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)

We assessed the tolerability, safety, pharmacokinetics and dose-limiting toxicity (DLT) of the recombinant humanized IgG4 anti-vascular endothelial growth factor (VEGF) monoclonal antibody, HuMV833, in patients with advanced cancer. Cohorts of patients with progressive solid tumours received escalating doses of HuMV833 as a 1-h intravenous (I.V.) infusion on days 1, 15, 22, and 29. Twenty patients (median Eastern Cooperative Oncology Group (ECOG) score 1) were accrued. HuMV833 infusions were well tolerated and there were no grade III or IV toxicities definitely related to the antibody. Grade I or II toxicities probably related to the antibody included fatigue, dyspnoea and rash. There were two episodes of asymptomatic hypocalcaemia, one at grade III and one grade IV, which were recorded in early follow-up. There were eight grade I episodes of asymptomatic elevation of activated partial thromboplastin time (APTT) and two grade III events; one in a patient receiving 1 mg/kg and the other receiving extended doses of 10 mg/kg. Pharmacokinetic analysis revealed a non-linear kinetic and an elimination half-life of between 8.2 (0.3 mg/kg) and 18.7 (10 mg/kg) days. One patient with ovarian cancer experienced a partial response (PR) of 9 months duration and eight had disease stabilisation (SD) including one patient with colorectal carcinoma whose disease was stable for 14 months. In 13 of the 14 samples taken from 12 patients, the plasma concentration of hepatocyte growth factor (HGF) was reduced 24 h after drug administration. HuMV833 is safe and lacked DLT at doses up to 10 mg/kg on this schedule. Multiple doses were well tolerated, despite occasional asymptomatic elevations in APTT. By combining pharmacokinetic, pharmacodynamic and toxicity data, we can identify doses of 1 and 3mg/kg for further investigation. HuMV833 appears to possess some clinical activity.
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PMID:Phase I investigation of recombinant anti-human vascular endothelial growth factor antibody in patients with advanced cancer. 1573 60

We present a case of systemic sarcoidosis with ovarian and peritoneal involvement. The atypical clinical presentation of the disease has lead to a problem of the differential diagnosis with ovarian cancer. A 72-year-old female was admitted because of low grade fever, fatigue and dilatation of the abdomen. Clinical and laboratory evaluation of the patient revealed moderate right pleural effusion, ascites, diffuse ovarian infiltration, presence of enlarged intraabdominal lymph nodes and a substantially high value of serum CA 125. Histological examination after laparotomy was indicative of ovarian sarcoidosis.
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PMID:A case of ovarian sarcoidosis mimicking malignancy. 1585 40

In this issue of The Oncologist, Armstrong et al. present an analysis of the use of topotecan (Hycamtin; GlaxoSmithKline, Philadelphia, http://www.gsk.com) in the second-line treatment of both ovarian cancer and small cell carcinoma of the lung. This cytotoxic agent has clearly been demonstrated to be a useful drug in a population of patients with both of these conditions. However, the description of the nature of the toxicity, as stated in the manuscript, must be questioned along with comments made regarding the relative toxicity of alternative cytotoxic agents frequently used in similar settings. The purpose of this discussion absolutely is not to negate the unquestioned, demonstrated usefulness of topotecan as second-line therapy in ovarian cancer but rather to point out that the U.S. Food and Drug Administration-approved dose level of 1.5 mg/m(2) per day x 5 days can cause substantial and highly clinically relevant bone marrow toxicity. Whether this toxicity, which can result in a level of fatigue that may cause responding patients to discontinue treatment, should simply be labeled "excessive" rather than "cumulative" appears to be a matter of semantics rather than an important distinction. Whether delivery of a lower dose of topotecan (1 mg/m(2)-1.25 mg/m(2) per day x 5 days) will essentially eliminate concern for the development of severe clinically relevant marrow toxicity is uncertain, but the risk will certainly be substantially reduced.
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PMID:Topotecan as second-line therapy for ovarian cancer: dosage versus toxicity. 1624 49

We carried out a phase II nonrandomized study to examine the level of activity of oxaliplatin, pegylated liposomal doxorubicin, and cyclophosphamide in a patient population with relapsed ovarian cancer pretreated with platinum derivatives and paclitaxel. Patients received oxaliplatin (85 mg/m2), pegylated liposomal doxorubicin (30 mg/m2), and cyclophosphamide (750 mg/m2). A total of 49 patients (39 assessable for toxicity and response) were enrolled in this trial. Neutropenia grade 3 was observed in six patients (15%) and anemia grade 3 in one patient (0.2%). Fatigue grade 1-2 occurred in 26 patients (66%), nausea/vomiting grade 1 in 23 patients (58%), and alopecia grade 1-2 in 19 patients (48%). Twenty-one (53%) patients experienced grade 1-2 peripheral neuropathy. The overall response rate was 46% (95% CI 23.6-68.7). Median progression-free survival was 28 weeks (range 12-52 weeks) and median survival was 45 weeks (range 26-136+ weeks). The mean duration of response was 34 weeks (range 16-52 weeks). In platinum-resistant and -refractory ovarian cancer patients, the overall response rate was 37% (CI 95% 14.4-60.8) with a progression-free survival of 28 weeks (range 12-52 weeks) and a median survival of 42 weeks (range 28-84 weeks). This combination chemotherapy is generally well tolerated and is an active second-line regimen against ovarian cancer.
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PMID:A phase II study of pegylated liposomal doxorubicin oxaliplatin and cyclophosphamide as second-line treatment in relapsed ovarian carcinoma. 1651 72

This study's objectives were to determine the maximum tolerated dose (MTD) of 9-aminocamptothecin (9-AC), given as a prolonged continuous infusion (CI) for 7-21 days, when formulated in dimethylacetamide/polyethylene glycol 400 (DMA) and then later as a colloidal dispersion (CD), and to determine the steady-state pharmacokinetics of 9-AC. Patients with solid tumors refractory to standard therapy were enrolled on this study. Total dose/cycle of 9-AC/DMA was initially escalated by duration (7-21 days), while keeping the dose rate constant at 6.2 microg/m/h (1.04-3.12 mg/m/4-week cycle). Then, the dose rate was escalated from 6.2 to 21.1 microg/m/h (3.12-10.6 mg/m/4-week cycle) while keeping the infusion duration constant at 21 days. CD formulation was escalated from 14.1 to 25 microg/m/h (7.11-12.60 mg/m/4-week cycle) while keeping the infusion duration constant at 21 days and then escalated from 28.1 to 37.5 microg/m/h (9.44-12.60 mg/m/3-week cycle) while keeping the infusion duration constant at 14 days. Sixty-two patients were evaluable for toxicity; 61 received prior chemotherapy (median 3 regimens/patient). No consistent dose-limiting toxicity (DLT) was encountered with the DMA formulation until dose level 10.60 mg/m/cycle, when two patients experienced DLTs. With the 21-day CD formulation, the MTD was 12.60 mg/m/cycle with three DLTs out of five patients. When 9-AC was given on the 14-day schedule, DLT was seen at 9.44, 11.20 and 12.60 mg/m/cycle, with consistent DLT at the two highest dose levels. All DLTs for both formulations were grade 4 hematologic toxicities (neutropenia and/or thrombocytopenia), while non-hematologic toxicities were relatively mild (including gastrointestinal toxicities and fatigue). One patient with ovarian cancer had a complete response and three had partial responses (PRs). One patient each with non-Hodgkin's lymphoma and cancer of unknown primary had a PR. Pharmacokinetic studies of both formulations of 9-AC revealed a linear relationship between increasing plasma 9-AC lactone concentration and dose. The median plasma 9-AC lactone concentration for 9-AC/CD was approximately twice that achieved by 9-AC/DMA for the same dose level. Both 9-AC formulations, given as a 21-day CI, were well tolerated with dose-limiting myelosupression at the MTD. This dose intensity exceeds that of other 9-AC phase I/II schedules. The recommended phase II dose (RPTD) is 9.42 mg/m/4-week cycle, given as a 21-day infusion. The 14-day schedule of 9-AC/CD was equally myelosuppressive with the RPTD of 9.44 mg/m/3-week cycle, although two heavily pre-treated patients (one with pelvic radiotherapy) could not tolerate this dose. Objective responses were observed in six out of 57 heavily pre-treated patients, most of which had ovarian cancer.
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PMID:Phase I trial of continuous infusion 9-aminocamptothecin in patients with advanced solid tumors: 21-day infusion is an active well-tolerated regimen. 1670 15

This study used electronic diaries to examine patterns of mood and physical symptoms within and across days in two independent samples of cancer patients. Twenty-three breast cancer survivors (post-treatment) and 33 ovarian cancer survivors (on chemotherapy) recorded mood and physical symptoms 4 times daily for 7 consecutive days. A series of repeated-measures multilevel models using SAS Proc Mixed were calculated to estimate the degree to which physical symptoms (e.g., pain, fatigue, and nausea) were associated with participants' moods. Across days, mood vectors with a pleasantness component (i.e., happy-sad and calm-anxious) and mood vectors with an arousal component (i.e., active-passive and peppy-tired) were significantly associated with physical symptom severity. Specifically, breast cancer survivors with greater fatigue and pain reported more negative moods (eta2 < or = 0.33). Ovarian cancer survivors with greater fatigue (eta2 < or = 0.35), pain (eta2 < or = 0.04), and nausea (eta2 < or = 0.04) also reported more negative moods. Diurnal analyses showed that happy-sad (eta2 < or = 0.16), active-passive (eta2 < or = 0.27), and peppy-tired moods (eta2 < or = 0.33) were significantly negatively associated with fatigue at each of the four daily assessment times in both samples. Although correlational, our findings are consistent with previous studies suggesting that variations in both pleasant and aroused mood covary with changes in real-time physical symptom reports.
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PMID:Mood states associated with transitory physical symptoms among breast and ovarian cancer survivors. 1670 84

Subjective and objective evidence suggest that a third to half of patients developing ovarian cancer report symptoms at 3 or more months prior to diagnosis. Early ovarian cancer-associated symptoms constitute a constellation of mostly nongynecological complaints, suggesting a visceral disturbance, which do not point immediately to a pelvic origin. Abdominal bloating and pain predominate with recent onset and multiple symptomatic episodes. Gastrointestinal and urinary symptoms and fatigue/malaise may be part of the symptom complex. Women aged 50 years and older with this constellation of symptoms should have medical evaluation and, if symptoms are unexplained or persist, should undergo pelvic imaging (e.g., transvaginal ultrasound) and serum CA125.
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PMID:Early clinical detection of ovarian cancer: a review of the evidence. 1683 Oct 76

Seliciclib (CYC202; R-roscovitine) is the first selective, orally bioavailable inhibitor of cyclin-dependent kinases 1, 2, 7 and 9 to enter clinical trial. Preclinical studies showed antitumour activity in a broad range of human tumour xenografts. A phase I trial was performed with a 7-day b.i.d. p.o. schedule. Twenty-one patients (median age 62 years, range: 39-73 years) were treated with doses of 100, 200 and 800 b.i.d. Dose-limiting toxicities were seen at 800 mg b.i.d.; grade 3 fatigue, grade 3 skin rash, grade 3 hyponatraemia and grade 4 hypokalaemia. Other toxicities included reversible raised creatinine (grade 2), reversible grade 3 abnormal liver function and grade 2 emesis. An 800 mg portion was investigated further in 12 patients, three of whom had MAG3 renograms. One patient with a rapid increase in creatinine on day 3 had a reversible fall in renal perfusion, with full recovery by day 14, and no changes suggestive of renal tubular damage. Further dose escalation was precluded by hypokalaemia. Seliciclib reached peak plasma concentrations between 1 and 4 h and elimination half-life was 2-5 h. Inhibition of retinoblastoma protein phosphorylation was not demonstrated in peripheral blood mononuclear cells. No objective tumour responses were noted, but disease stabilisation was recorded in eight patients; this lasted for a total of six courses (18 weeks) in a patient with ovarian cancer.
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PMID:A phase I trial of the selective oral cyclin-dependent kinase inhibitor seliciclib (CYC202; R-Roscovitine), administered twice daily for 7 days every 21 days. 1717 92

A diagnosis of gynaecological cancer and its treatment are usually associated with many physical and psychological changes, both as a result of the diagnosis itself and of the usual treatments of surgery, radiotherapy and/or several months of chemotherapy. Patients often experience symptoms such as fatigue, abdominal swelling and pain, and suffer from emotional distress and disturbances of their life style. Sexual functioning can also be affected. Often there are physiological difficulties, such as vaginal dryness, together with psychological distress and relationship problems. This chapter discusses the ways in which gynaecological cancer can impact sexual functioning, and presents findings from a research project that was undertaken to begin to understand how sexual functioning can be affected by ovarian cancer. The article also makes recommendations for how health-care professionals can help women to cope better with psychosexual dysfunction following a diagnosis of a gynaecological cancer.
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PMID:Psychosexual function and impact of gynaecological cancer. 1719 33

Women dying of ovarian cancer vary considerably in their complications and in the types of health care they receive. The objective of this study was to describe the complications of ovarian cancer, other than pain, and their treatment at the end of life. This study used a cohort of 421 enrollees in three nonprofit managed-care organizations who died with ovarian cancer during 1995-2000. Data were collected from abstraction of paper and electronic medical records. Proportions of women experiencing complications and undergoing treatments were calculated. Logistic regression was used to evaluate the association of patient characteristics with the probability of receiving an intervention for complications. The most common complications recorded in the medical record were fatigue or weakness (75%), nausea or vomiting (71%), constipation (49%), edema of the extremities (44%), and anemia (34%). The prevalence of major complications was as follows: ascites, 28%; bowel obstruction, 12%; pleural effusion, 10%; bladder obstruction, 3%; and disordered nutrition that required support with parenteral nutrition, 9%. Patients may not always have received interventions for major complications; for example, pleural effusion apparently was left untreated in almost half of the women with this problem. After adjustment, women who died at younger ages were more likely to receive an intervention, compared to older women (odds ratio for each decade of age, 0.71, 95% confidence interval=0.53, 0.94, P for trend=0.02). The study, which preceded the establishment of palliative care programs, suggests that care given to ovarian cancer patients at the end of life may be inadequate.
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PMID:Complications at the end of life in ovarian cancer. 1760 60


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