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)

Clinical study has been conducted to evaluate the efficacy of chemotherapy with docetaxel and cisplatin in six patients with advanced non-small cell lung cancer. Treatment schedule consisted of docetaxel 60 mg/m2 and cisplatin 80 mg/m2 on day 1 and repeated every 4 weeks. Eligible patients had histologically proven locally advanced or metastatic non-small cell lung cancer, PS < or = 2, age < or = 74, normal hematological, hepatic and renal functions and informed consent in writing. Six patients have been included; all were males, median age 64 (range 47-74), histology; adenocarcinoma 4, squamous cell carcinoma 2, stage III B 4, stage IV 2. Among these 6 patients, 3 PR (50%) were observed. Neutropenia was the most common adverse event (83%). The lowest granulocyte counts were most frequently seen on day 9.4 (range: 6-14). Non hematologic adverse events included alopecia (6 cases), general fatigue (5 cases), anorexia (5 cases) and emesis (3 cases). These events were recovered rapidly with no therapy. The results suggest that combination chemotherapy of docetaxel and cisplatin will be effective and safe under careful observation.
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PMID:[Evaluation of chemotherapy with docetaxel and cisplatin in advanced non-small cell lung cancer]. 1039 19

Resistance may be classified as active (or competitive) (due to excess amount of a factor) vs passive (or non-competitive) (due to a deficiency of a factor). Passive resistance may be important in human solid tumors. In passive resistance, the dose-response curve may be shallow, or may flatten at a relatively low dose. We hypothesized that, if passive resistance were important, it might be advantageous to use low doses of multiple concurrent chemotherapy agents with differing mechanisms of action, rather than using high doses of 2 or 3 drugs. We combined single day cisplatin 60 mg/m2, cyclophosphamide 250 mg/m2, epirubicin 40 mg/m2, paclitaxel 60 mg/m2, and vinblastine 2.5 mg/m2, with 5 days of 5-fluorouracil 200 mg/m2, folinic acid 20 mg/m2 and dexamethasone 4 mg orally q.i.d. every 3 weeks. In later cohorts, doses were escalated, and tamoxifen and verapamil were added. Twenty-three patients were entered. ECOG performance status was 1 in 15 patients and 2 in 8. Number of prior chemotherapy regimens was 0 in 4 patients, 1 in 4, 2 in 8, 3 in 4, 4 in 2, and 7 in 1. Sixteen patients had prior radiotherapy, and 3 had no prior therapy. Myelosuppression and febrile neutropenia were frequent, and 4 heavily pretreated patients died of pneumonia contracted while neutropenic. Diarrhea, nausea and vomiting, and fatigue were also prominent. Among 9 patients with non-small cell lung cancer, one had a partial remission, 4 had stable disease (including 3 with minor objective responses). Two additional non-small cell lung cancer patients also had objective tumor regression, but were coded as failures, since one had tumor progression in <6 weeks and the other died of respiratory failure (thought to be due to severe mucous plugging) one week after his first course of treatment. Among 14 patients with other tumor types, there was one partial response (esophageal carcinoma), 6 patients with stable disease for >6 weeks (including minor responses in one patient each with adenocarcinomas of kidney and breast), and 7 failures (including one patient with adenocarcinoma unknown primary who had minor tumor regression lasting 4 weeks). Despite the unacceptably high toxic death rate, median survival time was 24 weeks (range, 1 week to >104 weeks). This regimen is toxic, but survival duration is longer than would be expected in this heavily pre-treated population. Doses recommended for further study are those used in the first treatment cohort (as described above). Since myelosuppression is the major toxic effect, hemopoietic growth factors might prove helpful with this regimen.
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PMID:Concurrent use of multiple low dose chemotherapy agents with differing mechanisms of action as a strategy vs passive resistance: A pilot study. 1049 50

The principal objectives of this trial were twofold: (a) to examine the safety and relative efficacy of intradermal needle injection versus s.c. jet administration of a carcinoembryonic antigen (CEA)-encoding recombinant vaccinia virus (rV-CEA) over a limited dose range and (b) to evaluate CEA-specific immune responses or antitumor effects induced by rV-CEA vaccination. Patients were randomly assigned to one of two groups, depending upon the technique of vaccine administration. All 20 patients received two doses of 10(7) or 10(8) pfu of rV-CEA at a 4-week interval. Toxicity was limited to modest local inflammation at the inoculation site as well as low-grade fever and increased fatigue, each affecting fewer than 20% of the patients. No evidence of CEA-specific lymphoproliferation, interleukin 2 release, delayed-type hypersensitivity, or antibody response was observed. Thus, the efficacy comparison between the two administration techniques was based upon the induction of immune responses to the vaccinia virus vector. Both techniques induced vaccinia-specific lymphoproliferation, interleukin 2 release, and antibody responses of comparable magnitude and frequency as well as protected 80% of patients against pustule formation following vaccinia scarification. Thus, there is no compelling reason to recommend one administration technique over the other based upon toxicity or efficacy. We have selected s.c. jet injection for subsequent trials of rV-CEA based on the ability to accommodate larger injection volumes, enhanced standardization between clinicians, and avoidance of needles that could transmit the vaccine or blood-borne pathogens to health care workers. We recommend use of 10(8) pfu doses for subsequent trials of recombinant vaccinia virus vaccines based upon the favorable toxicity profile and more consistent local pustule formation indicative of an adequate inoculation of live virus. No objective clinical responses to the rV-CEA vaccine were observed among this population of patients with widely metastatic adenocarcinoma.
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PMID:Phase I trial of a recombinant vaccinia virus encoding carcinoembryonic antigen in metastatic adenocarcinoma: comparison of intradermal versus subcutaneous administration. 1049 1

We describe here a rare case of hepatoid adenocarcinoma (HAC) of the gallbladder without the production of alpha-fetoprotein (AFP). A 77-year-old man was referred to our division with complaints of general fatigue, loss of appetite, and loss of body weight. A preoperative diagnosis of advanced gallbladder cancer was made, and cholecystectomy with combined resection of two liver subsegments (S4a + S5) and lymph node dissection were performed. Microscopically, the tumor was mainly composed of characteristic cells featuring eosinophilic cytoplasm, enlarged nuclei, and prominent nucleoi, arranged in nests or proliferated in a trabecular pattern. These features were highly suggestive of HAC of the gallbladder, and the tumor cells were negative for AFP immunohistochemical staining. The patient is doing well and has survived for 15 months postoperatively without any recurrence.
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PMID:Hepatoid adenocarcinoma of the gallbladder. 1098 19

A case of decisive material degeneration of an esophageal Celestin tube is described: a 50-year-old man with adenocarcinoma of the distal esophagus received a Celestin tube for palliative endoscopic treatment and 8 months later presented with suddenly occurring complete dysphagia. Dissolution of the latex layer in the proximal as well as the distal part of the tube had caused self-disintegration of the Celestin tube and had liberated the monofilament nylon coil which completely obstructed the lumen of the tube. Endoscopic tube removal was only possible by careful attachment of a balloon catheter and peroral extraction after insufflation with contrast medium up to 5 atm. A Medline-based review of the literature revealed different but predominantly severe complications (perforation, hemorrhage, obstruction, and peritonitis) based on material fatigue of the latex layer in esophageal Celestin tubes. At least 6 months after placement of a Celestin tube, regular fluoroscopic controls should be performed to detect early disintegration of the tube. Indication for the placement of Celestin tubes in patients with benign esophageal strictures and longer life expectancy should be assessed very critically.
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PMID:Severe complications caused by dissolution of latex with consequent self-disintegration of esophageal plastic tubes. 1139 70

A phase II study was conducted to assess the response rate and toxicity profile of the combination of irinotecan (CPT-11, Camptosar) and cisplatin (Platinol) administered weekly to patients with untreated advanced adeno-carcinoma of the stomach or gastroesophageal junction. Patients with histologic proof of adenocarcinoma of the stomach or gastroesophageal junction and with adequate liver, kidney, and bone marrow functions were included. Patients were treated with 65 mg/m2 of irinotecan plus 30 mg/m2 of cisplatin, both administered intravenously 1 day per week for 4 consecutive weeks, followed by a 2-week recovery period. Response rate, time to progression, survival, and toxic effects were analyzed. Thirty-six (95%) of 38 registered patients were assessable for toxicity and response. The median number of 6-week cycles per patient was 2.5 (range: 1 to 7 cycles). Four patients (11%) achieved a complete response and 17 (47%) had a partial response for an overall response rate of 58%. Median time to progression of carcinoma was 24 weeks, and median survival was 9 months (range: 1 to 23+ months). There was one treatment-related death. Major toxic effects included diarrhea, neutropenia, and fatigue. The combination of irinotecan and cisplatin is active against gastric or gastroesophageal adenocarcinoma and should undergo further study. The addition of other active drugs or radiation therapy to this regimen would be of interest.
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PMID:Irinotecan plus cisplatin in advanced gastric or gastroesophageal junction carcinoma. 1130 42

Gemcitabine has modest activity in the treatment of advanced pancreatic cancer and is a potent radiosensitizer. We conducted a Phase I trial to determine the maximum tolerated dose of weekly gemcitabine delivered concurrently with radiation therapy for the treatment of locally advanced adenocarcinoma of the pancreatic head and to assess the treatment-related toxic effects associated with such a regimen. Eighteen patients with pathologically proven, locally advanced adenocarcinoma of the pancreatic head were enrolled in this study. Patients received seven weekly doses of gemcitabine with 3000 cGy of external beam radiation therapy delivered during the first 2 weeks of therapy. Six patients received gemcitabine at 350 mg/m(2)/week, nine at 400 mg/m(2)/week, and three at 500 mg/m(2)/week. Grade 3-4 hematological toxicity was observed in over half the patients treated. Nonhematological toxicities were significant and included fatigue, anorexia, nausea, vomiting, and dehydration. Forty-four % of the patients required admission to the hospital for management of nausea/vomiting and dehydration. The risk of hospitalization appeared to be dose-related; all of the three patients treated at 500 mg/m(2)/week required hospital admission during treatment. Seventeen patients were evaluated for response, and eight patients (47%) had evidence of a local anticancer effect. Four of these eight patients (24%) had a partial response to therapy. The median survival for the entire group was 6 months. The 1-year survival rate for patients with an objective response to therapy was 66%. The clinical responses observed in this group of patients suggest gemcitabine is a clinically relevant radiosensitizer in patients with pancreatic adenocarcinoma. However, the toxic effects are significant, suggesting that until dose and scheduling issues are explored further, concomitant administration of gemcitabine and radiation therapy should still be considered investigational.
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PMID:Phase I trial of gemcitabine combined with radiation for the treatment of locally advanced pancreatic adenocarcinoma. 1148 98

A 69-year-old woman was admitted to our hospital because of anal bleeding and fatigue. The patient was previously diagnosed as having Evans' syndrome on the basis of hematological examination and had been treated with predonisolone for 8 years. On admission, severe anemia and thrombocytopenia were noted. Colonoscopy and Barium enema studies demonstrated an irregular tumor with hemorrhagic ulceration in the rectum, which was histopathologically confirmed as an adenocarcinoma. After red blood cells and platelets were transfused, and the patient was treated with high-dose gammaglobulin, predonisolone, and camostat mesylate, the platelet count gradually increased and hemolysis was well controlled. The patient then underwent Hartmann's operation and splenectomy without any postoperative complications. Predonisolone and high-dose immunoglobulin therapy in a rectal cancer burdened patient with Evans' syndrome is considered useful in combination with surgical treatment. This is the first case report of rectal carcinoma resection in a patient with Evans' syndrome.
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PMID:Successful resection of rectal carcinoma in an Evans' syndrome patient followed by predonisolone and high-dose immunoglobulin: report of a case. 1151 68

The aim of this study was to test the efficacy of a chemotherapy combination of cisplatin, IFN alpha-2b, doxorubicin, Adriamycin, and 5-fluorouracil (PIAF) as treatment for radiologically measurable cancer of the biliary tree. Forty-one patients (19 gallbladder carcinoma and 22 cholangiocarcinoma) with unresectable, histologically confirmed adenocarcinoma were registered. Starting chemotherapy doses were as follows: cisplatin, 80 mg/m(2) i.v. over 2 h; doxorubicin, 40 mg/m(2) i.v. over 2 h; and 5-fluorouracil, 500 mg/m(2) by continuous infusion daily for 3 days. IFN alpha-2b (5 x 10(6) units/m(2)) was administered s.c. before the cisplatin and daily thereafter for a total of four doses. The overall response rate was 21.1% [95% confidence interval (CI), 10-37]. For cholangiocarcinoma and gallbladder carcinoma patients, the response rates were 9.5% (95% CI, 1-32%) and 35.3% (95% CI, 14-62%), respectively. Overall median survival time was 14 months (95% CI, 9.5-18.5), 18.1 months (95% CI, 12.1-24.1) for the cholangiocarcinoma patients, and 11.5 months (95% CI, 5.9-17.1) for the gallbladder carcinoma patients. This difference was not statistically significant. The most common grade III and IV toxicities were neutropenia (41%), thrombocytopenia (20%), nausea and vomiting (34%), and fatigue (20%). In conclusion, the PIAF combination seemed more active against gallbladder carcinoma than against cholangiocarcinoma but was associated with significant toxicity. Therefore, this regimen cannot be recommended for cholangiocarcinoma, but it may have a role in the treatment of gallbladder carcinoma, particularly among patients who were refractory to higher priority investigational agents.
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PMID:Phase II trial of cisplatin, interferon alpha-2b, doxorubicin, and 5-fluorouracil for biliary tract cancer. 1170 50

Most neoplasms arising from the thymic epithelium are considered to be 'thymomas', which are composed of cytologically benign, neoplastic epithelial cells and nonneoplastic lymphocytes. In contrast, thymic epithelial neoplasms displaying cytologically malignant features have recently been classified as thymic carcinomas of various types of histology. However, primary thymic adenocarcinoma is extremely rare and only four cases of it have been reported in the literature. We report a rare case of primary thymic adenocarcinoma of 4-year complete remission with concurrent chemoradiotherapy followed by surgery. A 61-year-old Japanese man was referred to us complaining of facial edema and general fatigue. Computed tomography scans revealed a huge mass in the anterior mediastinum obstructing the superior vena cava. He was diagnosed with thymic adenocarcinoma on needle biopsy. He was treated with induction chemoradiotherapy consisting of cisplatin, 5-FU and concurrent thoracic radiation, which yielded a partial response. He then underwent surgical resection of the remaining mass. However, pathologic examination of the resected mass revealed no malignant cells. The patient is doing well without symptoms or signs of relapse 53 months after diagnosis.
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PMID:Successful treatment with concurrent chemoradiotherapy followed by surgery for a patient with thymic adenocarcinoma. 1172 16


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