Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 53-year-old man with metastatic bladder cancer was treated with multiple chemotherapy regimens with clear disease progression. At presentation in our clinics, he was symptomatic with severe pain, weight loss, fatigue, pain, and lower extremity edema. Hospice care had been recommended; however, the patient wanted to continue treatment. The patient was started on a novel bladder chemotherapy regimen using a combination of mitoxantrone and paclitaxel. This regimen has been shown to be effective in platinum refractory ovarian cancer but there are no prior data in bladder cancer. The patient's bladder cancer responded dramatically from a clinical, biochemical, and radiographic perspective.
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PMID:Substantial activity of mitoxantrone and paclitaxel in a heavily pre-treated metastatic bladder cancer patient. 1866 4

Advanced ovarian carcinoma in early progression (<6 months) (AOCEP) is considered resistant to most cytotoxic drugs. Gemcitabine (GE) and oxaliplatin (OXA) have shown single-agent activity in relapsed ovarian cancer. Their combination was tested in patients with AOCEP in phase II study. Fifty patients pre-treated with platinum-taxane received q3w administration of OXA (100 mg m(-2), d1) and GE (1000 mg m(-2), d1, d8, 100-min infusion). Patient characteristics were a : median age 64 years (range 46-79),and 1 (84%) or 2 (16%) earlier lines of treatment. Haematological toxicity included grade 3-4 neutropaenia (33%), anaemia (8%), and thrombocytopaenia (19%). Febrile neutropaenia occurred in 3%. Non-haematological toxicity included grade 2-3 nausea or vomiting (34%), grade 3 fatigue (25%),and grade 2 alopecia (24%). Eighteen (37%) patients experienced response. Median progression-free (PF) and overall survivals (OS) were 4.6 and 11.4 months, respectively. The OXA-GE combination has high activity and acceptable toxicity in AOCEP patients. A comparison of the doublet OXA-GE with single-agent treatment is warranted.
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PMID:Gemcitabine-oxaliplatin combination for ovarian cancer resistant to taxane-platinum treatment: a phase II study from the GINECO group. 1919 Jun 32

The purpose of this article is to describe interventions that may be used with women diagnosed with gynecological cancer who have radiation therapy and subsequently experience sexual difficulties. A PubMed search of articles containing specific key words (sexuality, sexual functioning, gynecological cancer, ovarian cancer, cervical cancer, vulval cancer, radiation therapy) was conducted. Articles were reviewed for applicability to the topic of interventions for sexual difficulties related to radiation therapy. A limited number of articles were found on the topic. Very little attention has been paid to the sexual difficulties women experience after radiation to the sexual organs. There are a limited number of interventions for the woman who has been treated for gynecological cancer with radiation. These focus on the provision of information and some specific suggestions related to treating vaginal dryness, the need for vaginal dilatation after radiation therapy, and management of fatigue. Gynecological cancer and its treatments can have a profound effect on sexual functioning in all phases of the sexual response cycle and on body image and sexual self-concept. A diagnosis of cancer and the associated distress may have a profound effect on the emotional status of both the woman and her partner. This psychological impact combined with the physical sensations of the disease itself and treatment side effects may lower both interest in sex and frequency of sexual activity.
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PMID:Interventions for sexuality after pelvic radiation therapy and gynecological cancer. 1919 73

There is increasing evidence of the efficacy of dose-dense therapy in the management of platinum-resistant/refractory ovarian cancer. We report our experience of extended weekly carboplatin and paclitaxel in this population group. Twenty patients with platinum-resistant/refractory ovarian cancer received carboplatin AUC 3 and paclitaxel 70 mg m(-2) on day 1, 8, 15 q 4 weekly for six planned cycles. Toxicity was assessed using Common Toxicity Criteria. Response was evaluated using radiological and CA125 criteria. Median age was 61 years (range 40-74 years). Median number of prior therapies is three (range 1-8). Response rate was 60% by radiological criteria (RECIST) and 76% by CA125 assessment. Grade 3 toxicities consisted of neutropenia (29% of patients) and anaemia (5%). One patient experienced grade 4 neutropenia. No grade 3/4 thombocytopaenia was reported. Fatigue, nausea and peripheral neuropathy were the most frequent non-hematological side effects. Median progression-free survival was 7.9 months and overall survival was 13.3 months. The dynamics of response to dose-dense therapy were as rapid as with front-line therapy within the same patient. This dose-dense regimen can be extended to at least 18 weekly cycles over 6 months and is well tolerated with high response rates in heavily pre-treated, platinum-resistant ovarian cancer. It forms a highly active and tolerable cytotoxic scaffold to which molecular-targeted therapies can be added in platinum-resistant ovarian cancer.
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PMID:Extended weekly dose-dense paclitaxel/carboplatin is feasible and active in heavily pre-treated platinum-resistant recurrent ovarian cancer. 1922 98

Despite progress in primary treatment of patients with advanced ovarian cancer, the majority develop recurrence of the disease. A platinum salt treatment, either as monotherapy or in combination with another cytostatic agent, is indicated for patients who have relapsed 6 or more months after primary treatment and thus have platinum-sensitive relapse. Because repeated use of paclitaxel treatment may lead to substantial neurotoxicity, the combination of gemcitabine with carboplatin represents a suitable treatment option, which is widely used in common clinical practice in the Czech Republic and Slovakia. This non-interventional, prospective study observed the effectiveness and tolerability of second-line treatment with gemcitabine and carboplatin in patients with platinum-sensitive relapse of ovarian cancer in routine clinical practice. The primary endpoint was to evaluate the survival and secondary endpoints were to evaluate time to disease progression, objective tumor response rate, and treatment toxicity. Patients were enrolled to planned second-line treatment with gemcitabine and carboplatin (gemcitabine 1000 mg/m2 and carboplatin AUC 5 on Day 1, and gemcitabine 1000 mg/m2 on Day 8 of a 21-day cycle) for platinum-sensitive relapse of ovarian cancer as a part of routine clinical practice and followed for 12 months. The events (death, tumor progression), tumor response, and maximal grades of toxicity were recorded according to common clinical practice. Survival time (using Kaplan-Meier analysis) and objective tumor response rate were calculated using data forms, and a subgroup analysis was performed using log rank tests for time-to-event endpoints; p-values were also calculated. Response rates were calculated for the whole population; for the subgroups, the Fisher's exact test was performed and only p-values were calculated. Between January 2004 and June 2005, 53 patients were enrolled in the study. The median age was 57 years and 96% of patients had an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of 0 and 1 at baseline. Approximately 91% of patients were originally diagnosed with stage III or IV; 60% of patients had disease free intervals (DFIs) of 12 or more months from previous therapy, and the additional 40% less than 12 months. The 1-year survival rate was 83%. Median survival time was not determined within the 12-month period following the start of the treatment study due to the limited duration of follow-up. Objective tumour response rate was 67.3%. Most common reasons for discontinuation of therapy were "Planned treatment completed" (53%) and "Tumor progression" (11%). Most common toxicities were leukopenia, anaemia, neutropenia, and thrombocytopenia; grades 3 and 4 of these toxicity types did not exceed 30%. Febrile neutropenia was recorded in two patients. Most common non-haematological toxicities were nausea and vomiting, fatigue, and neuropathy; grades 3 and 4 of these were below 6%. Results on time to disease progression are not published due to inconsistent statistical analysis of reported data. Based on this observation from routine clinical practice, which corresponds with previously published results from controlled clinical trials, the gemcitabine and carboplatin combination seems to be a suitable therapeutic option for patients with platinum-sensitive relapse of ovarian cancer.
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PMID:Gemcitabine and carboplatin treatment in patients with relapsing ovarian cancer. 1947 54

PURPOSE Studies on quality of life (QOL) among women with endometrial cancer have shown that patients who undergo pelvic radiotherapy report lower role functioning and more diarrhea and fatigue. In the Post Operative Radiation Therapy in Endometrial Cancer (PORTEC) trial, patients with endometrial carcinoma were randomly assigned to receive external-beam radiotherapy (EBRT) or vaginal brachytherapy (VBT). QOL was evaluated by using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and subscales from the prostate cancer module, PR-25, and the ovarian cancer module, OV-28. PATIENTS AND METHODS PORTEC-2 accrued 427 patients between 2002 and 2006, of whom 214 were randomly assigned to EBRT, and 213 were randomly assigned to VBT. Three-hundred forty-eight patients (81%) were evaluable for QOL. QOL outcomes were analyzed at a median follow-up of 2 years. Results At baseline after surgery, patient functioning was at the lowest level, and it increased during and after radiotherapy to reach a plateau after 12 months. Patients in the VBT group reported better social functioning (P < .002) and lower symptom scores for diarrhea, fecal leakage, the need to stay close to the toilet, and limitation in daily activities because of bowel symptoms (P < .001). At baseline, 15% of patients were sexually active; this increased significantly to 39% during the first year (P < .001). Sexual functioning and symptoms did not differ between the treatment groups. CONCLUSION Patients who received EBRT reported significantly higher levels of diarrhea and bowel symptoms. This resulted in a higher need to remain close to a toilet and, as a consequence, more limitation of daily activities because of bowel symptoms and decreased social functioning. Vaginal brachytherapy provides a better QOL, and should be the preferred treatment from a QOL perspective.
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PMID:Quality of life after pelvic radiotherapy or vaginal brachytherapy for endometrial cancer: first results of the randomized PORTEC-2 trial. 1954 4

PURPOSE AMG 386 is an investigational peptide-Fc fusion protein (ie, peptibody) that inhibits angiogenesis by preventing the interaction of angiopoietin-1 and angiopoietin-2 with their receptor, Tie2. This first-in-human study evaluated the safety, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of AMG 386 in adults with advanced solid tumors. PATIENTS AND METHODS Patients in sequential cohorts received weekly intravenous AMG 386 doses of 0.3, 1, 3, 10, or 30 mg/kg. Results Thirty-two patients were enrolled on the study and received AMG 386. One occurrence of dose-limiting toxicity was seen at 30 mg/kg: respiratory arrest, which likely was caused by tumor burden that was possibly related to AMG 386. The most common toxicities were fatigue and peripheral edema. Proteinuria (n = 11) was observed without clinical sequelae. Only four patients (12%) experienced treatment-related toxicities greater than grade 1. A maximum-tolerated dose was not reached. PK was dose-linear and the mean terminal-phase elimination half-life values ranged from 3.1 to 6.3 days. Serum AMG 386 levels appeared to reach steady-state after four weekly doses, and there was minimal accumulation. No anti-AMG 386 neutralizing antibodies were detected. Reductions in volume transfer constant (K(trans); measured by dynamic contrast-enhanced magnetic resonance imaging) were observed in 10 patients (13 lesions) 48 hours to 8 weeks after treatment. One patient with refractory ovarian cancer achieved a confirmed partial response (ie, 32.5% reduction by Response Evaluation Criteria in Solid Tumors) and withdrew from the study with a partial response after 156 weeks of treatment; four patients experienced stable disease for at least 16 weeks. CONCLUSION Weekly AMG 386 appeared well tolerated, and its safety profile appeared distinct from that of vascular endothelial growth factor-axis inhibitors. AMG 386 also appeared to impact tumor vascularity and showed antitumor activity in this patient population.
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PMID:Safety, pharmacokinetics, and antitumor activity of AMG 386, a selective angiopoietin inhibitor, in adult patients with advanced solid tumors. 1954 6

Development of the pros and cons of intraperitoneal (IP) chemotherapy in the treatment of epithelial ovarian cancer based on the most prominent data published on the evolution of IP chemotherapy and on experience with this therapeutic strategy in clinical routine. The literature published on IP chemotherapy in ovarian cancer between 1970 and 2008 was identified systematically by computer-based searches in MEDLINE and the Cochrane Library. Furthermore, a preliminary analysis of data recorded during an observational nationwide multicenter study of the Austrian AGO on IP-IV chemotherapy using the GOG-172 treatment regimen was performed. The literature review unequivocally revealed a significantly greater toxicity for IP than for intravenous (IV) cisplatin-based chemotherapy. However, according to a Cochrane meta-analysis, IP-IV administration of chemotherapy is associated with a 21.6% decrease in the risk for death. In agreement with earlier reports, the most frequently mentioned side-effects in the Austria-wide observational study were long-lasting neurotoxicity, abdominal pain, fatigue, gastrointestinal and metabolic toxicities, and catheter-related complications. Most of these toxicities were identified as mirroring the toxicity profile of high-dose IV cisplatin (>or=100 mg/m(2)). In some patients, the classic IP-IV regimen with cisplatin/paclitaxel was changed to an alternative schedule comprising carboplatin AUC 5 (d1) and weekly paclitaxel 60 mg/m(2) (d1, 8, 15) completely administered via the IP route. This treatment was better tolerated and quality of life was significantly less compromised. However, neutropenia and thrombocytopenia were the limiting side-effects of this IP regimen. In cases where optimal cytoreduction with residual disease <or=1 cm was achieved during primary surgery and disease was confined to the peritoneal cavity, IP chemotherapy should be given serious consideration, even at the expense of significantly increased, but manageable toxicity.
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PMID:Pros and cons of intraperitoneal chemotherapy in the treatment of epithelial ovarian cancer. 1959 65

Epithelial ovarian cancer is the fourth biggest cause of cancer-related death in women. Over recent decades, improvements have been made in treatment outcome in terms of response rate and survival. To date, intensive surgical staging and cytoreduction, followed by primary chemotherapy with the carboplatin-paclitaxel regimen, are considered the gold standard for the management of this disease. Nevertheless, despite good initial response to systemic therapy after optimal debulking surgery, the long-term survival remains poor, with a high risk of recurrence. Furthermore, medical therapy of ovarian cancer impacts quality of life owing to the common occurrence of chemotherapy side effects, such as alopecia, neurotoxicity and fatigue. In order to improve the efficacy and reduce the toxicity of first-line chemotherapy, more than 10,000 women have been involved in worldwide randomized trials in the last 10 years. Several treatment alternatives have been investigated, such as intraperitoneal chemotherapy, alternative doublets and triplet regimens, in the effort to find an optimal first-line treatment strategy. In this review we discuss the results of these trials, the recent progresses and the most important ongoing studies, including those with emerging target and biological agents.
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PMID:First-line treatment of advanced ovarian cancer: current research and perspectives. 2001 85

This study investigated the association between positive genetic diagnosis for BRCA1/2 mutations and sleep quality in Ashkenazi asymptomatic women. Seventy-three women, including 17 asymptomatic BRCA1/2 carriers and 20 non-carriers from the oncogenetic clinic, and 36 community controls, participated in a cross-sectional design. Women completed sociodemographic, clinical, general psychological distress, cancer-related worry (CRW), fatigue and sleep questionnaires in their homes, and wore actigraphs for 5-7 nights. Impaired global subjective sleep quality was demonstrated in BRCA1/2 carriers compared to non-carriers and controls [mean Pittsburgh sleep quality index (PSQI) total scores 7.29 +/- 4.34; 3.94 +/- 2.49; 4.21 +/- 2.80, respectively, P = 0.021] and poor sleep quality (PSQI total score >5) was significantly higher in carriers (53%) compared to non-carriers (20%) and controls (28%, P = 0.03). Based on actigraphic measures, sleep latency tended to be longer in carriers compared to counterparts, albeit not significantly. Increased sleep disturbance was related significantly to increased fatigue in the entire sample and in the control group; to psychological distress in the entire sample and in non-carriers; and to CRW in the entire sample. In carriers, sleep disturbance was related strongly but non-significantly to fatigue, psychological distress and CRW. Fatigue and carrier status were significant predictors of sleep quality, accounting for 15.7% of the variance. In conclusion, asymptomatic BRCA1/2 carriers experience poor sleep quality compared to non-carriers and controls. Our study design is unique in that it offers insight regarding the nature of being an asymptomatic carrier, and affords the opportunity to examine factors that may contribute to the development of insomnia in women at risk for breast-ovarian cancer.
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PMID:Sleep disturbances in asymptomatic BRCA1/2 mutation carriers: women at high risk for breast-ovarian cancer. 2033 6


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