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 present the results of a phase 2 study using thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) in the treatment of 50 patients older than 65 years with newly diagnosed multiple myeloma. Thalidomide 100 mg was administered orally at bedtime continuously, dexamethasone 40 mg was administered orally on days 1 to 4 and 9 to 12, and pegylated liposomal doxorubicin 40 mg/m2 was administered intravenously on day 1 over the 28-day cycle. Response was assessed according to the EBMT criteria. Seventeen (34%) patients achieved CR, 7 (14%) nCR, 5 (10%) VGPR, 15 (30%) PR, and 5 (10%) MR, resulting in an ORR of 98%. Only 1 patient (2%) presented progressive disease. Time to progression (TTP), event-free survival (EFS), and overall survival (OS) projected at 3 years were 60%, 57%, and 74%, respectively, and these parameters were significantly higher in those patients achieving a response of at least VGPR versus those who did not. Grade 3 and 4 nonhematologic adverse events were constipation (10%), fatigue (6%), tremors (4%), mucositis (4%), and palmar-plantar erythrodysesthesia (2%). Grade 3 and 4 neutropenia occurred in 12% of patients. Grade 3 and 4 infections and thromboembolic accidents were observed in 22% and 14% of patients, respectively. In the treatment of elderly patients with newly diagnosed multiple myeloma, ThaDD is a very effective regimen with manageable toxicity.
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PMID:Thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) for patients older than 65 years with newly diagnosed multiple myeloma. 1676 9

The aim of the study was to obtain United Kingdom-based societal preferences for distinct stages of metastatic breast cancer (MBC) and six common toxicities. Health states were developed based on literature review, iterative cycles of interviews and a focus group with clinical experts. They described the burden of progressive, responding and stable disease on treatment; and also febrile neutropenia, stomatitis; diarrhoea/vomiting; fatigue; hand-foot syndrome (grade 3/4 toxicities) and hair loss. One hundred members of the general public rated them using standard gamble to determine health state utility. Data were analysed with a mixed model analysis. The study sample was a good match to the general public of England and Wales by demographics and current quality of life. Stable disease on treatment had a utility value of 0.72, with a corresponding gain of +0.07 following a treatment response and a decline by 0.27 for disease progression. Toxicities lead to declines in utility between 0.10 (diarrhoea/vomiting) and 0.15 (febrile neutropenia). This study underlines the value that society place on the avoidance of disease progression and severe side effects in MBC. This may be the largest preference study in breast cancer designed to survey a representative general public sample.
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PMID:Health state utilities for metastatic breast cancer. 1696 55

We retrospectively evaluated acute toxicity in 88 patients that were treated with capecitabine and concurrent radiotherapy to the upper abdomen. These patients included 28 (32%) with pancreatic adenocarcinoma, 18 (20%) with cholangiocarcinoma, 11 (13%) with ampullary carcinoma, 11 (13%) with other primary tumors, 14 (16%) with liver metastases, and 6 (7%) with metastases at other sites. The median dose of radiotherapy was 45 Gy (range 30-72 Gy). The median dose of capecitabine was 850 mg/m(2) twice daily, with 77% receiving 800-900 mg/m(2) twice daily. The highest grade of acute toxicity was Common Terminology Criteria (CTC) grade 0 in 5 (6%), grade 1 in 60 (68%), grade 2 in 18 (20%), and grade 3 in 5 (6%) patients. No patient had CTC grade 4 toxicity. The most common grade 2 toxicities were nausea, hand-foot syndrome, fatigue, anorexia and diarrhea. The grade 3 toxicities included nausea, vomiting and fatigue. Three patients (3%) required hospitalization due to grade 3 acute toxicity. Capecitabine was interrupted, discontinued or given at an adjusted dose in 13 (15%) patients because of acute toxicity. Therefore, capecitabine and concurrent radiotherapy to the upper abdomen appears to be well tolerated. Capecitabine may serve as an alternative to bolus or infusional 5-FU during chemoradiation for upper gastrointestinal malignancies.
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PMID:Concurrent capecitabine and upper abdominal radiation therapy is well tolerated. 1706 48

This phase II study assessed the safety and efficacy of oxaliplatin and capecitabine in patients with advanced oesophageal cancer. Fifty-one eligible patients received oxaliplatin 130 mg m(-2) intravenously on day 1 and capecitabine 1000 mg m(-2) orally twice daily on days 1 to 14 in a 21-day treatment cycle as first-line treatment for advanced oesophageal cancer. Grade 3 neutropenia was seen in one patient and anaemia in another patient. No grade 4 haematological toxicities were observed. Grade 4 non-haematological toxicity (lethargy) occurred in one patient (2%). Grade 3 non-haematological toxicity was seen in 14 (27%) patients (vomiting and polyneuropathy (8%); nausea (6%); lethargy and hand-foot syndrome (4%); and anorexia, diarrhoea, and hyperbilirubinaemia (each in one patient)). In 22% of the patients, toxicity was the reason for stopping the treatment. The overall response rate was 39%. The median overall survival was 8 months; the 1-year survival rate was 26%. In the quality of life (QoL) analysis, the emotional well-being improved during treatment, but the physical functioning scores declined. The fatigue score on the symptom scales increased. Overall, the global QoL score did not change during treatment. In conclusion, the activity of oxaliplatin and capecitabine is comparable with other chemotherapy regimens in advanced oesophageal cancer with a low frequency of grade 3/4 toxicity. Because this treatment can be given on an outpatient basis, it is probably less toxic than cisplatin-based therapy and preserves QoL during treatment, it is a viable treatment option in patients with advanced oesophageal cancer.
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PMID:First-line treatment with oxaliplatin and capecitabine in patients with advanced or metastatic oesophageal cancer: a phase II study. 1743 8

Three patients with advanced renal-cell cancer were treated with sunitinib 50 mg daily for 4 weeks followed by a rest period of 2 weeks because of progressive disease. The first patient developed stomatitis and a painful blister on his foot. Complaints disappeared after temporary discontinuation of treatment. Re-treatment at a lower dosage was successful until disease progression. The second patient developed skin discolouration, fatigue, fever and diarrhoea. After treatment was interrupted shortly, these symptoms disappeared and sunitinib was recommenced at a lower dosage. The patient went on to develop stomatitis, thrombocytopenia and hypertension (treated with amlodipine). She subsequently had hand-foot syndrome. She died due to brain metastases. In the third patient symptoms of disease returned during the rest period, because of which he received a reduced dosage of sunitinib on a continuous base. He developed diarrhoea which disappeared after a short interruption of the drug. Sunitinib has been approved for the treatment of advanced renal-cell cancer and imatinib-resistant gastro-intestinal stromal tumours. This novel targeting molecule is a tyrosine-kinase inhibitor of vascular endothelial growth-factor receptors, platelet-derived growth-factor receptors and c-Kit. It can induce adverse events that differ from those observed in treatment with conventional cytotoxic agents. The adverse effects are reduced by lowering the dosage and in the rest period within the treatment cycle.
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PMID:[Adverse effects of the tyrosine-kinase inhibitor sunitinib, a new drug for the treatment of advanced renal-cell cancer]. 1755 72

Renal cell cancer (RCC) is a relatively uncommon malignancy, with 51,190 cases expected to be diagnosed in 2007. Localized disease is curable by surgery; however, locally advanced or metastatic disease is not curable in most cases and, until recently, had a limited response to drug treatment. Historically, biologic response modifiers or immunomodulating agents were tested in clinical trials based on observations that some cases of RCC can spontaneously regress. High-dose aldesleukin is approved by the United States Food and Drug Administration as a treatment for advanced RCC; however, the drug is associated with a high frequency of severe adverse effects. Responses have been observed with low-dose aldesleukin and interferon alfa, but with little effect on overall survival. Sorafenib and sunitinib are novel therapies that target growth factor receptors known to be activated by the hypoxia-inducible factor and the Ras-Raf/MEK/ERK pathways. These pathways are important in the pathophysiology of RCC. Sorafenib and sunitinib have shown antitumor activity as first- and second-line therapy in patients with cytokine-refractory metastatic RCC who have clear-cell histology. Although complete responses are not common, both drugs promote disease stabilization and increase progression-free survival. This information suggests that disease stabilization may be an important determinant for response in RCC and possibly other cancers. Sorafenib and sunitinib are generally well tolerated and are considered first- and second-line treatment options for patients with advanced clear cell RCC. In addition, sorafenib and sunitinib have shown promising results in initial clinical trials evaluating antitumor activity in patients who are refractory to other antiangiogenic therapy. The most common toxicities with both sorafenib and sunitinib are hand-foot syndrome, rash, fatigue, hypertension, and diarrhea. Research is directed toward defining the optimal use of these new agents.
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PMID:Sorafenib and sunitinib: novel targeted therapies for renal cell cancer. 1765 13

S-1 is an oral fluoropyrimidine consisting of the 5-fluorouracil prodrug tegafur combined with two modulating substances, gimeracil and potassium oxonate. On the basis of the potential additive effect between mitomycin C (MMC) and 5-fluorouracil as a continuous infusion, we conducted a phase II study to assess the efficacy and tolerability of the combination of S-1 and MMC as second-line chemotherapy for advanced gastric cancer (AGC). Patients with measurable AGC, progressive after one prior chemotherapy for metastatic disease, received MMC (7 mg/m2) on day 1 and S-1 (40 mg/m2) twice daily as an intermittent regimen of 4 weeks of treatment followed by a 2-week rest. Treatment was repeated every 6 weeks. The primary objective was the response rate. For 43 patients registered, 42 patients were treated with MMC plus S-1. A total of 121 chemotherapy cycles were delivered (median: 2; range: 1-6). The patients' median age was 53 years (range: 31-75) and nine (21%) had an Eastern Cooperative Oncology Group performance status of 2. In an intent-to-treat analysis, nine patients (21%) achieved an objective response, which was maintained for 4.1 months. The median progression-free and overall survivals were 3.4 months (95% confidence interval: 2.3-4.5) and 8.0 months (95% confidence interval: 6.1-9.9), respectively. Although fatigue was the most frequently encountered toxicity safety profiles were generally predictable and manageable. One patient developed hemolytic anemia, which was resolved spontaneously. Grade > or = 2 hand-foot syndrome was observed in only three patients. Second-line chemotherapy with MMC and S-1 is an active and tolerable regimen for AGC patients with good performance status.
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PMID:Mitomycin C plus S-1 as second-line therapy in patients with advanced gastric cancer: a noncomparative phase II study. 1851 Jan 77

Axitinib is an oral inhibitor of the VEGF, PDGF and colony stimulating factor-1 receptor tyrosine kinases and is currently in development by Pfizer Inc for the potential treatment of various solid tumors. Phase II trials with this agent alone or in combination with chemotherapeutic drugs were reported in several types of malignancy, with activity observed in thyroid, pancreatic, lung, renal, breast and colorectal cancers, melanoma and other carcinomas. Although frequent side effects have included fatigue, hypertension, diarrhea, hand-foot syndrome and proteinuria, axitinib was well tolerated overall. Larger, randomized phase II/III studies were ongoing at the time of publication.
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PMID:Axitinib, a novel anti-angiogenic drug with promising activity in various solid tumors. 1851 65

Sunitinib has been registered for the treatment of advanced renal cell cancer (RCC). As patient inclusion was highly selective in previous studies, experience with sunitinib in general oncological practice remains to be reported. We determined the efficacy and safety of sunitinib in patients with advanced RCC included in an expanded access programme. ECOG performance status >1, histology other than clear cell and presence of brain metastases were no exclusion criteria. Eighty-two patients were treated: 23% reached a partial response, 50% had stable disease, 20% progressed and six patients were not evaluable. Median progression-free survival (PFS) was 9 months and median overall survival (OS) was 15 months. Importantly, 47 patients (57%) needed a dose reduction, 35 (43%) because of treatment-related adverse events, 10 (12%) because of continuous dosing, and two because of both. Stomatitis, fatigue, hand-foot syndrome and a combination of grade 1-2 adverse events were the most frequent reasons for dose reduction. In 40 patients (49%), there was severe toxicity, defined as dose reduction or permanent discontinuation, which was highly correlated with low body surface area, high age and female gender. On the basis of age and gender, a model was developed that could predict the probability of severe toxicity.
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PMID:Predictive factors for severe toxicity of sunitinib in unselected patients with advanced renal cell cancer. 1975 85

Patients with colorectal cancer present a number of supportive care challenges including those related to the underlying disease, such as gastrointestinal obstruction, nausea, anorexia, and fatigue, and those caused by the treatments, such as oral mucositis, neuropathy, and chemotherapy-induced diarrhea. Unique toxicities can accompany specific routes of administration of colon cancer drugs such as hand-foot syndrome with oral capecitabine and continuous infusion fluorouracil and biliary sclerosis with intrahepatic arterial floxuridine. The newer targeted therapies also present new toxicities, such as cardiovascular events and wound-healing complications with bevacizumab and rash and hypomagnesemia with cetuximab. Recent additions to the therapeutic armamentarium have presented new challenges, such as oxaliplatin-induced peripheral neuropathy, capecitabine-induced hand-foot syndrome, cetuximab-induced rash, and bevacizumab-associated arterial thrombotic events, bowel perforation, hypertension, and wound-healing complications. This article focuses on the prevention and management of several of these more common symptoms and toxicities.
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PMID:Supportive care in the management of colon cancer. 1863 90


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