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Minimal Toxicity (minimal + toxicity)
Selected AbstractsBasic principles of radiotherapy in ophtalmic oncologyACTA OPHTHALMOLOGICA, Issue 2009R DENDALE Ophtalmologic Radiation Oncology concerns intra ocular tumors, orbital tumors and eyelid tumors. In these locations, tumors are often close to normal critical tissues, increasing the risk of radiation toxicities. Basic principles of ophthalmic radiotherapy are not really different from radiotherapy of others organs. They are based on a precise description of the tumor volume, knowledge of potential tumor local or regional extension, knowledge of tissue biological radiosensitivity for tumors and the surrounding normal tissues. Based on these features, treatment modalities (radiation treatment length and fractionation) are determined to fulfill the aims of medical curative intents: good local control with acceptable toxicities or the aims of medical palliative intents: to relief with minimal toxicities. Many types of radiation therapy can be used for ophthalmic tumors: brachytherapy, orthovoltage radiotherapy, conformal therapy with photons and electrons including intensity modulated radiation therapy, protontherapy, and the use of specific devices such as CyberKnife and Tomotherapy. All of these techniques have their advantages and their disadvantages, leading the radiation oncologist to make a choice depending on the tumor site and characteristics. [source] Topical Antibacterial Agents for Wound Care: A PrimerDERMATOLOGIC SURGERY, Issue 6 2003Candace Thornton Spann MD Although often overlooked, topical antibiotic agents play an important role in dermatology. Their many uses include prophylaxis against cutaneous infections, treatment of minor wounds and infections, and elimination of nasal carriage of Stapylococcus aureus. For these indications, they are advantageous over their systemic counterparts because they deliver a higher concentration of medication directly to the desired area and are less frequently implicated in causing bacterial resistance. The ideal topical antibiotic has a broad spectrum of activity, has persistent antibacterial effects, and has minimal toxicity or incidence of allergy. [source] Concomitant low-dose cisplatin and three-dimensional conformal radiotherapy for locally advanced squamous cell carcinoma of the head and neck: Analysis of survival and toxicity,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 3 2006Harold Lau MD Abstract Background. Our center sought to implement a simple chemoradiotherapy schedule for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) with minimal toxicity to achieve rates of overall survival comparable to other schedules. Methods. The chemoradiotherapy schedule consisted of daily radiation to 70 Gy over 7 weeks with concurrent cisplatin 20 mg/m2 during days 1 to 4 of weeks 1 and 5. Acute and late toxicities were recorded according to the Radiation Therapy Oncology Group (RTOG) and common toxicity criteria (CTC) grading. The overall, disease-specific, and locoregional recurrence,free survival were calculated using the STATA statistics package. Possible factors influencing these endpoints were analyzed. Results. Fifty-seven patients were treated, and 56 patients were evaluable for follow-up. Median follow-up of alive patients was 16.1 months. There was an 82% complete response rate to chemoradiotherapy. The 2-year Kaplan,Meier overall, disease-specific, and locoregional recurrence,free survival rates were 62%, 67%, and 63%. Acute grade 3 and 4 radiation toxicity was noted in 61% and 2%, respectively. Grade 3 or 4 hematologic toxicity was noted in 7% of patients. Factors influencing overall survival included: Karnofsky performance status, receiving more than 50% of planned chemotherapy, age, and initial hemoglobin level. Conclusion. This regimen is tolerable and achieves overall survival and locoregional control rates comparable to other chemoradiotherapy schedules. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source] RT08 Population PK and PK/PD investigations and Monte Carlo simulations for a rational dosage regimenJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2006P. L. TOUTAIN Objective There are several means whereby dosage schedules for clinical use may be set, some more appropriate and scientific than others! The challenge of the 21st century must be for colleagues in the pharmaceutical industry, those serving registration bodies and academic colleagues to pool their expertise with the objective of designing dosage schedules for clinical use, which are based on the application of sound scientific principles appropriate for each drug class. In this Roundtable Session colleagues of international standing will review (a) pharmacological and other sources of variability in the responses to drugs; (b) the advantages and limitations of pre-clinical studies for dose selection; (c) the roles of population PK and population PK/PD together with Monte Carlo simulations in dosage regimen selection; (d) Bayesian approaches to dosage selection and (e) regulatory guidelines on the type and extent of studies required for selecting dosages. There is no unanimity amongst stakeholders on either the principles or the methods underlying dosage schedule design. Dose titration studies have long been the principal means of fixing doses but PK-PD and population PK-PD studies are now challenging more traditional approaches. The papers and discussion in this Roundtable Session will provide a critical basis for future advances in this crucial area of therapeutic drug usage. Getting the doses right means that the patient will receive maximum benefit, in terms of optimal efficacy with minimal toxicity, and hence correct dosing will contribute enormously to animal welfare. [source] RT09 Bayesian approaches in dosage selectionJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2006D. CONCORDET Objective There are several means whereby dosage schedules for clinical use may be set, some more appropriate and scientific than others! The challenge of the 21st century must be for colleagues in the pharmaceutical industry, those serving registration bodies and academic colleagues to pool their expertise with the objective of designing dosage schedules for clinical use, which are based on the application of sound scientific principles appropriate for each drug class. In this Roundtable Session colleagues of international standing will review (a) pharmacological and other sources of variability in the responses to drugs; (b) the advantages and limitations of pre-clinical studies for dose selection; (c) the roles of population PK and population PK/PD together with Monte Carlo simulations in dosage regimen selection; (d) Bayesian approaches to dosage selection and (e) regulatory guidelines on the type and extent of studies required for selecting dosages. There is no unanimity amongst stakeholders on either the principles or the methods underlying dosage schedule design. Dose titration studies have long been the principal means of fixing doses but PK-PD and population PK-PD studies are now challenging more traditional approaches. The papers and discussion in this Roundtable Session will provide a critical basis for future advances in this crucial area of therapeutic drug usage. Getting the doses right means that the patient will receive maximum benefit, in terms of optimal efficacy with minimal toxicity, and hence correct dosing will contribute enormously to animal welfare. [source] Neopterin in renal cell carcinoma: inhalational administration of interleukin-2 is not accompanied by a rise of urinary neopterinLUMINESCENCE: THE JOURNAL OF BIOLOGICAL AND CHEMICAL LUMINESCENCE, Issue 4-5 2005Bohuslav Melichar Abstract Inhalational administration of interleukin-2 (IL-2) is effective in controlling renal cell carcinoma (RCC) lung metastases with minimal toxicity. Neopterin is an indicator of systemic immune activation in metastatic cancer and is increased after systemic IL-2 administration. Urinary neopterin was investigated in 13 patients with metastatic RCC and 18 controls. In seven patients, urinary neopterin was followed before and after treatment with inhalational IL-2. Neopterin was measured by highperformance liquid chromatography and creatinine was determined by Jaffé reaction. Urinary neopterin was significantly increased in patients with metastatic RCC compared to controls (257 ± 263 µmol/mol creatinine vs. 110 ± 41 µmol/mol creatinine; Mann,Whitney U-test, p < 0.05). Median survival was significantly longer in patients with urinary neopterin <173 µmol/mol creatinine compared to patients with neopterin ,173 µmol/mol creatinine (698 vs. 245 days; log-rank test, p < 0.05). No significant increase was observed after inhalational IL-2 therapy (147 ± 101 vs. 153 ± 54 µmol/mol creatinine). We conclude that urinary neopterin is increased in patients with metastatic RCC, and higher neopterin concentrations are indicative of poor prognosis. The absence of an increase in urinary neopterin after inhalational IL-2 therapy is in accord with the lack of significant systemic toxicity. Copyright © 2005 John Wiley & Sons, Ltd. [source] Review: On TRAIL for malignant glioma therapy?NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 3 2010J. M. A. Kuijlen J. M. A. Kuijlen, E. Bremer, J. J. A. Mooij, W. F. A. den Dunnen and W. Helfrich (2010) Neuropathology and Applied Neurobiology36, 168,182 On TRAIL for malignant glioma therapy? Glioblastoma (GBM) is a devastating cancer with a median survival of around 15 months. Significant advances in treatment have not been achieved yet, even with a host of new therapeutics under investigation. Therefore, the quest for a cure for GBM remains as intense as ever. Of particular interest for GBM therapy is the selective induction of apoptosis using the pro-apoptotic tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). TRAIL signals apoptosis via its two agonistic receptors TRAIL-R1 and TRAIL-R2. TRAIL is normally present as homotrimeric transmembrane protein, but can also be processed into a soluble trimeric form (sTRAIL). Recombinant sTRAIL has strong tumouricidal activity towards GBM cells, with no or minimal toxicity towards normal human cells. Unfortunately, GBM is a very heterogeneous tumour, with multiple genetically aberrant clones within one tumour. Consequently, any single agent therapy is likely to be not effective enough. However, the anti-GBM activity of TRAIL can be synergistically enhanced by a variety of conventional and novel targeted therapies, making TRAIL an ideal candidate for combinatorial strategies. Here we will, after briefly detailing the biology of TRAIL/TRAIL receptor signalling, focus on the promises and pitfalls of recombinant TRAIL as a therapeutic agent alone and in combinatorial therapeutic approaches for GBM. [source] Unrelated bone marrow transplant for congenital amegakaryocytic thrombocytopenia: Report of two cases and review of the literaturePEDIATRIC TRANSPLANTATION, Issue 4 2010Haydar Frangoul Frangoul H, Keates-Baleeiro J, Calder C, Manes B, Crossno C, Castaneda VL, Domm J. Unrelated bone marrow transplant for congenital amegakaryocytic thrombocytopenia: Report of two cases and review of the literature. Pediatr Transplantation 2010: 14:E42,E45. © 2009 John Wiley & Sons A/S. Abstract:, CAMT is a very rare cause of thrombocytopenia in infants. Most of the patients will progress to marrow failure. Allogeneic stem cell transplant remains the only curative therapy. We present two patients with CAMT who underwent an unrelated donor bone marrow transplant, one after developing marrow failure and another early in the course of the disease. Both patients tolerated the transplant with minimal toxicity and durable engraftment. We also present a comprehensive review of the literature for unrelated donor transplant for this condition. [source] Benzodiazepines in epilepsy: pharmacology and pharmacokineticsACTA NEUROLOGICA SCANDINAVICA, Issue 2 2008J. Riss Benzodiazepines (BZDs) remain important agents in the management of epilepsy. They are drugs of first choice for status epilepticus and seizures associated with post-anoxic insult and are also frequently used in the treatment of febrile, acute repetitive and alcohol withdrawal seizures. Clinical advantages of these drugs include rapid onset of action, high efficacy rates and minimal toxicity. Benzodiazepines are used in a variety of clinical situations because they have a broad spectrum of clinical activity and can be administered via several routes. Potential shortcomings of BZDs include tolerance, withdrawal symptoms, adverse events, such as cognitive impairment and sedation, and drug interactions. Benzodiazepines differ in their pharmacologic effects and pharmacokinetic profiles, which dictate how the drugs are used. Among the approximately 35 BZDs available, a select few are used for the management of seizures and epilepsy: clobazam, clonazepam, clorazepate, diazepam, lorazepam and midazolam. Among these BZDs, clorazepate has a unique profile that includes a long half-life of its active metabolite and slow onset of tolerance. Additionally, the pharmacokinetic characteristics of clorazepate (particularly the sustained-release formulation) could theoretically help minimize adverse events. However, larger, controlled studies of clorazepate are needed to further examine its role in the treatment of patients with epilepsy. [source] Investigation into the effects of cidofovir on an in vitro model of recurrent respiratory papillomatosisCLINICAL OTOLARYNGOLOGY, Issue 3 2006A.J. Donne Problem. Recurrent respiratory papillomatosis (RRP) has no cure, and cidofovir is currently the most contemporary adjuvant treatment. Cidofovir has reported activity against Human Papilloma Virus type 16, but no laboratory studies have yet been performed on HPV type 6 which is the main cause of RRP. This work describes the generation of a novel HPV 6 related cell line and its use to evaluate the effects of Cidofovir. Method. HPV6b E6 cDNA was stably introduced into HPV negative C33A cervical carcinoma cells to produce the C33AT6E6 cell line. Two different doses of Cidofovir were applied to parent C33A, C33AT6E6 and C33AT16E6 (type 16 cell line) with appropriate controls. Growth and FACS cell cycle analysis were performed after 3 and 6 days of continuous exposure followed by 2 and 3 days post-drug withdrawal. Result.PCR analysis confirmed HPV6 E6 expression in C33AT6E6 cells. High dose cidofovir was toxic at 3 and 6 days exposure in all cells tested. Low dose exposure was toxic for C33AT16E6 cells at 3 days whereas C33A and C33AT6E6 only showed minimal toxicity at 6 days. C33A and C33AT6E6 cells also showed earlier recovery following drug withdrawal. Conclusion.Cidofovir showed varying degrees of non-specific toxicity against all three cell lines tested. However, HPV16 E6 expressing cells were more sensitive than either parent or HPV6 E6 expressing cells indicating that cidofovir has no selective advantage for the RRP related HPV6 E6 expressing cell line. [source] | ||||||||||