bluuebunny/crossref_metadata_2025_split huggingface dataset:
Irinotecan: a new treatment in metastatic colorectal cancer
Authors: Douillard Jean-Yves 
Published: January 2007

Objective. Historically, outcomes of metastatic colorectal cancer therapy have been disappointing, with fluorouracil (5-FU) producing response rates of no more than 15%. The addition of leucovorin increases response rates; however, survival rates are largely unaffected. Recently, the topoisomerase I inhibitor, irinotecan, has proved active in metastatic colorectal cancer and is indicated as second-line therapy following disease recurrence or progression after 5-FU-based therapy. More recently, irinotecan plus 5-FU-LV was compared with 5-FU-LV as first line treatment of colorectal cancer, showing impressive results. This article discusses the role of irinotecan, as a single agent and in combination with 5-FU-LV, in the treatment of advanced colorectal cancer. Data sources. A MEDLINE search was conducted using 5-fluorouracil, irinotecan, leucovorin, and metastatic colorectal cancer as primary search terms. Reference lists, bibliographies of pertinent articles, and abstracts from the American Society of Clinical Oncology and the European Society for Medical Oncology annual meetings were also identified and reviewed. Clinical literature was reviewed and analyzed. Data synthesis. Results of studies comparing irinotecan with continuos infusion 5-FU or best supportive care suggest that irinotecan is superior to either treatment as second-line therapy of metastatic colorectal cancer. Based on these study results, along with irinotecan's lack of cross-resistance with other chemotherapy agents and mechanism of action that differs from 5-FU, phase III trials evaluating the use of irinotecan in combination with 5-FU-LV as first-line treatment for advanced colorectal cancer were conducted. The results of a pivotal trial evaluating irinotecan plus 5-FU-LV in this setting show superior response rates (RRs), time to tumor progression (TTP), and median survival times (MSTs) when compared with 5-FU-LV alone. This combination represents a major advance in the treatment of metastatic colorectal cancer and should be considered the first-line treatment standard.
Introduction to taxane pharmacokinetics and pharmacodynamics
Authors: Frame David 
Published: January 2007

Objective. To compare the pharmacokinetics and pharmacodynamics of the taxanes, paclitaxel and docetaxel. Data sources. A MEDLINE search was conducted using docetaxel, dose, drug interactions, liver dysfunction, liver impairment, mechanism of action, paclitaxel, pharmacodynamics, pharmacokinetics, and schedule as search terms. Reference lists, bibliographies of pertinent articles, and abstracts from the American Society of Clinical Oncology and the American Association for Cancer Research annual meetings were also identified and reviewed. Both preclinical and clinical literature were reviewed and analyzed. Data synthesis. The taxanes, paclitaxel and docetaxel, are a novel class of antineoplastic drugs that provide notable activity, and produce high response rates but minimal side effects. These agents share a similar mechanism of action, but several important pharmacokinetic and pharmacodynamic differences exist. The higher tubulin affinity, slower efflux from cells, triphasic elimination, and prolonged drug exposure of docetaxel confer pharmacokinetic and pharmacodynamic advantages over paclitaxel. The nonlinear pharmacokinetics of paclitaxel may result in disproportionate increases in plasma concentrations and AUCs; however, several safe and effective paclitaxel regimens are currently used. Because the taxanes are metabolized extensively in the liver by cytochrome P-450 enzymes, patients with hepatic impairment have reduced total body clearance that may result in increased toxicity. Additionally, drugs that induce, inhibit, or compete with microsomal enzymes known to metabolize the taxanes, can result in clinically significant drug interactions. These pharmacokinetic differences should be carefully considered when dosing and scheduling paclitaxel or docetaxel in clinical practice.
Prospective evaluation of a policy of early discontinuation of antibiotics and discharge from hospital in children with cancer who develop fever
Authors: Wiernikowski John T. , Barr Ronald D. , Pennie Ross 
Published: January 2007

Objective. To prospectively evaluate a set of clinical care schemata that would facilitate early discontinuation of antibiotics and hospital discharge in children with cancer admitted for management of infection. Methods. Based on recent published studies identifying children with fever and neutropenia who are at ‘‘low risk’’ for infection, and studies where antibiotics were discontinued quickly in such populations. We developed a set of four clinical schemata by which children with cancer would be managed at our institution. The schemata were prospectively evaluated over a period of 15 months. Results. The schemata were evaluated in 103 consecutive admissions in 69 children with cancer, admitted for treatment of presumed infection. In 61% of cases, children could be discharged home within 5 days of admission; only 9% was re-admitted within 7 days of discharge. In 77% of cases, children could be sent home on no antibiotics; in the remaining 23%, antibiotics could be narrowed in spectrum, and the majority sent home on an oral agent. Median length of stay for the entire cohort of patients was 5 days. In children receiving prophylactic G-CSF, the use of this agent did not impact on the length of stay, the need for subsequent re-admission, or the requirement for antibiotics at time of discharge. Conclusions. Early discontinuation of antibiotics and discharge from hospital is safe, provided that the child is clinically well and afebrile. Children with a clinical or microbiologic focus can have their spectrum of coverage narrowed, and can be safely discharged on oral agents. J Oncol Pharm Practice (2001) 6, 131-137.
Cancer gene therapy update
Authors: Smith Judith A , Goldspiel Barry R 
Published: January 2007

Objective. To provide an update about gene marking and gene therapy trials in cancer patients. Data Sources. A MEDLINE search using the term “gene therapy” was conducted for the period 1985 to 1998. The reference lists from retrieved articles were reviewed. Meeting abstracts from the American Society of Clinical Oncology annual meeting (published in their proceedings) and the Annual Cancer Gene Therapy Symposium (published in Cancer Gene Therapy) that concerned gene therapy in cancer patients were also included. Data Extraction. Both authors reviewed the retrieved material and included preclinical data, case reports, and clinical trials related to gene transfer or gene therapy in cancer patients. Data Synthesis. There are several possible approaches to using gene therapy for the diagnosis and treatment of cancer and for the monitoring of cancer therapy. Exogenous genes may be used to mark cells to help better understand cancer biology or may be used directly for cancer treatment. Gene-marking trials have already provided new information about cancer biology and have demonstrated that reinfused progenitor cells may be a source of relapse in patients with acute or chronic myelogenous leukemia and neuroblastoma. Approaches using gene therapy for cancer treatment include: using lymphocytes as gene carriers, using foreign genes to increase tumor immunogenicity, introducing tumor regression antigen genes into viruses, introducing “sensitivity” genes to produce new cytotoxic agent(s) within tumors, producing new protein product(s) to protect normal cells, replacing missing or mutant tumor suppressor genes, and inactivating oncogenes. Clinical trials using these strategies have demonstrated that gene transfer is feasible (albeit with low transduction efficiency) and that gene expression occurs; in addition, clinical responses have been noted.
Response and prediction of response to recombinant human erythropoietin in patients with solid tumors and platinum-associated anemia
Authors: Fjornes Tom 
Published: January 2007

Objective. Anemia is commonly observed in tumor patients and may be worsened by the concomitant administration of chemotherapy with platinum. Recombinant human erythropoietin (rhEPO) is able to improve the chemotherapy-associated anemia and the quality of life in patients with solid tumors. The most effective dose, route, and frequency of administration of rhEPO in anemic cancer patients has not yet been determined. The purpose of this review is to describe the results obtained up to now concerning the response and prediction of response to rhEPO in anemic patients with solid tumors undergoing platinum-based chemotherapy. In particular, the renal function conditions in this patient group were examined. Data sources. The literature was reviewed through a MEDLINE search covering 1987 to 1997. Relevant articles were additionally obtained by the systematic examination of article references. We searched the following terms: rhEPO, tumor, anemia, cisplatin, carboplatin, and renal failure. Study Selection. The current literature was reviewed with regard to both the pathophysiology of platinum-induced anemia and the clinical use, indications, and dosage of rhEPO in anemic tumor patients undergoing platinum therapy. Particular attention was directed to the prediction criteria of this drug. Conclusions. The rhEPO response rates in patients with solid tumors and platinum-associated anemia vary widely in the current literature and range from 36% to 82%. Unfortunately, no strong predictor of response can be recommended at the present time. Clinical studies support findings concerning a reduction in renal function parameters and a blunted erythropoietin response in patients with platinum-induced anemia. It is possible that a baseline serum erythropoietin concentration in conjunction with the serum creatinine concentration or the creatinine clearance value can serve as a prognostic indicator for rhEPO therapy response in this patient group.
Treatment of hormone-refractory prostate cancer
Authors: Medina Patrick J , DiPaola Robert S , Goodin Susan 
Published: January 2007

Objective. An increasing number of patients with prostate cancer develop hormone-refractory disease after standard treatment modalities. In these patients, early clinical trials with chemotherapy produced disappointing response rates. However, clinical trials that employ response criteria such as prostate-specific antigen (PSA) and clinical benefit response have produced encouraging responses. This article reviews current and future treatment options for the management of hormone-refractory prostate cancer. Data Sources. A MEDLINE search for the years 1978 to 1998 was completed. The following terms were used in our search: prostate cancer, hormone-refractory, treatment, and chemotherapy. Relevant articles referenced in the literature obtained in our MEDLINE search were reviewed. Study Selection. Randomized and nonrandomized clinical trials were used in our review. Clinical trials using prostate-specific antigen or a palliation of symptoms as primary criteria for response were given priority. Data Synthesis. Several genetic alterations, including the overexpression of bcl-2 or mutations in p53, may lead to the development of hormone-refractory prostate cancer. Agents such as estramustine and taxanes, which affect microtubule function and potentially modulate bcl-2, appear to be particularly active in the treatment of hormone-refractory prostate cancer. In addition, mitoxantrone as well as other agents has been shown to be beneficial in improving the quality of life in patients with hormone-refractory prostate cancer. Conclusion. Hormone-refractory prostate cancer is not a chemotherapy-resistant disease as once believed; significant progress in the treatment of hormone-refractory prostate cancer has been made with new combinations of chemotherapy agents. Promising new treatments are currently under evaluation to assess their potential benefit over the standard treatment modalities that are currently available.
Clinical pharmacy services in oncology clinics
Authors: Wong Shirley W , Gray Elizabeth S 
Published: January 2007

Objective. To describe the implementation and evaluation of clinical pharmacy services in ambulatory hematology-oncology clinics. Design. A prospective study was conducted to evaluate the impact of the clinical pharmacist in outpatient clinics. Setting. The clinical pharmacist is available to patients and health care professionals for drug consultations in adult hematology-oncology, cancer pain, surgical oncology, pediatric hematology-oncology, and gastrointestinal tumor clinics. The pharmacist also participates in a cancer outreach program in an off-site rural clinic. Interventions. A chart review, pharmacy patient profile review, and patient interview were performed to obtain medication histories. Drug-related problems were identified, resulting in interventions. Patient outcomes were evaluated by follow-up phone calls or by patient interviews on the following clinic visit. Results. A total of 211 interventions were documented within 36 days. The most frequent activity was patient counseling followed by therapeutic recommendations. A majority of the interventions were not related to chemotherapy. The physician acceptance rate was 94.5%. Most of the problems were of high and moderate clinical significance, with positive clinical outcomes after pharmacy interventions. Conclusion. Hematology-oncology clinics provide an excellent opportunity to involve pharmacists. A clinical pharmacist has a significant role in outpatient clinics and can potentially lead to an overall decrease in health care costs and to an improvement of the quality of patient care.
Stability of topotecan infusion solutions in polyvinylchloride bags and elastomeric portable infusion devices
Authors: Krämer Irene , Thiesen Judith 
Published: January 2007

Purpose. The purpose of this study was to determine the physicochemical stability of topotecan after reconstitution and after further dilution in two commonly used infusion fluids (0.9% sodium chloride, 5% dextrose) in both polyvinylchloride (PVC) bags and elastomeric portable infusion devices. Methods. Each vial of topotecan (Hycamtin®) was reconstituted with sterile water for injection, yielding a nominal concentration of 1 mg/mL. Topotecan infusion solutions were aseptically prepared by further dilution of reconstituted topotecan solutions with either 0.9% sodium chloride or 5% dextrose in both PVC bags and portable elastomeric infusion devices, in amounts yielding topotecan concentrations of 10 µg/mL, 25 µg/mL, or 50 µg/mL. Test solutions were stored light-protected at room temperature (25°C) or under refrigeration (2-8°C) in parallel. One test solution of the nominal concentration of 10 µg/mL topotecan in a 0.9% sodium chloride PVC infusion bag was stored under ambient light conditions (mixed daylight and normal laboratory fluorescent light) at room temperature. Topotecan concentrations were obtained periodically throughout a 4-week storage period via a stability-indicating high performance liquid chromatography assay with ultra-violet detection. In addition, measurements of pH values were performed regularly, and test solutions were visually examined for colour change and precipitation. Results. The stability tests revealed that the currently available topotecan formulation is stable (at a level of ≥90% topotecan) after reconstitution and dilution, independent of temperature (refrigerated, room temperature), the vehicle (0.9% sodium chlo-ride, 5% dextrose), the concentration (10 µg/mL, 25 µg/mL, or 50 µg/mL), or the container material (PVC bags, elastomeric portable infusion devices). The results were obtained over a test period of ≥4 weeks. Topotecan infusion solutions exposed to daylight were stable for only 17 days. Conclusions. Reconstituted and diluted topotecan infusion solutions are shown to be physicochemically stable for 4 weeks. Light protection during administration is not necessary.
Targeted toxins
Authors: Brok M W J den , de Gast G C , Schellens J H M , Beijnen J H 
Published: January 2007

Objective. Current modalities used in the treatment of cancer often cause unacceptable damage to normal tissue. Toxins targeted toward tumor cells by antibodies or growth factors have the potential to selectively kill tumor cells while leaving normal tissue intact. The purpose of this review is to provide background information on targeted toxins and current clinical studies for this new class of anti-cancer compounds. Data sources. A MEDLINE search was conducted using the term “immunotoxins.” Relevant articles were also obtained by the systematic examination of article references. Data synthesis. The toxins Pseudomonas exotoxin, diphtheria toxin, and ricin toxin are often used as targeted toxins. Deletion or mutation of the binding domains of these toxins decreased binding of the toxins to normal tissues. Antibodies or growth factors can be used as targeting moiety, and the resulting agents are called immunotoxins or fusion proteins, respectively. DNA technology and chemical modifications of the toxin as well as the antibody moiety led to smaller and less immunogenic targeted toxins. Smaller targeted toxins are less toxic and penetrate further into the tumor. The summary of several targeted toxins elicited during clinical trials in this review makes it clear that several targeted toxins are potential agents for the treatment of various cancers, although some problems still need to be overcome. These problems include toxicity, immunogenicity, cross-reactivity of the targeted toxin with life-sustaining tissue, heterogenicity of tumor cells, and limited tumor penetration.
Thalidomide does not interfere with graft-versus-leukemia reactivity in mice
Authors: Kapelushnik Joseph , Weiss Lola , Pappo Orit , Okon Eliezer , Or Reuven 
Published: January 2007

Objective. To determine whether thalidomide is an effective prophylactic agent against acute graft-versus-host disease (GVHD) and whether it exerts an effect on graft-versus-leukemia (GVL) reactivity, the drug was administered to leukemic mice that were exposed to allogeneic bone marrow transplantation. Methods. Mice (BALB/c 3 C57BL/6) F1 were inoculated with 107 B cell leukemia cells (BCL1) and conditioned with total body irradiation followed by reconstitution with bone marrow plus splenic cells harvested from C57BL/6 mice. After transplant, mice were treated with oral thalidomide (20 mg/kg/day) for a period of 10 days. Results. Stable chimerism was documented in all recipients with $73% (mean) donor-type C57 cells. In this semi-allogeneic murine model, thalidomide failed to prevent or alleviate the acute GVHD symptoms; however, the drug did not impair GVL reactivity. The antileukemia allogeneic effect was similar in the thalidomide and non-thalidomide-treated animals. Comparison of the GVL reactivity occurring in the allogeneically transplanted groups with that in the syngeneic recipients revealed a significant difference ( P 5 0.001). Conclusions. Although thalidomide did not exert any effect against acute GVHD, the fact that the GVL reactivity was spared holds promise for its use as a treatment modality in chronic GVHD.
Negative impact of cardiac evaluation before vascular surgery
Authors: Krupski William C , Nehler Mark R , Whitehill Thomas A , Lawson Robert C , Strecker Pamela K , Hiatt William R 
Published: January 2007

The optimal preoperative evaluation of cardiac risk in patients with peripheral vascular disease is controversial. In developing a paradigm for preoperative cardiac workup, potential adverse effects of evaluation and cardiac intervention must be considered. This study analyzed the deleterious outcomes of extensive, comprehensive cardiac evaluation and intervention before planned vascular surgery in patients treated at the Denver Department of Veterans Affairs Medical Center. Over a 12-month period between 1994 and 1995, 161 patients were scheduled to undergo major vascular operations; 153 patients came to operation. The decision to pursue a cardiac evaluation was variously made by a combination of surgeons, cardiologists, and anesthesiologists. No defined protocol was followed. Cardiac history, chest X-rays and ECGs were obtained for all patients. Extendedcardiac evaluation included these studies plus special tests, including echocardiography (echo), radionuclide ventriculography (RNVG), dipyridamole thallium scintigraphy (DTS), and cardiac catheterization (CC). Extended cardiac evaluations were undertaken in 42 patients. Complications related to percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG) were also recorded. Cardiac mortality and morbidity after vascular interventions were itemized in all 153 patients. Forty-two male patients, aged 68 6 9 years, underwent extended cardiac evaluations before planned vascular operations. The median elapsed time for cardiac workup was 14 days (mean 30 6 59 days). The median and mean times from cardiac workup to vascular surgery were 25 days and 76 6 142 days, respectively. Eighteen (43%) patients had echo or RNVG; 22 (52%) patients had DTS; 27 (64%) had CC; 9 (21%) had PTCA; 7 (17%) had CABG. Sixteen (38%) patients had untoward events related to cardiac evaluation. Eight patients (19%: one with cerebrovascular disease, and seven with aortic aneurysms) refused vascular surgery after extended cardiac workup. Complications attributable to CC, PTCA, and CABG included prosthetic graft infection, pseudoaneurysms (two), sternal wound infections (two), renal failure and brain anoxia. Two patients with severe limb ischemia who were candidates for revascularization ultimately required amputations because of delay due to cardiac evaluations. Extensive cardiac evaluation prior to vascular operations can result in morbidity, delays, and refusal to undergo vascular surgery. The underlying indication for vascular operations and the local iatrogenic cardiac complication rates must be considered before ordering special studies.
Vascular endothelial growth factor is efficiently synthesized in spite of low transfection efficiency of pSG5VEGF plasmids in vascular smooth muscle cells
Authors: Dulak Jozef , Józkowicz Alicja , Ratajska Anna , Szuba Andrzej , Cooke John P , Dembińska-Kieć Aldona 
Published: January 2007

The limitation of lipotransfection with plasmid vectors is its low efficiency and the short-term expression of introduced genes. This is particularly important when the synthesis of high amounts of therapeutic products is required. However, growth factors with paracrine action overcome this problem. The aim of our study was to check whether the amounts of vascular endothelial growth factor (VEGF) generated after plasmid lipotransfection into vascular smooth muscle cells (VSMC) can be sufficient to stimulate endothelial cell proliferation. Two plasmids, pSG5-VEGF121 and pSG5-VEGF165, harboring human VEGF121 and VEGF165 iso-forms were constructed and lipotransfected into COS-7 cells or to rat VSMC. The transfection efficiency, estimated by the expression of control, b-galactosidase gene, was about 50% in COS- 7 but rarely exceeded 5% in VSMC. However, despite this, the smooth muscle cells generated high amounts of VEGF protein, up to 3 ng/ml medium. The biological activity of this VEGF was confirmed by enhanced proliferation of human umbilical vein and coronary artery endothelial cells, stimulated with conditioned media of pSG5-VEGF transfected cells. Thus, the low transfection efficiency does not preclude the generation of high amounts of VEGF by VSMC. After reaching the maximum at about 48 h after transfection, the generation of VEGF decreased in the following days. Such a situation may be sufficient for the gene therapy of restenosis when the long-term expression of therapeutic gene(s) is not necessary. Thus, we suggest that the pSG5-VEGF121 and pSG5-VEGF165 plasmids can be used for therapeutic application.