Administration Of Antineoplastic Agents Research Articles

A closer look at chemotherapy-induced flagellate dermatitis.

BackgroundFlagellate dermatitis (FD) is a rare skin rash, which may occur following the administration of antineoplastic agents. It has been reported following the administration of bleomycin, docetaxel, trastuzumab, cisplatin, bendamustine and doxorubicin. We provide a summary of the epidemiology, aetiology, pathophysiology, and distribution of chemotherapy‐induced FD.MethodsPubMed was searched using ((flagellat*) AND (Dermat*)) OR ((Flagellat*) AND (Erythema)). The search yielded 206 publications, out of which 54 individual case reports were identified which fulfilled our inclusion criteria. Statistical analysis was performed where appropriate.ResultsFemale patients were slightly more likely to develop FD compared to males. In the majority of cases FD appeared on the upper and lower limbs and pruritus was an accompanying feature in 51% of cases. Most cases developed after the first cycle of chemotherapy and females were statistically more likely to present within the first 72 hr (p <0.05). Skin biopsies were taken in 41% of cases and this was not statistically associated with the patient’s gender, (p = 0.651), presentation within 72 hr (p = 0.076) or cancer diagnosis. Chemotherapy was stopped in 62% of patients and was associated with female gender (p = 0.0098). Most patients who received treatment were managed with topical steroids. Time for rash resolution ranged from a few weeks to four months following the discontinuation of the causative drug.ConclusionFD is a rare adverse skin effect of chemotherapeutic treatment, most commonly presenting on the upper and lower limbs of patients following their first cycle of chemotherapy. Early presentation is more common in females leading to increased likelihood of stopping chemotherapy. Biopsy findings poorly correlate with disease severity. Continuation of chemotherapy treatment in combination with topical steroids may not adversely affect rash resolution.

EFFECTIVENESS OF HEALTH EDUCATIONAL PROGRAM ON PEDIATRIC NURSES’ KNOWLEDGE REGARDING CHEMOTHERAPY ADMINISTRATION IN HIWA CANCER HOSPITAL IN SULAIMANI CITY

Background &#x0D; Cancer is the uncontrolled growth and spread of cells. Chemotherapy is a potentially life-saving medication for people with malignancies that act by targeting cancer and non-cancer rapid dividing cells. Nurses are the prominent persons exposed to these drugs during the preparation and administration of antineoplastic agents.&#x0D; Objectives &#x0D; To find out the effectiveness of educational program on pediatric nurses’ knowledge about chemotherapy administration.&#x0D; Methods&#x0D; Quasi-experimental research design (pre-posttest) has been utilized in this study. Tool of data collection was built; the program was constructed. To obtain validity (15), experts were selected from different specialties. The pilot study was done on six nurses in the pediatric department in Hiwa cancer hospital within the first two weeks of January 2018, and reliability of the tool was done. Sixty-nine nurses were selected purposively. &#x0D; Data were collected in three phases; before the educational program, the data was collected as a pre-test, an educational program which was consist of 12 sessions was applied, and the last phase collected data in the same questionnaire after the educational program as post-test. Data was analyzed by using the Statistical Package of Social sciences (V-21).&#x0D; Results&#x0D; The result of the study has shown significant differences in mean scores between pre- and post-program application, which indicates the effectiveness of the applied program to the nurses at a P-value (&lt;0.001). &#x0D; Conclusion&#x0D; According to the study’s findings, the educational program was effective, and nurses’ level of knowledge has risen after they participated in educational sessions.

Acute Myeloid Leukemia and Cirrhosis: Trends in Utilization of Induction Chemotherapy, Rate of Hospitalizations and Mortality

Introduction: The presence of underlying cirrhosis poses a serious challenge in treatment of newly diagnosed acute myeloid leukemia (AML) patients. In current practice, patients with significant hyperbilirubinemia are precluded from optimal induction and consolidation therapy. Allogenic stem cell transplant is also not a viable option for these patients. This is the first study aimed at evaluating the safety and trends of utilization of chemotherapy in subset of patients with newly diagnosed AML and comorbid cirrhosis, using the Nationwide Inpatient Sample. Methods: We designed a retrospective study using the Nationwide Inpatient Sample (NIS) data, the largest US inpatient database which includes approximately 76 million patients from 2005 to 2014. The authors identified hospitalizations for induction chemotherapy using the primary discharge diagnosis of 'encounter for chemotherapy' (ICD-9 codes -V58.1, V58.11 and V58.12) or procedure codes for 'administration of antineoplastic agent' (0010, 0015, 9925, 9928) and a secondary diagnosis of acute myeloid leukemia, myeloid sarcoma or acute monocytic leukemia. We excluded patients with relapsed disease or in remission. Amongst this population, patients with a diagnosis of cirrhosis including alcoholic, non-alcoholic and biliary cirrhosis were examined to find the differences in baseline characteristics, annual trends in the number of hospitalizations for chemotherapy and total hospitalization charges. We used logistic regression to calculate the adjusted odds ratios (aOR) for in-hospital mortality among these patients. Results: Between 2005 and 2014, a total of 514,032 admissions were identified with a primary diagnosis of chemotherapy for AML. A total of 1,310 (0.25%) admissions had an underlying diagnosis of cirrhosis. The number of hospitalizations for induction chemotherapy in patients with cirrhosis and AML had a statistically significant increase from 62 in 2005 to 195 in 2014. Interestingly, hospitalization for AML patients without cirrhosis has remained largely constant with 52,673 AML patients admitted in 2005 and 55,925 in 2014 (5.8% increase). In-hospital mortality in patients with cirrhosis and undergoing induction chemotherapy for AML was 14.5% (n=9) in 2005, decreasing to almost half at 7.1% in 2014 (n=14). In-patient mortality for AML patients without cirrhosis undergoing chemotherapy has also decreased, from 4.18% (n=2,205) in 2005 to 3.91% (n=2,190) in 2014. Patients with AML and cirrhosis were less likely to undergo treatment at academic centers (81.8%) than those without cirrhosis (87.1%, p=0.046), and they were less likely to possess private insurance (39.3% vs 33.3%, p=0.000). Mortality rate was higher in patients with AML and cirrhosis (12.2%, n=161) than in those without cirrhosis (4.5%, n=23369). The adjusted odds ratio for mortality in patients with cirrhosis was 2.01 (p=0.001), with older age (p=0.00) and caucasian race (p=0.01) being significant confounders. Average hospital cost for each admission for patients with AML and cirrhosis was ($223,723.6±$16,169), significantly higher than for those without cirrhosis ($129,383). Conclusions: Our study highlights the fact that the management of patients with AML and cirrhosis continues to be a dilemma. With the advances in chemotherapy over the last decade, there has been a positive trend with an increase in the number of hospitalizations for induction chemotherapy in patients with AML and cirrhosis as well as a decrease in mortality. However, the pace of improvement remains slow. Moreover, since cirrhosis is more prevalent in the lower socioeconomic strata, these patients are less likely to have private insurance or receive treatment at an academic center, which may contribute to suboptimal care. The increase in mortality in patients with AML and cirrhosis compared to those without cirrhosis can be explained by a compounding effect of AML on pre-existing complications of cirrhosis, such as coagulopathy, thrombocytopenia, encephalopathy, malnutrition and perturbed drug metabolism. Besides, hepatic dysfunction and hyperbilirubinemia often require chemotherapy dose reduction with preclusion of curative options. Further research is needed to develop standard guidelines and non hepatotoxic chemotherapeutic agents. Disclosures Rajeeve: ASH-HONORS Grant: Research Funding.

Risk management of in-hospital administration of anticancer drugs: impact of Raccomandazione 14 from the Italian Ministry of Health.

The different stages of antineoplastic agent management build up a complex process, from supply to prescription, preparation, and administration. All steps in this process must be carefully monitored in order to control/reduce the risk of errors that can impact on patient safety. This work overviews the prevention of medication errors in oncology, including regulatory and legislative frameworks with specific reference to the Raccomandazione 14 (Recommendation 14) issued by the Italian Ministry of Health. We searched the literature for types, causes, and contributing factors of medication errors during administration of antineoplastic agents. International guidelines and recommendations were examined, with specific focus on the Raccomandazione 14. Medication errors may occur along the entire therapeutic process, involving physicians, pharmacists, nurses, and other healthcare providers. A computerized prescribing system combined with a clinical decision support system helps physicians in minimizing prescribing errors. Hospital pharmacists play a crucial role in preventing inpatient prescription errors and in managing storage, dispensing, and compounding of the anticancer drugs. The Italian Ministry of Health issued the Raccomandazione 14 to provide the Italian health system with shared univocal procedures for anticancer drug supply, compounding, storage, prescription, and administration. Other themes addressed are patient and family involvement, humanization of cancer care, and training and accountability of the personnel involved. The most effective means of managing the risk of medication errors remains prevention, which lies on the systematic documentation of medication errors reporting systems. All professionals of the healthcare team involved in anticancer drug management and the institutional authorities are called upon to strive for any possible effort to prevent and eliminate medication errors.

Minimizing Staff Exposure to Antineoplastic Agents During Intravesical Therapy.

Exposure to chemotherapy is a daily risk for nurses in oncology infusion centers. Although significant advances have been made in developing systems to make IV administration of antineoplastic agents safer, less attention has been given to developing systems to minimize exposure risk during instillation of intravesical chemotherapy. This article describes the use of a closed system developed at a comprehensive cancer center and compares it to two closed systems reported in the literature. At a Glance • Safe handling of biohazard medications is important for all healthcare workers involved in the administration of antineoplastic agents. • Nurses need to advocate for use of chemotherapy administration systems that minimize exposure to staff and patients. • Infrequently performed procedures need to be supported by clearly specified procedural steps that are readily accessible to the nurse.

A transient myelodysplastic/myeloproliferative neoplasm in a patient with cardio‐facio‐cutaneous syndrome and a germline BRAF mutation

A male infant, born at 32 weeks gestation by cesarean because of hydrops fetalis, presented with multiple anomalies, such as sparse and curly scalp hair, absent eyebrows, frontal bossing, an atrial septal defect, pulmonary artery stenosis, and whole myocardial thickening. He was clinically diagnosed with cardio-facio-cutaneous (CFC) syndrome, and was confirmed to have a germline V-raf murine sarcoma viral oncogene homologue B1 (BRAF) c.721 A>C mutation. At 1 month of age, he presented with a transient myelodysplastic/myeloproliferative neoplasm (MDS/MPN), which improved within a month without the administration of antineoplastic agents. This is the first report of CFC syndrome with MDS/MPN. The coexistence of MDS/MPN may be related to this BRAF c.721 A>C mutation.

Chemotherapy-Knowledge and Handling Practice of Nurses Working in a Medical University of Nepal

Background: Many antineoplastic agents are known to be teratogenic and mutagenic to humans. Nurses are the main groups that are exposed to these drugs in hospital setting. Generally, the occupational activities that pose to greatest risk of exposure are the preparation and administration of antineoplastic agents, cleaning of chemotherapy spills, and handling of patient excreta. Objective: The objectives of this study were to evaluate the knowledge of nurse regarding the way of exposure of Cytotoxic Drugs (CDs) and to determine the current patterns of use of personal protective equipments while handling antineoplastic chemotherapeutic agents. Methods: An analytic cross sectional study was carried out at BPKIHS Dharan. The study was carried out on 125 nurses. The random sampling technique was used to select the study subjects using structured and semi-structured questionnaire. Collected data were analyzed using descriptive and inferential statistics. Result: More than 92% of participants reported usually wearing gloves during chemotherapy handling; 6% reported using laboratory coats as protective garments. Usual use of face and respiratory protection was less than 5%. Chemotherapy was reported to be prepared in nursing station where there are no laminar airflow hoods in 100% of work settings. None of the subjects have reportedly provided any type of medical monitoring. Conclusion: Use and availability of gloves have increased but personal protective equipment like protective garments, face and respiratory protective, when handling chemotherapy have decreased and medical monitoring of exposed employees still is neither widely practiced nor consistent with Occupational Safety and Health Administration (OSHA) guidelines.

Hypermethylated genes as biomarkers of breast cancer

Hypermethylated genes are emerging as some of the most promising, practical and powerful biomarkers for breast cancer detection and perhaps even of risk assessment. We have assembled a panel of methylated gene detection markers and tested them by Quantitative Multiplex Methylation-Specific PCR (QM-MSP) in breast cancer. Here we two pilot studies: 1) detection of cancer in DNA from spontaneous nipple discharge (SND) and 2) assessing risk, and its possible reduction in contralateral breast tissue of women undergoing treatment with aromatase inhibitors. SND is most frequently caused by intraductal papilloma (66%), but in a minority of women (~10%) it is caused by ductal carcinoma in situ (DCIS). Therefore essentially all women with SND are screened for breast cancer. All the current methods used for screening exhibit low sensitivity and specificity for detection of cancer. Mammary endoscopy (ductoscopy) appears to improve localization of lesions in patients with SND and allows retrieval of intraductal cells for diagnostic purposes. Development of a non-surgical method to reliably diagnose cancer would offer the possibility of diagnosis without surgery for the majority of women with SND who have a very low likelihood of significant neoplasia. Further, a reliable diagnostic test of intraductal pathology will enable in-situ ablation of benign lesions with either endoscopic techniques or the intraductal administration of anti-neoplastic agent. In a pilot study we investigated whether quantitative assessment of gene promoter hypermethylation could enhance detection of breast cancer in women with spontaneous nipple discharge (SND) when used in conjunction with ductoscopy. Ducts with significant visualized lesions were surgically resected (36 ducts in 33 women) and those with minimal findings were not (28 ducts in 16 women). QM-MSP data of DNA from cells in ductoscopic washings were compared to ductoscopy findings, cytology, and tissue histology. Cells from ducts with significant ductoscopic findings had higher levels of methylation while cells found in ducts with minimal findings had minimal methylation; methylation was higher in cells from ducts with malignant lesions compared to low methylation in ducts bearing benign lesions such as papilloma. RASSF1A, TWIST1, and HIN1 cumulative gene methylation accurately distinguished cells washed from ducts with cancerous vs. benign lesions (100% sensitivity, 72% specificity and AUC of 0.91 according to ROC analyses). Using QM-MSP the positive predictive value of ductoscopy more than doubled because QM-MSP has three-fold higher sensitivity than cytology in evaluation of ductal cells. This study demonstrates the potential benefit of targeting surgical ductal excision to ducts that have both high methylation and significant abnormalities on ductoscopy. Future large-scale studies to validate this approach are needed. Women with a history of breast cancer are at increased risk to develop a contralateral breast (CLB) cancer. Since gene methylation occurs early in tumorigenesis, and is frequently higher in normal tissues adjacent to a breast tumor, we hypothesized that women with a prior breast cancer would harbor higher levels of methylated genes in the CLB and that treatment with anastrozole, an aromatase inhibitor that reduces the risk of CLB cancer, would decrease methylation levels. We conducted a prospective, single-arm study in 54 postmenopausal women with hormone receptor-positive stage 0–III breast cancer who had completed local therapy, had an intact CLB, and would receive anastrozole as their sole adjuvant therapy. Of those, 33 women underwent an optional CLB biopsy both at baseline and 6 months after initiating Anastrozole. At baseline, 84% of paired samples had measurable cumulative methylation of the 6 gene panel; TWIST1, RASSF1A, and RARβ were most frequently methylated. After 6 months of anastrozole, we observed significant decreases in methylation for TWIST1, RASSF1A, and RARβ, among patients with methylation identified at baseline. These preliminary findings emphasize the need for prospective evaluation of the relationship between changes in methylation and incidence of breast cancer in high-risk women.

Evolution of intravesical immunotherapy for bladder cancer: mycobacterial cell wall preparation as a promising agent

Background: The intra-cavitary administration of antineoplastic agents for the treatment of non-invasive bladder cancer has met with variable results. Mytomicin-C is effective in the prevention of tumor recurrence when administered in the immediate post-resection period, but also exhibits activity against papillary tumors. It lacks efficacy in carcinoma in-situ (CIS) of the bladder. Bacillus Calmette-Guérin (BCG) has been shown to be effective against papillary tumors, but particularly in the treatment of CIS. Unfortunately, live BCG has serious safety limitations. Objective: To review the current situation with the use of non-viable preparations of mycobacteria (M. phlei) that have been investigated for the treatment of superficial bladder cancer in limited open-label clinical trials. Conclusion: MCC (Urocidin) has shown activity against a variety of tumor cells, both in vitro and in animal cancer models. Limited clinical trials have also shown it to be active against non-muscle invasive bladder tumors in patients who have previously failed one or more courses of chemotherapy and/or immunotherapy with BCG. An unique dual immunomodulatory and apoptotic mechanism of action has been proposed for MCC.

Cryotherapy in the prevention of oral mucositis in patients receiving low-dose methotrexate following myeloablative allogeneic stem cell transplantation: a prospective randomized study of the Gruppo Italiano Trapianto di Midollo Osseo nurses group

Severe oral mucositis is a major cause of morbidity following allogeneic hematopoietic stem cell transplantation (AHSCT). Cryotherapy, that is, the application of ice chips on the mucosa of the oral cavity during the administration of antineoplastic agents, may reduce the incidence and severity of chemotherapy-related oral mucositis. In this multicenter randomized study, we addressed whether cryotherapy during MTX administration is effective in the prevention of severe oral mucositis in patients undergoing myeloablative AHSCT. One hundred and thirty patients undergoing myeloablative AHSCT and MTX-containing GVHD prophylaxis were enrolled and randomized to receive or not receive cryotherapy during MTX administration. The incidence of severe (grade 3-4) oral mucositis, the primary end point of the study, was comparable in patients receiving or not cryotherapy. Moreover, no difference was observed in the incidence of oral mucositis grade 2-4 and the duration of oral mucositis grade 3-4 or 2-4, or in the kinetics of mucositis over time. In univariate and multivariate analysis, severe oral mucositis correlated with TBI in the conditioning regimen and lack of folinic acid rescue following MTX administration. Thus, cryotherapy during MTX administration does not reduce severe oral mucositis in patients undergoing myeloablative allogeneic HSCT. Future studies will assess cryotherapy before allogeneic HSCT.

The healing of colon anastomosis covered with fibrin glue after early postoperative intraperitoneal chemotherapy

After colon resection for colonic cancer, the administration of antineoplastic agents may prolong survival by killing residual cancer calls and preventing metastasis, but may also slow anastomotic healing. This study was designed to determine the effects of 5-fluorouracil (5-FU) and leucovorin (LEV), injected intraperitoneally, on the healing of colonic anastomoses with or without fibrin glue (FG) covering. Sixty rats were randomized to one of four groups. After resection of a transverse colon segment, an end-to-end sutured anastomosis was performed. Rats in the 5-FU+LEV and the 5- FU+LEV+FG groups received 5-FU+LEV intraperitoneally. The colonic anastomoses of the rats in the FG group and in the 5-FU+LEV+FG group were covered with fibrin glue. All rats were killed on postoperative day 8. Bursting pressure measurements were recorded and the anastomoses were examined macroscopically and histologically. The leakage rate of the anastomoses was significantly different among groups. Specifically, the leakage rate was significantly higher in the 5-FU+LEV group (40%) than in the FG and in the 5-FU+LEV+FG groups where there were no leakages (p=0.017). The mean adhesion formation score was significantly higher in rats of the 5-FU+LEV group, compared to the control (p=0.023), the FG (p=0.006) and the 5-FU+LEV+FG (p=0.006) groups. Bursting pressures were significantly lower in the 5-FU+LEV group than in the other groups (p<0.001). Also, bursting pressures were significantly lower in the control group compared to the FG and 5-FU+LEV+FG groups (p<0.001). Rats in the 5-FU+LEV+FG group had significantly greater neoangiogenesis and fibroblast activity than those in the 5-FU+LEV group (p=0.025). The early intraperitoneal postoperative administration of 5-fluorouracil plus leucovorin impaired colonic wound healing. However, the application of fibrin glue prevented the deleterious effect of chemotherapy.

Role of the antiangiogenetic drug paclitaxel on healing of intestinal anastomosis: an experimental study

The aim of intraperitoneal administration of antineoplastic agents is the prevention of the implantation of tumoral cells after surgical intervention or the treatment of peritoneal carcinomatosis. The efficiency of intraperitoneal administration of paclitaxel, which is also an antiangiogenetic agent, has been investigated recently. The aim of this experimental study was to evaluate, taking into consideration its antiangiogenetic properties, the effects of intraperitoneal paclitaxel on healing of end to end colonic anastomosis. 42 rats were allocated to 2 main groups (n = 21 for each group) to be evaluated on postperative day 3 (group A) and postoperative day 7 (group B). Each of the two main groups was divided into 3 subgroups (7 rats each). These subgroups were determined as control and two treatment groups administered paclitaxel in a dose of 2.5 mg/kg and 3.5 mg/kg intraperitoneally. Anastomosed segments of colon were harvested on postoperative day 3 or 7 and evaluated to determine bursting pressure of anastomoses, hydroxyproline levels and neovascularization with CD-31. In both groups, there were no significant differences between control and paclitaxel-treated groups with respect to bursting pressure. The level of hydroxyproline showed a significant decrease in all paclitaxel-treated groups compared with control groups (p = 0.001). Neovascularization was found to be decreased significantly on day 3 in the doses of paclitaxel 2.5 mg/kg (6.4 +/- 1.63) and 3.5 mg/kg (5.89 +/- 1.01) compared with control (8.02 +/- 0.88) (p = 0.029 and p = 0.005, respectively). There were no significant differences in neovascularization in either groups on postoperative day 7. We suggest that intraperitoneal administration of paclitaxel during surgical procedure decreases the hydroxyproline content and neovessel formation that are necessary for healing of intestinal anastomosis.

Use of heparin to lower the incidence of phlebitis induced by anti‐neoplastic agents used in ovarian cancer

To investigate whether heparin infusion with the administration of anti-neoplastic agents in ovarian cancer can reduce the occurrence of phlebitis as a complication of chemotherapy. The subjects were 20 patients with ovarian cancer who developed phlebitis following their first course of anti-cancer chemotherapy. In the subsequent chemotherapy course, 10 patients received heparin infusion of 5000 U, starting 3 h before the administration of anti-neoplastic agents and continuing concomitantly with the agents for 12 h. The other 10 patients (control) were treated with anti-neoplastic agents alone. Only one (10%) of 10 patients who had received heparin developed phlebitis, while eight patients (80%) in the control group did (P=0.005). In the heparin group, there were no toxic effects of heparin observed. The prothrombin time, activated partial thromboplastin time, fibrinogen, and platelet count did not differ before and after the completion of chemotherapy. Concurrent infusion of heparin and anti-neoplastic agents in ovarian cancer is a safe and effective method of preventing phlebitis induced by chemotherapy.

Venous Access: “What's It to You?”

Venous access has dramatically increased in importance over the last two decades and will be expected to remain an important component in the delivery of healthcare. The primary areas of healthcare that increasingly rely on venous access include hemodialysis, oncology for the administration of antineoplastic agents, infectious diseases for the provision of extended antibiotic courses, and multiple specialties that depend on the use of parenteral nutrient support. It is to be expected that as the sophistication of medicine progresses, reliance on methods of providing vascular access will continue to carry great importance while simultaneously serving as an Achilles’ heel to medical practice. This latter characteristic results from the rising prevalence of patients suffering from chronic conditions who require intensive or long-term parenteral services and exhibit access site “exhaustion.” Consequently, access site preservation should be a constant concern attendant to the placement of venous access devices. The importance of venous access is exemplified in the very extensive review provided by Vanek 1 in Part 1 in this issue and Part 2 in the June issue of NCP. The financial impact of this area alone amounts to well over a billion dollars annually when the collateral relationship that venous access has with other specialties and healthcare providers, including specialized nursing, radiology, surgery for the implantation, and care and long-term maintenance of these vascular access devices is considered. The current review provides a broad and detailed description of venous access including anatomical considerations and device options and their associated complications. Furthermore, the author tailors his presentation to the timeline required for venous access use (short-term versus long-term access) and to the specific therapeutic goals desired in various patient populations. Possibly, the most important aspect of his review is the emphasis that Vanek 1 places on complications associated with the various techniques used to gain vascular access. In this regard, catheter-related sepsis and venous thrombosis probably remain the most serious and challenging complications of venous access devices in clinical practice. Intravascular catheter-related infections are a major cause of morbidity and mortality in the United States. These infections result in substantially increased hospital costs, duration of hospitalization, and patient morbidity. The major risk factors, which influence development of infection, include patient-significant factors, site of catheter placement, associated connections of these devices, and pathogenicity of various microorganisms. For example, the mortality attributed to catheter-related Staphylococcus aureus bacteremia (8.2%) substantially exceeds the mortality attributed to coagulase-negative staphylococcal catheter-related bacteremia (0.7%). 2 Identification of these various factors and establishment of guidelines for the definition of catheter-related bloodstream infections has resulted in increased research efforts designed to reduce the incidence of these complications. Results of these efforts include protocols for the prevention of catheter-related infections during placement and algorithms for the management of these infections when they occur. 3 Additionally,

Poly(DL-lactide-co-glycolide) microporous microsphere-based depot formulation of a peptide-like antineoplastic agent

In the present investigation, a poly(DL-co-glycolide) (PLGA)-based, microspheric depot system for bleomycin (BLM) has been formulated, and the same has been evaluated in-vivo in C57BL/6J mice bearing transplantable melanoma B16F1 murine solid tumour. The microparticulate delivery systems were formulated employing a water-in-oil-in-water (W/O/W) emulsion-solvent evaporation technique and characterized in-vitro. The microspheres were injected subcutaneously to form a drug depot at the site of injection in mice bearing experimental tumours and the drug was continuously infused into the systemic circulation with progressive biodegradation. The drug-loaded microspheres exhibited improved pharmacodynamic efficacy, as evidenced by retarded tumour growth kinetics. Preliminary pharmacokinetic studies illustrated controlled release of the drug into the systemic circulation over the study period to exert an anti-neoplastic action. These studies demonstrated the feasibility of employing a PLGA-based microparticulate system as an effective biodegradable, injectable, depot-forming therapeutic system for long-term administration of anti-neoplastic agents.

Time dependency of hematopoietic growth factor coupled to chronotoxicity of carboplatin.

A growing body of data suggests that cancer therapy may be improved and toxicity reduced by administration of antineoplastic agents and cytokines at carefully selected times of the day. The time-dependent effects of each of the drugs have been documented, but not their mutual time dependencies. In the present studies we sought to determine the best time for granulocyte colony-stimulating factor (G-CSF) administration after carboplatin treatment. Carboplatin was injected in different groups of ICR mice at four different circadian stages for 5 consecutive days. Mice were synchronized with an alternation of 12 h of light (from 6:00 a.m. to 6:00 p.m.) and 12 h of darkness. After the last injection, peripheral WBCs of three mice from each group were counted every 4 h over a 24-h period. Bone marrow toxicity was estimated with the mean 24-h WBC count. The most severe leukopenia occurred in the group injected at 3:00 p.m. - 9 h after light onset. The second set of experiments evaluated the time-dependent effect of G-CSF when singly injected or given after carboplatin injections for 5 days only at 3:00 p.m. G-CSF was injected into various groups on days 8 and 9 at the same four different circadian stages. On the 10th day after the first injection, peripheral WBCs of three mice from each group were counted every 4 h over a 24-h period. Time-dependent effects were observed when G-CSF was injected as a single agent. When G-CSF was given at various times to the group with the most severe carboplatin-induced leukopenia, peripheral WBC count recovery was monitored at all injection times; it reached its highest level (exceeding even that of the control) when G-CSF was injected at 3:00 a.m. Dosing times of both chemotherapy and growth factor are relevant for optimization of carboplatin's hematologic tolerability.

Occupational exposure to antineoplastic agents and parameters for renal dysfunction.

To study the nephrotoxic effects of occupational exposure to antineoplastic agents, the early renal effect parameters retinol-binding protein (RBP) and albumin (ALB) were determined in the urine of 11 hospital workers involved in the preparation and administration of antineoplastic agents and in 23 hospital workers not involved in drug handling, who served as nonexposed controls. No significant difference was found between the exposed group and the nonexposed control group with respect to the early renal effect parameters RBP and ALB. Although it was demonstrated that the hospital workers were exposed to cyclophosphamide (CP) and probably other antineoplastic agents, the results of the present study show that these exposure levels did not cause nephrotoxic effects.

Environmental contamination and assessment of exposure to antineoplastic agents by determination of cyclophosphamide in urine of exposed pharmacy technicians: is skin absorption an important exposure route?

In the Netherlands, special guidelines and safety precautions were introduced about 10 y ago for preparation and administration of antineoplastic agents. However, little is known about the effectiveness of these measures. In this study, occupational exposure to antineoplastic agents of nine pharmacy technicians who were involved in drug preparation was investigated. Cyclophosphamide, 5-fluorouracil, and methotrexate accounted for 95% of the antineoplastic agents prepared; therefore, the presence of these compounds was monitored. During preparation, cyclophosphamide was detected in the air of the work environment (< 0.04-10.1 micrograms/m3). Contamination of and permeation through latex gloves were found for each of the three compounds. The uptake of cyclophosphamide was assessed by the determination of cyclophosphamide in urine. The drug was found in urine samples of six pharmacy technicians, including three persons who were not directly involved in the preparation of cyclophosphamide. The amounts excreted ranged from 0.2 to 19.4 micrograms/24 h. The results strongly suggest that inhalation is of minor importance for internal exposure, compared with other, presumably dermal, routes.

Alteration of coagulation and fibrinolysis systems after multidrug anticancer therapy for lung cancer

Recently, an increased frequency of thromboembolic events has been reported after the administration of anticancer drugs. The precise mechanism by which these vascular phenomena occur is unknown. The current work aims at evaluating the alterations of the coagulation and the fibrinolysis systems during the administration of antineoplastic agents by means of newly developed markers of haemostasis. This investigation comprised 25 lung cancer patients treated with multidrug combination chemotherapy. D-dimer, plasmin- α 2-antiplasmin complex, fibrin degradation products, fibrinogen, antithrombin III, thrombin-antithrombin III complex, prothrombin time and activated partial thromboplastin time were measured from samples taken before and on days 2, 5, 7, 14 and 21 after the administration of antineoplastic drugs. A significant reduction in plasma concentration of fibrinolytic activity markers, DD and PAP, was observed on days 5 and 7, and on days 2, 5, 7 and 14, respectively, following the administration of chemotherapeutic drugs. Statistically significant shortening of PT and APTT on days 2, 5, 7 and 14, as well as significant elevation of the thrombin generation marker TAT were observed on days 5 and 7 after chemotherapy. These results show that relatively higher levels of coagulation activation and a lower fibrinolytic activity occur during cytotoxic drug therapy compared with basal values. Small variations of haemostatic values and a short follow-up period may explain why no thrombotic events were observed during this study. Although further studies must be done to clarify these findings, the results of this investigation suggest that an imbalance of the coagulation-fibrinolysis system might be a contributing factor in the pathogenesis of thrombotic complications during chemotherapy.

Determination of cyclophosphamide in urine by gas chromatography—mass spectrometry

A sensitive gas chromatographic method for the determination of cyclophosphamide in urine is presented. After liquid—liquid extraction with diethyl ether and derivatization with trifluoroacetic anhydride, cyclophosphamide was identified and quantified with mass spectrometry. The method is suitable for the determination of cyclophosphamide at concentrations of more than 0.25 ng/ml, which enables the uptake of cyclophosphamide during occupational activities, such as the preparation and administration of antineoplastic agents in hospitals, to be measured. Simple preparation makes the method appropriate for routine analysis.