxygenated and hypoxic EMT6 mouse mammary tumor cells in culture were examined. Based on the relative sensitivities of cells under aerobic and hypoxic conditions, drugs were placed into three categories. Drugs that were preferentially toxic to cells under oxygenated conditions were classified as type 1 agents; this group includes bleomycin, procarbazine, streptonigrin, actinomycin D, and vincristine. Type 2 agents were those preferentially toxic to cells under hypoxic conditions. These include mitomycin C and Adriamycin. On the basis of other published reports, the glucose analogs, 5-thio-D-glucose and 2-deoxy-D-glucose, and the radiosensitizers, misonidazole and metronidazole, can also be placed in this category. Several antineoplastic agents showed no major preferential toxicity to cells under the conditions of oxygenation or hypoxia used in these experiments and were placed in a third class. This group (type 3) includes 1,3-bis(2-chloroethyl)-1-nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, cis-diamminedichloroplatinum(II), 5-fluorouracil, and methotrexate. The success of many combination chemotherapy and combined modality treatments may be due to their ability to kill both the hypoxic and aerobic cell populations of solid tumors. Future chemotherapeutic regimens for the treatment of solid tumors should include agents and modalities directed toward the hypoxic cell population of the tumor, as well as toward the proliferating and nonproliferating tumor cell compartments; a therapeutic approach to the selection of antineoplastic agents for use in combination based upon physiological considerations of the architecture of solid tumors is presented.

Animals↗
PubMed1993

Inhibition of basal and TGF beta-induced fibroblast collagen synthesis by antineoplastic agents. Implications for wound healing.

Antineoplastic drugs, given in the perioperative period, are thought to be a hazard to wound repair. Since fibroblast collagen synthesis is crucial to healing, we examined the effects of bleomycin, cisplatin and 5-fluorouracil on collagen synthesis in confluent cultures of fibroblasts from human colon and skin. The drugs were added in final concentrations between 0.1 and 50 microM. Bleomycin did not affect collagen synthesis in colon fibroblasts but inhibited synthesis in skin fibroblasts. Collagen synthesis in colon fibroblasts was strongly, and specifically, inhibited by cisplatin while synthesis in skin fibroblasts was affected only slightly. 5-Fluorouracil had no effect whatsoever on the collagen synthetic capacity in either colon or skin fibroblasts. If skin fibroblasts were cultured in the presence of transforming growth factor beta (TGF beta), the antineoplastic agents inhibited the TGF beta-stimulated collagen synthesis at far lower concentrations than those needed to suppress non-stimulated synthesis. This effect was not observed in fibroblasts from colon. The possible implications of these observations, as pertain to the use of perioperative chemotherapy, are discussed. Since 5-fluorouracil did not directly affect collagen synthesis in colon fibroblasts under any of the conditions tested it is suggested that the data support the contention that this drug is relatively harmless for intestinal healing.

Bleomycin↗
PubMed1975

The bioavailability in man of ICRF-159 a new oral antineoplastic agent.

The bioavailability of the antineoplastic agent, ICRF-159, has been examined in 12 patients receiving the drug in single and subdivided dose schedules in an attempt to account for the differences in toxicity found with the different schedules clinically. Recovery of radioactivity in the urine after single large doses (13.3-19.4 g) was 8.5 +/- 3.0% of the administered dose. After doses of 3.8-5.55 g recovery was 22.7 +/- 10.5% and after the same dose subdivided into 3 equal aliquots it was 52 +/- 8.7%. Unrecovered radioactivity was largely accounted for in the faeces. Plasma radioactivity levels in 2 patients after high and low dose were equivalent. Toxicity of the drug paralleled urinary recovery of radioactivity. It is concluded that schedule dependence of toxicity of ICRF-159 is at least partly due to bioavailability factors.

Administration, Oral↗
PubMed2000

Determination of the vaporization of solutions of mutagenic antineoplastic agents at 23 and 37 degrees C using a desiccator technique.

This study evaluated the ability of mutagenic antineoplastic agents to vaporize at room temperature (23 degrees C) and 37 degrees C. A bacterial mutagenicity assay was used to determine the mutagenicity of these agents in the vapor phase. Open plates of bacteria were exposed to varying amounts of drug solutions in sealed glass containers for 24h. The drug solutions were prepared as they would be for patient treatment and were tested at 0.25, 0.5 and 1.0 ml of each drug solution per 10 l of air. Following exposure, the plates exposed at 23 degrees C were incubated an additional 48 h at 37 degrees C to allow for expression of mutations. Those exposed at 37 degrees C were incubated for an additional 24h at 37 degrees C. Carmustine, cyclophosphamide, ifosfamide, thiotepa, and mustargen demonstrated vaporization at 37 degrees C. Carmustine and mustargen also demonstrated significant vaporization at 23 degrees C, while cyclophosphamide demonstrated a 50% increase in revertants at this temperature. In addition, sodium azide, a known mutagen used as a control was also mutagenic as a vapor at both temperatures. Doxorubicin, cisplatin, etoposide, 5-fluorouracil and mitomycin were not detected as vaporizing in this assay. The study found that vaporization of standard solutions of some antineoplastic agents is possible at room temperature and increases as the temperature increases. Therefore, vaporization of spilled antineoplastic agents may present an additional route of exposure to healthcare workers through inhalation.

Antineoplastic Agents↗
PubMed1999

Surface contamination with antineoplastic agents in six cancer treatment centers in Canada and the United States.

The level of contamination by antineoplastic agents in drug preparation and administration areas in cancer treatment centers in Canada and the United States was determined. Sampling locations at three cancer treatment centers in Canada and three centers in the United States were selected (biological safety cabinets, countertops, and floors in and adjacent to preparation areas; tabletops, chairs, and floors in administration areas). A solution of sodium hydroxide (0.03 M) was spread over the surface of each area. The surface was wiped with one or two absorbent tissues, which were then stored in plastic screw-top containers. Samples were stored at -40 degrees C before analysis of ifosfamide content (U.S. centers only) and cyclophosphamide content by gas chromatography in tandem with mass spectroscopy-mass spectroscopy and fluorouracil content by reverse-phase high-performance liquid chromatography with ultraviolet-light detection. Measurable amounts of the antineoplastic agents were detected in 75% of the pharmacy samples and 65% of the administration samples. In general, the levels of contamination were higher in the pharmacy areas than in the drug administration areas. The pharmacy area at the site with the highest number of drug preparations had considerably more drug contamination than the other sites. The results were similar for Canadian and U.S. centers. Substantial levels of contamination from three antineoplastic agents were detected on a variety of surfaces in pharmacy drug preparation areas and drug administration areas in six cancer treatment centers in Canada and the United States.

Antineoplastic Agents↗
PubMed2000

Long-term outcomes of children exposed to antineoplastic agents in utero.

The long-term outcomes of children exposed to antineoplastic agents in utero are not well-defined. Existing data are significantly limited by small numbers, heterogeneous patient populations and regimens, brief and unsystematic assessments in follow-up, and substantial publication bias. Larger, prospective analyses are necessary to draw definitive conclusions. Potential long-term effects include transplacental carcinogenesis, gonadal dysfunction and infertility, compromised physical and neurologic growth and development, transplacental mutagenesis of germ-line tissue, and teratogenicity and carcinogenesis in subsequent generations. Ideally, chemotherapy should be delayed until the fetus is as fully developed as possible. If maternal outcome would be significantly compromised with deferral until delivery, choice and timing of agents should be based on current knowledge of the most effective, least teratogenic drugs. Knowledge of agent-specific toxicities and their potential for late manifestation in the progeny may be prudent in the vigilant long-term follow-up of children exposed to antineoplastic agents in utero.

Antineoplastic Agents↗
PubMed1986

[Flow cytometric studies of brain tumors--5: New sensitivity test of antineoplastic agents for brain tumors and its clinical application].

Flow cytometry (FCM) has been used not only for the judgement of malignant tumor cells but also for the evaluation of chemotherapy. Recently, we established a new application of FCM for the choice of the best antineoplastic agent in the chemotherapy of brain tumor. At first, the system of sensitivity test was developed through the preliminary study using established brain tumor cell line. Antineoplastic agents were contacted with the cells in the monolayered culture and the cell viability and the changes of DNA-histogram were analyzed by FCM. The cell viability was measured with the staining of fluorescein diacetate, and DNA-histogram was analyzed by the staining of propidium iodide. The best agent was judged based on the changes of the cell viability and cell cycle. The cytocidal and cytostatic effects were evaluated quantitatively, showing coincidence with the sensitivity of the cells to the appropriate antineoplastic agent. Secondary, this system was applied for the 15 malignant tumor cases. In these cases, the best antineoplastic agent could be selected through this method. Present system will be applied for the clinical cases continuously. Sensitivity test by FCM could be established in vitro system, and will be of much value clinically.

Animals↗
PubMedDate not supplied

Comparative chemical and biological studies of four prototype phosphoraziridine antineoplastic agents.

The chemical alkylating activities of four prototype phosphoraziridine antineoplastic agents were compared with their biological effects on V-79 Chinese hamster lung fibroblasts. It was found that the chemical reactivity patterns correlate well with all of the biological parameters examined in this study, i.e. cytotoxicity, DNA synthesis, and production of alkali labile strand breaks. Specifically, the 2,2-dimethylaziridine derivatives (AB-132 and AB-163) showed higher initial activities reaching a plateau after a short reaction time in all of the systems used in this study while the unsubstituted aziridine derivatives (AB-100 and D-63) reacted more slowly but continued to exert their action in a linear fashion to produce greater overall effects. These findings are consistent with the conclusion that the difference between the time-dependent biological activities of these drugs closely follows the different chemical mechanisms of their alkylating reactions (SN1 vs SN2). The more rapid action and subsequent hydrolytic inactivation of the 2,2-dimethylphosphoraziridines as effective alkylators could be the basis of their lower hemopoietic toxicity compared to conventional alkylating agents including their own C-unsubstituted aziridine analogs. The much more rapid action of the 2,2-dimethylphosphoraziridines on DNA inside the cell may have some bearing on their radiation potentiating activity, but this aspect and the cholinesterase inhibitory activity of these agents (which may depend on phosphorylation) were not investigated in the present study.

Alkylating Agents↗