[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.

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.

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.

[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.

[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.

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.

Do American oncologists know how to use prognostic variables for patients with newly diagnosed primary breast cancer?

PURPOSE: This project was designed to investigate how American medical oncologists actually use prognostic information to treat primary breast cancer patients, and to study their difficulties in combining complex and sometimes contradictory information. METHODS: A simple 2-page questionnaire was faxed in May and June 1993 to a sample of American medical oncologists who were members of the American Society of Clinical Oncology (ASCO). RESULTS: When presented with simple case histories of patients with newly diagnosed invasive breast cancer and asked to assess prognosis on the basis of tumor size, number of involved axillary nodes, patient age, estrogen receptor level, and progesterone receptor level, there was a wide divergence of opinions about the probability of disease-free survival at 10 years (both for cases in which the patient received no adjuvant therapy and for those in which the patient did receive such therapy). The use of additional prognostic data (such as S-phase, tumor histologic and nuclear grading, and cathepsin D status) did not refine the estimates, but led to an equal or greater dispersion of estimates of prognosis. CONCLUSION: There is a clear need for tools to help oncologists integrate prognostic information for primary breast cancer patients. Such tools might lead to greater accuracy and uniformity of prognostic estimates. Such tools might also help make clear what prognostic tests are worth using for routine clinical practice.

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.

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.

Regular use of a verbal pain scale improves the understanding of oncology inpatient pain intensity.

PURPOSE: This study was undertaken to determine if the daily use of a verbal pain scale could improve the correlation of pain perception between hospitalized oncology patients and their caregivers. PATIENTS AND METHODS: Hospitalized oncology patients were asked to rate verbally their average pain over the past 24 hours on a scale ranging from 0 to 10. The patients' primary-care physicians and nurses were asked the same question on the same morning after they had evaluated their patients. RESULTS: During a baseline study, only 64% of caregivers' pain scores were within two points of the respective patient's score. Caregivers tended to underestimate patients' pain scores. Caregivers were alerted to these poor results and then requested to ask each patient daily for the average pain score and record this score on the patient's medical record. Nonetheless, correlation between patients' and caregivers' pain scores remained poor (68% within two points of each other) during a second study. The major reason for the poor results appeared to be because caregivers did not routinely ask patients for pain scores. Subsequently, a renewed, more intensive educational effort was undertaken and a third study was conducted. During the third study, 85% of caregivers' and patients' pain scores were within two points of each other (P = .001 when compared with baseline). CONCLUSION: The enforced use of a simple verbal pain assessment tool appears to improve caregiver's understanding of the pain status of hospitalized oncology patients.

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.

Prospective evaluation of prognostic variables from patient-completed questionnaires. North Central Cancer Treatment Group.

PURPOSE: This study was developed to determine whether descriptive information from a patient-completed questionnaire could provide prognostic information that was independent from that already obtained by the patient's physician. PATIENTS AND METHODS: An initial detailed questionnaire was administered to approximately 150 patients with advanced cancer. This questionnaire was subsequently revised and given to a total of 1,115 patients with advanced colorectal or lung cancer. Univariate and multivariate analyses were performed to evaluate the data from these questionnaires. RESULTS: A total of 36 variables showed statistically significant prognostic information for survival in univariate analyses, even though many of these variables were associated with only a minimal increase in risk. A multivariate analysis demonstrated that there was a high correlation between many variables. Three major groups of variables became apparent as providing strong prognostic information. These included the following: (1) a physician's assessment of performance status (PS); (2) a patient's assessment of their own PS; and (3) a nutritional factor such as appetite, caloric intake, or overall food intake. CONCLUSION: Data generated by a patient-completed questionnaire can provide important prognostic information independent from that obtained by other physician-determined prognostic factors.

Randomized trial of a chlorhexidine mouthwash for alleviation of radiation-induced mucositis.

PURPOSE: To determine whether a chlorhexidine mouthwash could alleviate radiation-induced oral mucositis. PATIENTS AND METHODS: Patients scheduled to receive radiation therapy to include greater than one third of the oral cavity mucosa were selected for study. Following stratification, they were randomized in a double-blind manner to receive a chlorhexidine mouthwash or a placebo mouthwash. Both groups were then similarly evaluated for mucositis and mouthwash toxicity. RESULTS: Twenty-five patients were randomized to receive the chlorhexidine mouthwash, while 27 received the placebo mouthwash. Treatment arms were well balanced. There was a trend for more mucositis and there was substantially more toxicity (eg, mouthwash-induced discomfort, taste alteration, and teeth staining) on the chlorhexidine arm. CONCLUSION: In contrast to the prestudy hypothesis that a chlorhexidine mouthwash might provide benefit for patients receiving radiation therapy to the oral mucosa, this study provides strong evidence suggesting that a chlorhexidine mouthwash is detrimental in this clinical situation.

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.

Prospective evaluation of vitamin E for hot flashes in breast cancer survivors.

PURPOSE: Hot flashes represent a substantial clinical problem for some breast cancer survivors. Although estrogen or progesterone preparations can alleviate these symptoms in many patients, concern remains regarding the use of hormonal preparations in such women. Thus, there is a perceived need for nonhormonal treatments for hot flashes for breast cancer survivors. Based on anecdotal evidence that vitamin E was helpful, we designed a trial to investigate this matter. METHODS: We developed and conducted a placebo-controlled, randomized, crossover trial where, after a 1 week baseline period, patients received 4 weeks of vitamin E 800 IU daily, then 4 weeks of an identical-appearing placebo, or vice versa. Diaries were used to measure potential toxicities and hot flashes during the baseline week and the two subsequent 4-week treatment periods. RESULTS: The 120 patients evaluated for toxicity failed to show any. The 105 patients who finished the first treatment period showed a similar reduction in hot flash frequencies (25% v 22%; P = .90) for the two study arms. A crossover analysis, however, showed that vitamin E was associated with a minimal decrease in hot flashes (one less hot flash per day than was seen with a placebo) (P < or = .05). At the study end, patients did not prefer vitamin E over the placebo (32% v 29%, respectively). CONCLUSION: Although this trial was able to show a statistically significant hot flash reduction with vitamin E compared to a placebo, the clinical magnitude of this reduction was marginal.

Phase III controlled evaluation of sucralfate to alleviate stomatitis in patients receiving fluorouracil-based chemotherapy.

PURPOSE: Stomatitis is a major dose-limiting toxicity of bolus fluorouracil (5FU)-based chemotherapy regimens, despite the use of oral cryotherapy. Pursuant to preliminary data that suggested a sucralfate oral solution could alleviate chemotherapy-induced oral mucositis, we developed a prospective trial to test this contention. PATIENTS AND METHODS: A phase III, double-blind, placebo-controlled clinical trial was designed. Patients were entered onto the study at the time of the first cycle of 5FU-based chemotherapy. All patients received oral cryotherapy for 30 minutes with each dose of 5FU. In addition, each patient was randomized to receive either a sucralfate solution or a placebo solution to be used if they developed mouth tenderness or mouth sores. The study solution was to be used four times daily for 7 days starting on the first day of mouth tenderness or mouth sores. Stomatitis scores were determined by health care providers and by patients themselves. RESULTS: There was a total of 131 assessable patients entered onto this trial, 50 of whom developed mucositis and used the study medication (27 sucralfate and 23 placebo). There was no suggestion of any difference in stomatitis severity or duration on either protocol arm. CONCLUSION: The resultant data from this clinical trial did not support the prestudy hypothesis that sucralfate would be beneficial for the treatment of 5FU-induced stomatitis.

Pilot evaluation of venlafaxine hydrochloride for the therapy of hot flashes in cancer survivors.

PURPOSE: Hot flashes can be a prominent clinical problem for breast cancer survivors and men who undergo androgen-deprivation therapy. Anecdotal information suggested a low dose of a relatively new antidepressant, venlafaxine, could abrogate this clinical problem. MATERIALS AND METHODS: This study included 28 consecutive assessable patients entered onto a phase II clinical trial. Hot flash data were collected by daily diary questionnaires during a 1-week baseline period and then for 4 weeks, during which time patients received venlafaxine 12.5 mg orally twice daily. RESULTS: Fifty-eight percent of patients who completed the study had a greater than 50% reduction in hot flash scores (frequency times severity) during the fourth treatment week as compared with the baseline week. Median weekly hot flash scores were reduced by 55% from baseline during the fourth week of venlafaxine therapy. Therapy was generally well tolerated and appeared to alleviate fatigue, sweating, and trouble sleeping. CONCLUSION: Venlafoxine appears to represent an efficacious new method to alleviate hot flashes. Further evaluation of this compound for alleviating hot flashes is indicated.

Phase II trial of nitrogen mustard, vincristine, and procarbazine in patients with recurrent glioma: North Central Cancer Treatment Group results.

PURPOSE: Previous investigators have reported responses in 52% of patients treated with mechlorethamine (nitrogen mustard), vincristine, and procarbazine (MOP) for recurrent glioma. To confirm these promising results, we conducted a phase II prospective study. PATIENTS AND METHODS: Sixty-three patients with histologic confirmation of recurrent glioma were treated with the MOP regimen. Patients with or without prior chemotherapy received nitrogen mustard 3 mg/m2 or 6 mg/m2, respectively, intravenously on days 1 and 8 plus vincristine 2 mg/m2 intravenously on days 1 and 8, and procarbazine 100 mg/m2 orally on days 1 to 14. Cycles were repeated every 28 days. RESULTS: Of 61 patients assessable for response, eight responded (13%), with one complete response (CR). Responses were as follows: low-grade gliomas, 19%; anaplastic astrocytomas, 11%; anaplastic oligodendrogliomas or oligoastrocytomas, 25%; and glioblastomas, 4.3%. The most common toxicity was myelosuppression with leukocyte nadirs less than 1,000/microL in 23% and platelet nadirs less than 25,000/microL in 13% of patients. Two patients died of infection in the setting of neutropenia. Nonhematologic toxicity included neurosensory changes in 21% of patients (severe in 3%) and severe dermatologic reactions in 8%. In multivariate analysis, Eastern Cooperative Oncology group (ECOG) performance status (PS) was the best predictor for response to chemotherapy (P=.01) and time to progression (P=.008), while PS and grade were the most important predictors of survival (P=.002 and .05, respectively). CONCLUSION: This study did not confirm the high response rate previously reported in recurrent gliomas. Patients with recurrent anaplastic oligodendrogliomas or oligoastrocytomas and recurrent low-grade gliomas had the highest response rates (25% and 19%, respectively). In multivariate analysis, ECOG PS was the best predictor of response, while PS and tumor grade were the most important predictors of survival.

Randomized comparison of megestrol acetate versus dexamethasone versus fluoxymesterone for the treatment of cancer anorexia/cachexia.

PURPOSE: Previous double-blind, placebo-controlled, randomized clinical trials have demonstrated that both corticosteroids and progestational agents do partially alleviate cancer anorexia/cachexia. Pilot information suggested that an anabolic corticosteroid might also improve appetite in patients with cancer anorexia/cachexia. The current trial was developed to compare and contrast a progestational agent, a corticosteroid, and an anabolic corticosteroid for the treatment of cancer anorexia/cachexia. PATIENTS AND METHODS: Patients suffering from cancer anorexia/cachexia were randomized to receive either dexamethasone 0. 75 mg qid, megestrol acetate 800 mg orally every day, or fluoxymesterone 10 mg orally bid. Patients were observed at monthly intervals to evaluate weight changes and drug toxicity. Patients also completed questionnaires at baseline and at monthly intervals to evaluate appetite and drug toxicities. RESULTS: Fluoxymesterone resulted in significantly less appetite enhancement and did not have a favorable toxicity profile. Megestrol acetate and dexamethasone caused a similar degree of appetite enhancement and similar changes in nonfluid weight status, with nonsignificant trends favoring megestrol acetate for both of these parameters. Dexamethasone was observed to have more corticosteroid-type toxicity and a higher rate of drug discontinuation because of toxicity and/or patient refusal than megestrol acetate (36% v 25%; P =.03). Megestrol acetate had a higher rate of deep venous thrombosis than dexamethasone (5% v 1%; P =.06). CONCLUSION: Whereas fluoxymesterone clearly seems to be an inferior choice for treating cancer anorexia/cachexia, megestrol acetate and dexamethasone have similar appetite stimulating efficacy but differing toxicity profiles.