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Related Toxicity (relate + toxicity)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer: A systematic review and meta-analysis

INTERNATIONAL JOURNAL OF CANCER, Issue 12 2009
Wim Ceelen
Abstract Combining chemotherapy with preoperative radiotherapy (RT) has a sound radiobiological rationale. We performed a systematic review and meta-analysis of trials comparing preoperative RT with preoperative chemoradiation (CRT) in rectal cancer patients. The Cochrane Central Register of Controlled Trials, Web of Science, Embase and Medline (Pubmed) were searched from 1975 until June 2007. Dichotomous parameters were summarized using the odds ratio while time to event data were analyzed using the pooled hazard ratio for death. From the primary search result of 324 trials, 4 relevant randomized trials were identified. The addition of chemotherapy significantly increased grade III and IV acute toxicity (p = 0.002) while no differences were observed in postoperative morbidity or mortality. Preoperative CRT significantly increased the rate of pathological complete response (p < 0.001) although this did not translate into a higher sphincter preservation rate (p = 0.29). The local recurrence rate was significantly lower in the CRT group (p < 0.001). No statistically significant differences were observed in disease free survival (p = 0.89) or overall survival (p = 0.79). Compared to preoperative RT alone, preoperative CRT improves local control in rectal cancer but is associated with a more pronounced treatment related toxicity. The addition of chemotherapy does not benefit sphincter preservation rate or long-term survival. Future trials should address improvements in the rate of distant metastasis and overall survival by incorporating more active chemotherapy. © 2008 UICC [source]

Predictors of Toxicity and Toxicity Profile of Adjuvant Chemotherapy in Elderly Breast Cancer Patients

THE BREAST JOURNAL, Issue 4 2009
Praveen Garg MD
Abstract:, Women older than 70 years have been underrepresented in breast cancer adjuvant chemotherapy trials due to concerns about toxicity, safety and tolerance of chemotherapy. The aim of our study was to assess the tolerance of chemotherapy in older women with breast cancer and determine patterns of toxicity including the impact of age, chemotherapy regimen, functional status and comorbid conditions on this toxicity. We retrospectively reviewed the charts of early stage (stages 1 and 2) breast cancer patients older than 70 years from 1998 to 2004. A total of 62 patients, with mean age of 74.3 years, were identified. Chemotherapy was completed in 89% patients. Overall 79% completed chemotherapy without any significant side-effects, dose reductions, or breaks during chemotherapy. Using logistic regression model increasing age was not associated with early termination of chemotherapy (p = 0.19, OR: 0.868, 95% CI: 0.7,1.076). However, increasing age, lower functional status, and higher comorbidity index scores were associated with reduction in dose and breaks in chemotherapy. None of the patients who received pegfilgrastim prophylactically developed high-grade neutropenia. Our study suggests that adjuvant chemotherapy is safe in elderly patients. Older patients with good functional status and low comorbidity index scores tolerate chemotherapy as well as the younger patients. Prophylactic use of pegfilgrastim may reduce occurrence of severe neutropenia and related toxicity such as febrile neutropenia in the elderly patient. [source]

Evaluation of GSH adducts of adrenaline in biological samples

BIOMEDICAL CHROMATOGRAPHY, Issue 7 2007
Renata Silva
Abstract The sustained high release of catecholamines to circulation is a deleterious condition that may induce toxicity, which seems to be partially related to the products formed by oxidation of catecholamines that can be further conjugated with glutathione (GSH). The aim of the present study was to develop a method for the determination of GSH adducts of adrenaline in biological samples. Two position isomers of the glutathion-S-yl-adrenaline were synthesized and characterized by HPLC using diode array, coulometric and mass detectors. A method for the extraction of these adducts from human plasma was also developed, based on adsorption to activated alumina, which showed adequate recoveries and proved to be crucial in removing interferences from plasma. The selectivity, precision and linearity of the method were all within the accepted values for these parameters. Furthermore, the sensitivity of this method allows the detection of adduct amounts that are within the range of the expected concentrations for these adducts under certain pathophysiological conditions and/or drug treatments. In conclusion, the development of this method allows the direct analysis of GSH adducts of adrenaline in human plasma, providing a valuable tool for the study of the catecholamine oxidation process and its related toxicity. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Raloxifene, an oestrogen-receptor-,-targeted therapy, inhibits androgen-independent prostate cancer growth: results from preclinical studies and a pilot phase II clinical trial

BJU INTERNATIONAL, Issue 4 2006
RONALD L. SHAZER
OBJECTIVES To determine, in preclinical in vivo animal and in clinical studies, whether raloxifene (a selective oestrogen-receptor (ER) modulator that targets ER-, and induces apoptosis in vitro in androgen-independent prostate cancer, AIPC cells) affects prostate cell differentiation, proliferation and carcinogenesis, and in the pilot phase II clinical trial, the response rate and duration of patients with AIPC treated with a daily oral dose of raloxifene. PATIENTS, MATERIALS AND METHODS Tumour proliferation rate in response to raloxifene treatment, and molecular markers of cell cycle and apoptosis, were evaluated in established ER-,-positive androgen-dependent (AD) CWR22 and AI CWRSA9 human xenograft prostate cancer models. Twenty-one patients with AIPC and evidence of disease progression were enrolled into the clinical trial and given daily oral raloxifene. RESULTS There was significant growth inhibition by raloxifene in the ADPC and AIPC xenograft models (CWR22 68%, P < 0.010; CWRSA9 64%, P < 0.001), with no tumour regression. There was evidence of G1 arrest by increased p27kip1 expression in the raloxifene-treated group. Eighteen patients comprised the efficacy analysis, as three withdrew before the first evaluation. At the first evaluation, five men had stable disease and continued on the study for a median of five cycles. The longest response was 17 cycles. Drug related toxicity was minimal. CONCLUSION Raloxifene has activity in xenograft models, slowing disease progression. This translated to possible disease stabilization in patients with AIPC. Further studies are warranted. [source]