[Extracapsular Proximal Femoral Fractures - Retrospective Evaluation of a Group of Patients with a Focus on Complications of Treatment]. / Extrakapsulární zlomeniny proximálního femuru ­ retrospektivní vyhodnocení souboru pacientu se zamerením na komplikace lécby.

PURPOSE OF THE STUDY The purpose of this study is to retrospectively evaluate the treatment and the complications in patients with extracapsular proximal femoral fractures. MATERIAL AND METHODS The evaluation focused on a group of patients who underwent a surgery at the authors department in the period from 1 January 2011 to 31 December 2013. The inclusion criteria were a simple fall and a monotrauma. The injury-to-surgery interval, course of the surgery and hospital stay, occurrence of early and late complications were assessed. RESULTS In the respective period 286 patients underwent surgery, with the mean age of 79 years (36-101). A basicervical fracture was suffered by 20 patients, a pertrochanteric fracture by 228 patients and 38 patients sustained a subtrochanteric fracture. Osteosynthesis using the DHS was applied in 113 patients, in 110 patients PFNA osteosynthesis was performed and in 51 patients osteosynthesis using an Ender nail was conducted. Yet another type of plate osteosynthesis was opted for in 12 patients. The most frequent postoperative complication was delirium, which was reported in a total of 38 patients. Non-infectious early seroma and hematoma type collection was observed in 6 patients. An infection occurred in one patient. Apart from 8 patients who died during the primary hospital stay, the fracture healing was followed up in 252 patients (91% of 278). The length of healing was 15 weeks on average, delayed healing was reported in five patients. Primary malposition was seen in 9 patients (3%) and secondary malposition occurred in five patients (2%). There were five cases of non-union (2% of 278) in our group of patients. In the followed-up period, a total of 86 patients (30 % of 286) died within one year after the injury. In cases of death, the follow-up was 100% thanks to the data obtained from the Institute of Health Information and Statistics of the Czech Republic (UZIS). Death as a direct consequence of proximal femur fracture occurred in 66 patients (23% of 286). DISCUSSION The results of complications in our group (infection, delayed healing, malposition and non-union) are comparable to those identified by other authors, with the exception of one-year lethality, which is lower in the presented group. CONCLUSIONS The occurrence of complications after proximal femur surgeries is affected by multiple factors. The most important are the choice of a suitable implant, technically correct execution of osteosynthesis and intensive postoperative treatment, including the continuity of care after hospital discharge. Key words:extracapsular proximal femoral fractures, complications.

QOL and Survival Comparisons by Race in Oncology Clinical Trials.

BACKGROUND: Significant efforts have been made to increase access and accrual to clinical trials for minority cancer patients (MP). This meta-analysis looked for differences in survival and baseline quality of life (QOL) between MP and non-minority cancer patients (NMP). MATERIALS AND METHODS: Baseline QOL and overall survival times from 47 clinical trials (6513 patients) conducted at Mayo Clinic Cancer Center/North Central Cancer Treatment Group were utilized. Assessments included Uniscale, Linear Analogue Self Assessment, Symptom Distress Scale (SDS), Profile of Mood States and Functional Assessment of Cancer Therapy - General, each transformed into a 0-100 scale with higher scores indicating better outcomes. This transformation involves subtracting the lowest possible value from the assessment, dividing by the range of the scale (the maximum minus the minimum), and multiplying by 100. Analyses included Fisher's Exact tests, linear regression, Kaplan-Meier curves, and Cox proportional hazards models. RESULTS: Eight percent of patients self-reported as MP (0.45% American Indian/Alaskan Native, 0.7% Asian, 5% Black/African American, 1.5% Hispanic, 0.1% Native Hawaiian and 0.3% Other). MP had no meaningful deficits relative to non-MP in overall QOL but were slightly worse on FACT-G total score, physical, social/family, functional, and SDS nausea severity. MP with lung, neurological or GI cancers had significantly worse mean scores in nausea (58 vs. 69), sleep problems (34 vs. 54); emotional (53 vs. 74); and social/family (60 vs. 67), respectively. Regression models confirmed these results. After adjusting for disease site, there were no significant differences in survival. CONCLUSION: MP on these clinical trials indicated small deficits in physical, social, and emotional subscales at baseline compared to NMP. Within cancer sites, MP experienced large deficits for selected QOL domains that bear further attention.

[Impaired Healing after Surgery for Femoral Fractures]. / Poruchy hojení po operacní lécbe zlomenin stehenní kosti.

PURPOSE OF THE STUDY: The aim of the study was to analyse causes of impaired bone healing in femoral fractures and to present options of their management. MATERIAL AND METHODS: This is a retrospective study of the data on complications prospectively collected between 2008 and 2013. The patients admitted for primary treatment at the Trauma Centre of the Faculty of Medicine in Hradec Kralove from January 2008 to December 2013 included 1186 patients with injury severity scores (ISS) > 15 and 1340 patients with new injury severity scores (NISS) >15, all older than 16 years. With the exception of two patients, the primary treatment involved the application of an external fixator as part of damage control surgery. Definitive surgery, regardless of the site of fracture, was performed using unreamed femoral nails (UFN) in 51, distal femoral nails (DFN) in 33, plates in 26, long proximal femoral nail antirotation (PFNA-long) in 14 and nails combined with dynamic hip screw (DHS) plates in five fractures. The analysis revealed both mechanical and biological causes of poor bone healing. RESULTS: Of the 124 patients whose multiple injuries included a fracture of the femur, 11 died within 24 hours in spite of intensive resuscitation. In the remaining 113 patients there were 16 bilateral fractures, 20 fractures of the proximal femur (extraarticular), 72 diaphyseal femur fractures and 26 distal femur fractures. Nine patients sustained segmental femoral shaft fractures. Ten diaphyseal and 14 distal femur injuries were open fractures (13.5% and 54%, respectively). Pseudarthrosis developed in a total of 12 fractures (9.3%); six (7.2%) were diaphyseal fractures, of which three were initially open fractures, and six (21.4%) were distal femur fractures with two initially open injuries. All proximal femur fractures healed completely. DISCUSSION: The frequency of non-union femoral diaphyseal fractures in our patients treated by unreamed intra-medullary nailing is in agreement with the literature data. The frequency of non-union distal femur fractures in our group was slightly higher than is published in the literature. This can be accounted for by the characteristics of our group consisting of patients with multiple severe injuries in whom fractures are due to high-energy trauma; the overall severity of injuries negatively affects the biological potential of a human organism for bone healing. CONCLUSIONS: A successful outcome of femoral fracture repair is based on an understanding of the biomechanical principle, i.e., correct fracture reduction and stable osteosynthesis fitting the morphology of the fracture. Comminuted femoral fractures heal well with the use of a narrow long nail whose working length allows for even distribution of movement at a fracture line amongst the fragments and thus fracture motion load does not exceed 20%. On the other hand, short oblique and transverse fractures are examples of problematic fractures which require maximum possible stability provided by a thick nail with a short working length; this is achieved by reaming the medullary cavity or adding lag screws. In our group of patients these fractures were also the most problematic ones. Generally, nailing remains the golden standard in the management of femoral fractures.

Disease-free ovarian cancer patients report severe pain and fatigue over time: prospective quality of life assessment in a consecutive series.

UNLABELLED: objective: Among ovarian cancer patients, cancer treatment is aggressive and yet survival is often so limited; hence, this study sought to measure quality of life with the ultimate goal of identifying ways of improving it over the duration of these patients' lives. MATERIALS AND METHODS: The medical records of all ovarian cancer patients who received some/all of their initial chemotherapy at the Mayo Clinic in Rochester, Minnesota from late 2010 through 2012 were reviewed. Patient-reported quality of life was derived from the following ten-point linear analogue scale questions which had been administered to all patients: 1) How would you describe your degree of pain, on average? 2) How would you describe your level of fatigue, on average? 3) How would you describe your overall quality of life? Quality of life data were censored upon cancer recurrence. RESULTS: Among 59 eligible patients, the median cumulative interval during which quality of life was serially assessed was 1.15 years (range: three months, 3.2 years). Area under the curve for pain, fatigue, and global quality of life showed no statistically significant differences between patients treated with dose-dense chemotherapy with carboplatin/paclitaxel (n = 10) versus three-week chemotherapy with carboplatin/paclitaxel (n = 36) versus other (n = 13). Although pain, fatigue, and global quality of life improved over time, 35 of 59 (59%) patients reported grade 4 or worse pain during follow up, and 47 of 59 (80%) reported grade 4 or worse fatigue (higher scores denote worse pain or fatigue). After completion of cancer treatment, 30 (51%) described grade 4 or worse pain or fatigue. The most common pain site was the abdomen/pelvis, followed by the back, followed by the hands, feet, fingers, and toes. CONCLUSION: In ovarian cancer patients who remain cancer-free, severe pain and fatigue occur years after cancer treatment. Further research should focus on how best to address these symptoms.

Endpoint comparison for bone mineral density measurements in North Central Cancer Treatment Group cancer clinical trials N02C1 and N03CC (Alliance).

UNLABELLED: Bone mineral density (BMD) measurement can vary depending upon anatomical site, machine, and normative values used. This analysis compared different BMD endpoints in two clinical trials. Trial results differed across endpoints. Future clinical trials should consider inclusion of multiple endpoints in sensitivity analysis to ensure sound overall study conclusions. INTRODUCTION: Methodological issues hamper efficacy assessment of osteoporosis prevention agents in cancer survivors. Osteoporosis diagnosis can vary depending upon which bone mineral density (BMD) anatomical site and machine is used and which set of normative values are applied. This analysis compared different endpoints for osteoporosis treatment efficacy assessment in two clinical studies. METHODS: Data from North Central Cancer Treatment Group phase III clinical trials N02C1 and N03CC (Alliance) were employed involving 774 patients each comparing two treatments for osteoporosis prevention. Endpoints for three anatomical sites included raw BMD score (RawBMD); raw machine-based, sample-standardized, and reference population-standardized T scores (RawT, TSamp, TRef); and standard normal percentile corresponding to the reference population-standardized T score (TPerc). For each, treatment arm comparison was carried out using three statistical tests using change and percentage change from baseline (CB, %CB) at 1 year. RESULTS: Baseline correlations among endpoints ranged from 0.79 to 1.00. RawBMD and TPerc produced more statistically significant results (14 and 19 each out of 36 tests) compared to RawT (11/36), TSamp (8/36), and TRef (7/36). Spine produced the most statistically significant results (26/60) relative to femoral neck (20/60) and total hip (13/60). Lastly, CB resulted in 44 statistically significant results out of 90 tests, whereas %CB resulted in only 15 significant results. CONCLUSIONS: Treatment comparisons and interpretations were different across endpoints and anatomical sites. Transforming via sample statistics provided similar results as transforming via reference or machine-based norms. However, RawBMD and TPerc may be more sensitive to change as clinical trial endpoints.

[The current view of the diagnosis and management of amebiasis in the light of the authors own case reports]. / Soucasný pohled na diagnostiku a lécbu amébózy ve svetle vlastní kazuistické zkusenosti.

This comprehensive review is focused on a serious protozoan disease, amebiasis. This disease is caused by the human parasite Entamoeba histolytica (E. histolytica), the second leading cause of mortality due to protozoan disease worldwide (the leading cause is malaria). The incidence of amebiasis in the Czech Republic is very low, but it may be underreported as the disease often escapes diagnosis. Intestinal colonisation by E. histolytica may be asymptomatic. The clinical picture ranges from diarrhea to colitis or fulminant colitis when the parasite progresses to the trophozoite stage. Secondary dissemination in the blood or lymph system may induce systemic signs of the disease. Liver abscess is the most common extraintestinal form of amebiasis. The diagnosis of intestinal amebiasis is based on the clinical picture and parasitological examination of the stool. To diagnose extraintestinal amebiasis, serology tests are used to detect antibodies in the blood. Recently, molecular methods have been increasingly used for the detection of the nucleic acids of the pathogen in biological specimens. The first line therapy for amebiasis are 5-nitroimidazole drugs, currently available in the Czech Republic. However, surgical intervention should also be considered in patients with a severe course of the disease. Included in the review are the case reports of patients with severe concomitant intestinal and extraintestinal amebiasis.

[Pectoralis maior tendon rupture and anabolic steroids in anamnesis--a case review]. / Ruptura slachy m. pectoralis maior a anabolické steroidy v anamnéze--kazuistika.

INTRODUCTION: Muscle building, gaining in popularity, and availability of anabolic steroids are connected with raised incidence of tendon injuries in uncommon locations. CASE REVIEW: The author describes a case of an injured body builder treated for the major pectoral muscle's tendon rupturing, and, later on, for the quadriceps tendon and distal bicipital tendon ruptures. The m. pectoralis major tendon rupture was managed surgically-including tendon reinsertion, temporary immobilization and gradual rehabilitation with dosed loading. The treatment resulted in full recovery and the patient was able to resume common and sport activities. DISCUSSION: The study assessed the role of steroids in development of tendon injuries, as well as their treatment methods. Based on his experience, the author, as well as other authors, favours indication for early surgical management to conservative treatment.

Initially elevated osteoprotegerin serum levels may predict a perioperative myocardial lesion in patients undergoing coronary artery bypass grafting.

OBJECTIVE: We investigated whether osteoprotegerin (OPG), an important regulator in the genesis of arteriosclerosis and bone formation, is able to identify patients at risk for perioperative myocardial infarction measured as cardiac troponin I (cTNI) and signs of myocardial ischemia in the electrocardiogram after coronary artery bypass grafting (CABG). DESIGN: Observational study. SETTING: Post-surgical intensive care unit of a tertiary care center. PATIENTS: Ninety-seven patients undergoing elective CABG. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: OPG and cTNI were measured before and 24 hrs after CABG. Additionally, cTNI was measured after 12 hrs. Electrocardiography was done before and immediately after CABG. OPG before CABG (OPGpre) measurements correlated with cTNI measurements after 12 hrs (cTNI12) (r = 0.56; p < .0001) and with cTNI measurements after 24 hrs (cTNI24) (r = 0.77; p < .0001). OPGpre measurements correlated with electrocardiographic findings after surgery (r = 0.65; p < .0001). There was a positive correlation between OPGpre value and the number of bypasses (r = 0.95; p < .0001). A strong correlation was found between OPGpre and homocysteine (r = 0.96; p < .0001). The median OPG presurgical level for the four patients with cardiac complications was found to be notably elevated (28.1 [26.6/31.0] pmol/L) in comparison with that for patients without complications (10.2 [3.7/16.9] pmol/L). CONCLUSIONS: OPG appears to be a useful marker for estimating risk for perioperative myocardial infarction in patients undergoing CABG, as demonstrated by signs of ischemia on electrocardiography.

Methodologic lessons learned from hot flash studies.

PURPOSE: In the course of conducting a series of prospective clinical trials devoted to defining new treatment opportunities for hot flashes in cancer survivors, considerable experience has been acquired with related methodologic issues. This article has been written in response to many queries regarding this methodology. PATIENTS AND METHODS: A series of seven different clinical trials that involved 968 patients was used for this work. Reliable and valid definitions of hot flash intensity were developed from patient-reported descriptions. Concomitant validity and reliability assessment of patient-completed diaries was undertaken to compare hot flash data with toxicity and quality-of-life (QOL) end points and to examine consistency across patient groups using variability analysis and correlation procedures. Parametric data from this meta-analysis was used to examine relative power considerations for the design of phase II and phase III clinical trials. RESULTS: Daily diaries used in these studies exhibited consistency and reliability and had few missing data. Hot flash frequency and hot flash score (frequency multiplied by average severity) variables produced almost identical end point results. For phase III placebo-controlled studies, 50 patients per treatment arm seem appropriate to provide sufficient power specifications to detect a clinically meaningful change in hot flash activity. For phase II trials, 25 patients per trial seem to provide reasonable estimates of eventual hot flash efficacy to screen potential agents for more definitive testing. CONCLUSION: Given the data gained from these experiences, we can plan and carry out more efficient trials to identify efficacious agents for the reduction of hot flash activity.

A simple stratification factor prognostic for survival in advanced cancer: the good/bad/uncertain index.

PURPOSE: This article summarizes the third step of a research program to identify variables that supplement the predictive power of the the Eastern Cooperative Oncology Group (ECOG) performance status (PS) for survival. The objective was to produce a simple, practical, stratification factor for phase III oncology clinical trials involving patients with advanced malignant disease. PATIENTS AND METHODS: A questionnaire was administered to 729 patients with metastatic colorectal or lung cancers. Patients provided a Karnofsky index and appetite rating while physicians provided a survival estimate and the ECOG-PS. Scores for each item were categorized as having a positive, neutral, or negative indication for survival. A patient was classified as having a relatively good prognosis if three or more of the four items showed a positive indication, a bad prognosis if three or more items were negative, and an uncertain prognosis otherwise (Good/Bad/Uncertain [GBU] index). RESULTS: The GBU index improved on the prognostic power of a Cox model quartile index and PS alone and increased the accuracy of survival classification estimates by 5% to 10% more than ECOG-PS alone. For patients with PS of 0 or 1, significant survival patterns exist between GBU groups (P=.002 and.0001, respectively). CONCLUSION: The GBU index may be recommended as a supplementary stratification factor for certain future phase III trials in metastatic lung or colorectal cancer where patient heterogeneity is a particular concern. The GBU represents a relatively modest increase to the cost and patient burden of a clinical trial given the additional control that is achieved over the potentially confounding concomitant to the treatment variable.

Patients with reconstruction of craniofacial or intraoral defects: development of instruments to measure quality of life.

Patients with reconstruction of craniofacial or intraoral defects experience a profound impact on their quality of life (QOL). This impact on QOL is influenced by the patients' medical conditions and the treatment interventions. Instruments to measure general QOL have been available for many years. A major criticism of QOL instruments is that too often the questions are not specific to the particular problems of a disease or condition. A search of the literature regarding QOL measurement for patients with maxillofacial implant-supported prostheses produced a short list of instruments, none of which were sufficiently developed or suited to the patients involved in reconstructive treatment. This study was designed to develop pretreatment and posttreatment questionnaires for measuring QOL for patients with reconstruction of a craniofacial defect and patients with reconstruction of loss of specific intraoral structures utilizing an implant-supported prosthesis (e.g., severe resorption of the maxilla or mandible or both). The goal was to develop brief, targeted instruments for this specific patient population. The produced instruments were sensitive and easy to administer and score, and no disruption of clinical care occurred with the administration of the questionnaires. The instruments were used with equal success both in face-to-face interviews and via mail.

Efficacy of neuroradiological imaging, neurological examination, and symptom status in follow-up assessment of patients with high-grade gliomas.

OBJECT: It is standard practice for the oncological follow-up of patients with brain tumors (especially in the setting of clinical trials) to include neurological examination and neuroradiological studies such as computerized tomography (CT) or magnetic resonance (MR) imaging in addition to evaluation of the patients' symptomatology and performance score. The validity of this practice and its impact on the welfare of patients with high-grade gliomas has not been adequately assessed. The purpose of this study is to provide such an assessment. METHODS: The authors studied 231 similarly treated patients who were participating in three prospective North Central Cancer Treatment Group or Mayo Clinic trials who developed progressive disease during follow up. According to the protocol, the symptom status, performance score, results of neurological examination, and CT or MR status were recorded prospectively in each patient at each evaluation (every 6-8 weeks). At progression, 177 (77%) of 231 patients experienced worsening of their baseline symptoms or they developed new ones. In the remaining 54 asymptomatic patients (23%), neuroradiological imaging revealed the progression. Asymptomatic progression was more likely to be detected on MR imaging compared with CT studies (p < 0.01). In no asymptomatic patient was progression detected on neurological examination alone. The median survival time after tumor recurrence was 13.3 weeks in symptomatic patients compared with 41.7 weeks in the asymptomatic group (p < 0.0001). Asymptomatic patients were more aggressively treated, with surgery (p < 0.0001) and second-line chemotherapy (p < 0.0002). Multivariate analysis of survival time following first progression by using both classification and regression trees and Cox models showed that treatment at recurrence was the most important prognostic variable. CONCLUSIONS: Symptoms are the most frequent indicators of progression in patients with high-grade gliomas (77%). All asymptomatic progressions were detected on neuroradiological studies; MR imaging was more likely than CT scanning to reveal asymptomatic recurrences. Survival after disease progression was significantly longer in asymptomatic patients and could be related both to treatment following progression and to other favorable prognostic factors such as performance score.

A North Central Cancer Treatment Group phase II trial of topotecan in relapsed gliomas.

Current systemic treatment options for patients with relapsed gliomas are limited. The topoisomerase I inhibitor topotecan has demonstrated broad antitumor activity in both preclinical studies as well as a number of phase I and II trials in humans. Studies in primates have shown good cerebrospinal fluid levels of topotecan following systemic administration. We therefore performed this phase II trial in patients who developed evidence of progressive glioma after definitive radiation therapy. Patients were treated with 1.5 mg/m2 intravenously daily for 5 consecutive days repeated every three weeks. For patients who had received prior nitrosourea-containing chemotherapy, the starting dose was 1.25 mg/m2. Thirty-three patients were entered on this study. All patients were eligible and evaluable for both response and toxicity. Seven patients experienced grade 4 leukopenia with 2 of these patients dying of infection-related complications. Six of these seven patients were not taking anticonvulsants during treatment. Nine patients developed grade 3-4 thrombocytopenia, seven of whom were not taking anticonvulsants. Nonhematologic side effects were infrequent and manageable. One patient experienced a partial response to this treatment for an overall response rate of 3% (95% binomial confidence interval 0.3%-20.4%). The median time to progression was 14.9 weeks and median survival 19.9 weeks. Topotecan at this dose and schedule showed no substantial activity in relapsed gliomas.

Physical, psychological and social well-being of women with breast cancer: the influence of disease phase.

While research exists on the well-being of women during a specific phase of breast cancer, little research exists in which researchers utilized the same instruments to examine differences in women's well-being, based on the phase of their breast cancer. Using a trajectory framework, the purpose of this study is to examine the differences in the physical and social well-being of women during the following breast cancer states: newly diagnosed, adjuvant therapy, stable disease and recurrent disease. The convenience sample consisted of 35 women newly diagnosed with breast cancer, 52 women with breast cancer undergoing adjuvant therapy, 84 women whose breast cancer was considered stable and 64 women with recurrent breast cancer. Participants completed a packet of questionnaires which contained a demographic questionnaire, Short Form-36 (SF-36) Health Survey, a researcher designed (RD) questionnaire, Cancer Rehabilitation Evaluation System-Short Form (CARES-SF) and the Brief Symptom Inventory (BSI). Descriptive statistics, analysis of variance, and general linear F-tests were used to analyze the data. Differences were found across phases of disease on various subscales, including those representing perceived health states, overall impact, medical interactions, physical function, role function, fatigue, pain, social function and satisfaction with health. No significant differences were found between groups on the BSI subscales with the exception of somatization, global psychosocial measures, sexual and marital relation subscales. While individuals with recurrent disease often experienced more difficulties with their well-being than women in the other groups, women newly diagnosed and in the adjuvant group experienced more difficulties in select areas of well-being when compared with women in the stable group. Health care professionals need to recognize differences between groups to better meet the needs of patients with a breast cancer diagnosis.

Evaluation of soy phytoestrogens for the treatment of hot flashes in breast cancer survivors: A North Central Cancer Treatment Group Trial.

PURPOSE: Hot flashes represent a significant clinical problem for some breast cancer survivors. Safe, effective treatment is needed for this prominent clinical problem. Although it has been shown that estrogen or progesterone replacement therapy can alleviate this problem, there are continued safety concerns regarding the use of hormonal therapies in these women. Based on anecdotal information, we hypothesized that soy-derived phytoestrogens, weak estrogen-like substances in the soybean that demonstrate estrogen agonist and/or antagonist effects when they bind to estrogen receptors, could alleviate hot flashes. This current trial was designed to investigate this hypothesis. PATIENTS AND METHODS: This double-blind clinical trial involved breast cancer survivors with substantial hot flashes. After randomization, patients underwent a 1-week baseline period with no therapy. This was followed by 4 weeks of either soy tablets or placebo. The patients then crossed over to the opposite arm in a double-blind manner for the last 4 weeks. Patients completed a daily questionnaire documenting hot flash frequency, intensity, and perceived side effects. RESULTS: Of the 177 women who were randomized and started the study substance, 155 (88%) provided useable data over the first 5 weeks; 149 provided usable data over the entire 9 weeks. There was no suggestion that the soy product was more effective in reducing hot flashes than the placebo. At study completion, patients preferred the soy product 33% of the time, the placebo 37% of the time, and neither substance 31% of the time. No toxicity was observed. CONCLUSION: The soy product did not alleviate hot flashes in breast cancer survivors.

Sucralfate in the prevention of treatment-induced diarrhea in patients receiving pelvic radiation therapy: A North Central Cancer Treatment Group phase III double-blind placebo-controlled trial.

PURPOSE: Randomized studies have suggested that sucralfate is effective in mitigating diarrhea during pelvic radiation therapy (RT). This North Central Cancer Treatment Group study was undertaken to confirm the antidiarrheal effect of sucralfate. Several other measures of bowel function were also assessed. PATIENTS AND METHODS: Patients receiving pelvic RT to a minimum of 45 Gy at 1.7 to 2.1 Gy/d were eligible for the study. Patients were assigned randomly, in double-blind fashion, to receive sucralfate (1.5 g orally every 6 hours) or an identical looking placebo during pelvic RT. RESULTS: One hundred twenty-three patients were randomly assigned and found assessable. Overall, there was no significant difference in patient characteristics between those receiving sucralfate and those receiving placebo. Moderate or worse diarrhea was observed in 53% of patients receiving sucralfate versus 41% of those receiving placebo. Compared with patients receiving placebo, more sucralfate-treated patients reported fecal incontinence (16% v 34%, respectively; P =. 04) and need for protective clothing (8% v 23%, respectively; P =. 04). The incidence and severity of nausea were worse among those taking sucralfate (P =.03). Analysis of patient-reported symptoms 10 to 12 months after RT showed a nonsignificant trend toward more problems in patients taking sucralfate than in those taking placebo (average, 2.3 v 1.9 problems, respectively; P =.34). CONCLUSION: Sucralfate did not decrease pelvic RT-related bowel toxicity by any of the end points measured and seems to have aggravated some gastrointestinal symptoms.

Sex differences in fluorouracil-induced stomatitis.

PURPOSE: A meta-analysis of six North Central Cancer Treatment Group (NCCTG) trials involving patients receiving their first ever fluorouracil (5-FU)-based chemotherapy was undertaken to explore the association of sex with reports of the incidence and severity of stomatitis. PATIENTS AND METHODS: Data were obtained on a total of 731 patients (402 men and 329 women). Comparisons of incidence and severity rates and average stomatitis across sex were performed using standard binomial testing and t tests, respectively. Logistic regression analysis and a weighted analysis using data summarized to study level served as evidence of cross-validation. RESULTS: Women reported stomatitis both more often and with greater severity than did men. The incidence of any stomatitis for women was 63% versus 52% for men (P =.002). The incidence of severe or very severe stomatitis for men and women was 22% and 12%, respectively (P =. 0006). On average, women reported stomatitis of roughly 0.4 points higher than men on a 0 to 4 ordinal scale (P <.00001). Comparison of results across treatment and placebo arms was carried out to validate the initial findings. Logistic regression modelling further confirmed the results conditional on the presence of a number of potentially confounding covariates. Women were also 11% more likely than men to experience leukopenia of common toxicity criteria grade >/= 1, (70% v 59%, respectively; P <.00001) and grade 3+ (18% v 11%, respectively; P =.004). CONCLUSION: More women than men reported 5-FU-induced stomatitis. The precise mechanism resulting in different degrees of stomatitis across sex is not evident.

Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial.

BACKGROUND: Hot flashes can be troublesome, especially when hormonal therapy is contraindicated. Preliminary data have suggested that newer antidepressants, such as venlafaxine, can diminish hot flashes. We undertook a double-blind, placebo-controlled, randomised trial to assess the efficacy of venlafaxine in women with a history of breast cancer or reluctance to take hormonal treatment because of fear of breast cancer. METHODS: Participants were assigned placebo (n=56) or venlafaxine 37.5 mg daily (n=56), 75 mg daily (n=55), or 150 mg daily (n=54). After a baseline assessment week, patients took the study medication for 4 weeks. All venlafaxine treatment started at 37.5 mg daily and gradually increased in the 75 mg and 150 mg groups. Patients completed daily hot-flash questionnaire diaries. The primary endpoint was average daily hot-flash activity (number of flashes and a score combining number and severity). Analyses were based on the women who provided data throughout the baseline and study weeks. FINDINGS: 191 patients had evaluable data for the whole study period (50 placebo, 49 venlafaxine 37.5 mg, 43 venlafaxine 75 mg, 49 venlafaxine 150 mg). After week 4 of treatment, median hot flash scores were reduced from baseline by 27% (95% CI 11-34), 37% (26-54), 61% (50-68), and 61% (48-75) in the four groups. Frequencies of some side-effects (mouth dryness, decreased appetite, nausea, and constipation) were significantly higher in the venlafaxine 75 mg and 150 mg groups than in the placebo group. INTERPRETATION: Venlafaxine is an effective non-hormonal treatment for hot flashes, though the efficacy must be balanced against the drug's side-effects. Confirmation of the results of this 4-week study awaits the completion of three ongoing randomised studies to assess the effects of other related antidepressants for the treatment of hot flashes.

A randomized phase II and pharmacokinetic study of dacarbazine in patients with recurrent glioma.

We conducted a randomized phase II study to determine the efficacy of dacarbazine (DTIC) in recurrent gliomas. Patients were randomly assigned to receive either DTIC 750 mg/m2 IV day 1 every 28 days (Arm A) or DTIC 200 mg/m2 IV days 1-5 every 28 days (Arm B). Pharmacokinetics were studied in 6 patients on each arm using HPLC analysis. Thirty-nine patients (30 male, 9 female), ages 27-67 years (median 53) were entered on the study (20 on Arm A, 19 on Arm B). No objective responses were seen. Median time to progression was 3 months. Median survival was 8 months. Treatment was generally well tolerated. Major toxicities were grade 1-2 nausea (33%). lethargy (28%), diarrhea (15%), alopecia (15%), and grade 3 neutropenia (8%). Four patients on Arm A had mild self-limited episodes of intravascular hemolysis occurring immediately after drug infusion, the mechanism of which is unknown. Mean AUC for DTIC, HMMTIC (5-[3-hydroxymethyl-3-methyl-1-triazeno] imidazole-4-carboxamide), and MTIC (5-[3-methyl-1-triazenol imidazole-4-carboxamide), in Arm A were 14.8, 0.17, and 1.15 mM min, respectively. Corresponding values for Arm B (on day 1 of 5) were 1.7, 0.06, and 0.29 mM min, respectively. The predicted HMMTIC and MTIC exposure over 5 days for Arm B, based on the day 1 data, is higher than with Arm A. We conclude that DTIC is well tolerated but does not have activity in patients with recurrent gliomas. The 5-day schedule appears less toxic, and pharmacokinetic studies show that it provides greater exposure to MTIC and HMMTIC compared to the one-day schedule.

Tamoxifen-induced hot flashes.

Hot flashes are the most prominent side effect of tamoxifen, the most frequently prescribed antitumor agent in the world. Little detailed information is available to predict who will develop hot flashes on tamoxifen, to describe the natural history of these hot flashes, and/or to predict who will request therapy for such a side effect. This current trial was developed to address these items. Women who were about to begin adjuvant tamoxifen for locally treated breast cancer were approached for this trial. Before initiating tamoxifen, patients completed a short questionnaire designed to inquire about potential prognostic factors. Upon starting tamoxifen, women were asked to complete a hot flash diary daily for 3 months, and then daily for 1 week of each of the subsequent 9 months. Fifty patients, aged 51-83 years, provided data for this report. Approximately half of the women reported that they did not have any substantial hot flashes while the other half reported hot flashes of variable intensity. On average, these hot flashes gradually increased over 3 months and then plateaued. Baseline factors that appeared to predict for subsequent hot flash problems included a prior history of moderate to severe hot flashes with menopause and a history of prior estrogen therapy use. Overall, 16% of the women reported the desire for therapy for their hot flashes. Thirty-seven and one-half percent of the women (6/16) had a history of both prior estrogen use and moderate to severe hot flashes with menopause as compared to none (0/14) of the women without either of these factors. The data from this study can be utilized to better identify and educate women as to their probability of developing hot flashes after starting tamoxifen, to describe the average time frame for these hot flashes, and to predict the likelihood of whether resultant hot flashes will be substantial enough to have a woman request therapy for them.