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

Broad phase II trial of methylglyoxal-bi (guanylhydrazone) (MGBG) is under way at the Memorial Sloan-Kettering Cancer Center. Studies in renal cell carcinoma, lymphomas, and non-small-cell lung cancer are completed, and substantial numbers of patients with esophageal and head and neck cancer have been treated. Small numbers of patients with other solid tumors have also been entered into the study. MGBG has significant antineoplastic activity against lymphomas, with 16/40 heavily pretreated patients (40%) having partial remissions (PR) lasting 1 to 8+ months. MGBG has also demonstrated more modest activity in non-small-cell lung cancer, esophageal, and head and neck carcinoma; it appears to have little or no therapeutic value in renal cell cancer. Toxicities have been manageable, and included mild nausea and vomiting, diarrhea, mucositis, and myelosuppression. The dose-limiting toxicity, seen most frequently in those patients with impaired renal function, was lethargy and fatigue. MGBG has demonstrated activity in lymphomas, lung, esophageal, and head and neck cancer. Further trials of this agent are indicated, both alone and in combination.
 ...
PMID:Phase II trials of methylglyoxal-bis (guanylhydrazone). 704 14

Since cytotoxic chemotherapy (BCNU, DTIC and cisplatin, tamoxifen) and interferon-alpha (IFN-alpha) have each produced responses in advanced malignant melanoma, a phase II trial was conducted to evaluate the response and toxicity of simultaneous administration of both therapies. Of 33 assessable patients, two (6%) had complete response (CR) and 12 patients (36%) had partial response (PR), for a total response rate (CR+PR) of 42% (95% confidence interval 26-58). Four patients had minor response (12%). Mixed responses occurred in five patients (15%). The remaining patients had progressive disease. The duration of CR was 3, 7 and 17 (+) months and the duration of PR was 3+ to 19+ months (median 6 months). The median overall survival for all patients entered into the study was 5 months. Main toxicities included myelosuppression and fatigue. Combined simultaneous cytotoxic chemotherapy and IFN produced a high response rate (42%) which is comparable to that reported for chemotherapy alone. Further studies are needed to determine the optimal schedule for combining chemotherapy and immunotherapeutic agents as well as the impact of biological agents on survival in the treatment of melanoma.
 ...
PMID:Phase II trial of recombinant interferon-alpha with BCNU, cisplatin, DTIC and tamoxifen in advanced malignant melanoma. 749 64

Since their initial description in 1957, the interferons (IFNs) have been increasingly used to treat a wide array of diseases. Acute adverse effects, i.e. 'flu-like' syndromes, hypo- or hypertension, tachycardia, headache, myalgias and gastrointestinal disorders, occur within the first hour or day after starting treatment. They are seldom treatment-limiting and are easily manageable. Sub-acute and chronic effects develop after several days, usually within 2 and 4 weeks of therapy. The most typical is neurological toxicity, including fatigue/asthenia, and behavioural and cognitive changes. Such symptoms may seriously impair quality of life and result in treatment discontinuation. Seizures have seldom been described. Other infrequent central nervous system adverse effects include vertigo, cramp and oculomotor nerve paralysis. Distal paraesthesias and peripheral neuropathy have been reported. IFN-associated autoimmunity is quite rare but a matter of concern. Biological or clinical manifestations usually require several months to become apparent. Autoantibodies have been shown to develop in most patients but have been inconsistently associated with clinical symptoms of systemic lupus erythematosus, rheumatoid-like arthritis and thyroiditis. Both hypo- and hyperthyroidism have been described but are usually reversible. Other infrequent autoimmune reactions include diabetes, pemphigus and worsening of multiple sclerosis. Although several patients present with a pre-existing autoimmune disorder, no predisposing factor has been clearly established. While hypotension and tachycardia are the most frequent acute cardiovascular complications, a few additional cases of cardiac arrhythmias and myocardial ischaemia have been reported after a short course or several weeks of treatment. These latter complications do not appear to be dose-dependent or age-related. Isolated cases of congestive heart failure have also been described. Mild proteinuria has been observed in 15 to 25% of patients, but acute renal toxicity is uncommon. A transient rise in serum aminotransferase levels is frequently noted during the first stage of therapy, especially in patients receiving the highest dosages. Direct hepatotoxicity is extremely rare. Autoimmune hepatitis, which is ill-diagnosed as chronic viral hepatitis, and de novo induction of autoimmune hepatitis, account for the majority of liver diseases. Haematotoxicity is relatively common but mild to moderate, and develops gradually during the first weeks of treatment. Neutropenia is the most common haematological toxicity, but is usually not dose-limiting and resolves rapidly upon drug discontinuation. Myelosuppression, autoimmune and immune allergic haemolytic anaemias and thrombocytopenias have seldom been described. Cutaneous adverse effects comprised nonspecific erythema and hair loss and, less frequently, vasculitis, local ulcerations at the site of injection and exacerbation of psoriasis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Clinical toxicity of the interferons. 751 63

Based on the superior response rates (21% to 24%) of patients treated with single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in Eastern Cooperative Oncology Group and M.D. Anderson Cancer Center trials in non-small cell lung cancer (NSCLC) and on the superior 1-year survival rates of NSCLC patients treated with carboplatin in a randomized study of cisplatin combination and analogues, we initiated a phase II trial of paclitaxel/carboplatin in patients with stage IV or effusion-positive stage III NSCLC. Eligibility stipulated chemotherapy-naive patients with measurable disease, good performance status, and adequate hematologic, hepatic, and renal function. Previous radiotherapy was restricted to < or = 30% of marrow-bearing bone. Paclitaxel was initially given at 135 mg/m2 over 24 hours followed by carboplatin dosed to a targeted area under the concentration versus time curve (AUC) of 7.5, with treatment repeated at 3-week intervals for six cycles. Granulocyte colony-stimulating factor was introduced during the second and subsequent cycles, with the paclitaxel dose sequentially escalated in 40 mg/m2 increments to a maximum dose of 215 mg/m2 in patients with less than grade 4 granulocytopenia and less than grade 3 thrombocytopenia. Of 54 patients enrolled, 30 currently are evaluable for response, 23 for toxicity. Myelosuppression has been the principal toxicity, with grade 3 or 4 granulocytopenia occurring in 70% of patients after the first cycle. After the introduction of granulocyte colony-stimulating factor, granulocytopenia decreased to 37% during the second cycle and then consistently to 20% or lower during subsequent cycles. Only 22% of cycles have been delayed for 1 week or more. Neutropenic fever has occurred in five (5%) of 100 evaluable cycles. Other grade 3 or 4 toxicities include thrombocytopenia (13%), anemia (9%), fatigue (9%), and hemorrhagic cystitis (1%). The paclitaxel dose was boosted to 215 mg/m2 in 12 (70%) of 17 patients by cycle 3 or 4. At an AUC of 7.5, the median first-cycle carboplatin dose was 434 mg/m2 (range, 293 to 709 mg/m2). The objective response rate is 50%, with three complete, 12 partial, and five minor responses. We conclude that the paclitaxel/carboplatin combination is active in advanced NSCLC and, with AUC-based dosing of carboplatin, can be given at 3-week intervals. Although dose limiting at a paclitaxel dose of 135 mg/m2, granulocytopenia can be reduced substantially with granulocyte colony-stimulating factor, allowing sequential dose escalation of paclitaxel to 175 mg/m2 and 215 mg/m2 in 70% of patients receiving three or more cycles.
 ...
PMID:Paclitaxel and carboplatin in the treatment of advanced non-small cell lung cancer. 754 Nov 56

A phase II trial of combination paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin included 54 chemotherapy-naive patients with advanced non-small cell lung cancer. Eligibility mandated Eastern Cooperative Oncology Group performance status of 0 or 1 and adequate hematologic, renal, and hepatic function. Paclitaxel 135 mg/m2 over 24 hours preceded carboplatin dosed to an area under the concentration-time curve of 7.5. Six planned courses were given every 3 weeks. Granulocyte colony-stimulating factor was introduced during the second and subsequent cycles, and paclitaxel increased 40 mg/m2/cycle (maximum, 215 mg/m2) in patients with absolute neutrophil and platelet nadirs exceeding 500/microL and 50,000/microL, respectively. Grade 3 or 4 neutropenia, observed in 54% of patients during cycle 1, declined to 35% during cycle 2 and to 22% or less during cycles 3 through 6. Neuropathy, myalgias/arthralgias, and thrombocytopenia were mild but cumulative. In 53 evaluable patients, the objective response rate was 62%, with 9% complete remissions and a median response duration of 6 months (range, 1 to 19+ months). At median potential follow-up of 16 months, 9% of patients remain progression free (52+ to 80+ weeks). Median survival is 12.5 months; 1-year survival is 54%. Paclitaxel/carboplatin is highly active in advanced non-small cell lung cancer; granulocyte colony-stimulating factor abrogates neutropenia as the dose-limiting toxicity, but has no effect on the cumulative incidence of thrombocytopenia or treatment delays. One-hour paclitaxel infusion is minimally myelosuppressive, logistically easier, and less costly. A follow-up study combined paclitaxel (175 mg/m2) over 1 hour followed by carboplatin (area under the concentration-time curve, 7.5). In the absence of grade 4 myelosuppression, paclitaxel was increased 35 mg/m2/cycle (maximum, 280 mg/m2). Granulocyte colony-stimulating factor was implemented only after neutropenic fever or grade 4 neutropenia. Of 17 patients entered, 13 are evaluable for toxicity and seven for response. Four patients have sustained a partial response, two a minor response, and one stable disease. The incidence of grade 3 or 4 neutropenia, thrombocytopenia, and anemia in cycle 1 was 38%, 16%, and 0%, respectively, and 72%, 28%, and 28%, respectively, during cycle 2. Major nonhematologic toxicities include myalgias and arthralgias (54%) and fatigue and neuropathy (78%), the latter cumulative and progressive over successive cycles. Preliminary data suggest comparable activity for the 1- and 24 hour paclitaxel infusions in combination with carboplatin. The more severe neuropathy of the 1-hour paclitaxel/carboplatin combination may be related to the paclitaxel dosing schema (175 mg/m2 to as high as 280 mg/m2).(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Paclitaxel by 24- or 1-hour infusion n combination with carboplatin in advanced non-small cell lung cancer: the Fox Chase Cancer Center experience. 754 25

Methoxymorpholinyldoxorubicin (FCE 23762) is a novel, highly lipophilic doxorubicin analogue. It possesses potent in vitro and in vivo antitumor activity including efficacy in multidrug-resistant tumor cell lines. It is also metabolically activated in vivo resulting in an 80-fold increase in potency over the parent drug. In this phase I study the drug was administered by i.v. bolus injection at 3-week intervals. Fifty-three patients with refractory solid tumors were treated; 133 courses of FCE 23762 were administered at doses ranging from 30 to 2250 micrograms/m2. The dose limiting toxicity was reversible myelo-suppression (granulocytopenia and thrombocytopenia), demonstrating a delayed nadir and recovery in comparison to doxorubicin. Other toxicities included transient elevation of hepatic transaminases, delayed and prolonged nausea and vomiting, mucositis, anorexia, fatigue, and diarrhea. Heavily pretreated patients demonstrated more myelosuppression than previously untreated patients at 1250 micrograms/m2. No cardiotoxicity was observed. Four objective tumor responses were seen: one complete response in a patient with pelvic recurrence of cervical cancer; one partial response in a patient with cutaneous and lymph gland metastases from head and neck cancer; and two minor responses in patients with liver metastases from colorectal cancer. Plasma concentrations of FCE 23762 and its 13-dihydro metabolite, FCE 26176, were measured in 20 patients at doses > or = 675 micrograms/m2, using HPLC with fluorescence detection. The area under the plasma concentration-time curve ranged from 30 to 80 ng/h/ml; plasma data suggested linear kinetics in the range of tested doses (although there was considerable interpatient variability). The maximum tolerated dose defined in this study using this schedule is 1500 micrograms/m2. A safe phase II dose for previously untreated patients using this schedule is 1250 micrograms/m2; however, this may actually be below the optimal dose for this patient population.
 ...
PMID:Phase I clinical and pharmacokinetic study of 3'-deamino-3'-(2-methoxy-4-morpholinyl)doxorubicin (FCE 23762). 774 8

Twenty patients with primary or metastatic liver cancer were treated on a clinical and pharmacological study with intrahepatic artery infusion of Thiotepa. Toxicity was tolerable and included nausea and fatigue. Uncommon side effects were myelosuppression, abdominal pain and anemia. One patient with gallbladder cancer had a partial response for 11 (+) months. Recommended dose of Thiotepa for future Phase II clinical trials is 1.0 mg/kg. Pharmacokinetics of intrahepatic Thiotepa revealed an extraction ratio similar to that reported for cisplatin. The data suggest increased hepatic clearance for Thiotepa either by binding or metabolism.
 ...
PMID:Clinical and pharmacological study of intrahepatic artery infusion of thiotepa. 781 48

Pyrazine diazohydroxide (NSC-361456) was identified as an active congener of pyridine 2-diazohydroxide with enhanced stability under physiologic conditions. In this phase I study, 35 patients with advanced cancer received 62 courses of PZDH administered intravenously every 3 weeks at doses ranging from 15-608 mg/m2. The dose-limiting toxicity was myelosuppression and the maximal tolerated dose was 487 mg/m2. Hematologic toxicity was delayed and prolonged with median time to recovery about 5 weeks. Mild gastrointestinal toxicity in the form of nausea and vomiting was fairly common. Ondansetron was effective in reducing nausea and vomiting at higher dose levels. Other less common reactions included stomatitis, diarrhea, fatigue, alopecia, and mild abnormalities of renal function and hepatic enzymes. PZDH pharmacokinetics were characterized in 16 patients who received doses of 100-608 mg/m2. Plasma elimination was fit to one (12/16) or two (4/16) compartment model with a mean k10 half-life of 11.5 min. Clearance was dose dependent. Hematologic toxicity was related to PZDH dose, AUC and peak plasma concentration. The sigmoidal relationships between hematologic toxicity and AUC or peak plasma concentration were well described by the Hill equation. There were no objective responses observed in this study. Based on this study, the recommended dose for phase II evaluation of PZDH using this schedule is 390 mg/m2.
 ...
PMID:Pyrazine diazohydroxide (NSC-361456). Phase I clinical and pharmacokinetic studies. 789 39

Taxol (paclitaxel, Bristol-Myers Squibb Company, Princeton, NJ), a drug extracted from the stem bark of the western yew, shows great promise as an antineoplastic agent for ovarian, breast, nonsmall cell lung, and head and neck cancers; melanoma; and leukemia. Although Taxol first was isolated in 1971, completion of many phase I studies was delayed until 1988, primarily because the drug caused severe hypersensitivity reactions. Other side effects of Taxol include cardiotoxicity, nausea and vomiting, diarrhea, mucositis, myelosuppression, tingling and numbness of the hands and feet, myalgia and arthralgia, alopecia, fatigue, headache, irritation at the injection site, and taste changes. Nursing care includes measures for preventing or minimizing side effects, close assessment and monitoring of potential side effects, patient education, and support. Because of the environmental impact of harvesting the western yew for Taxol, semisynthetic preparations such as taxotere are being explored.
 ...
PMID:Taxol: a promising new drug of the '90s. 790 60

Paclitaxel is an antimicrotubule agent that was recently approved by the Food and Drug Administration (FDA). Because it is insoluble in water, it is mixed with Cremophor EL (polyoxyethylated castor oil). The addition of Cremophor requires the use of glass bottles or polyolefin or polypropylene bags and polypropylene-lined tubings for the administration of paclitaxel. In addition, 0.22 micron in-line filters are necessary. The potential side effects of paclitaxel during its infusion include hypersensitivity reaction (HSR), cardiotoxicity, infiltration, diarrhea, and nausea, whereas myelosuppression, neurotoxicity, myalgias, arthralgias, alopecia, fatigue, headache, taste changes, and minor alterations in renal and liver function tests can occur after its administration. Premedications including an H2 blocker, a corticosteroid, and an antihistamine are necessary to minimize the occurrences of HSRs. Vital signs should be monitored throughout the infusion to assess for HSRs and cardiotoxicity. Paclitaxel has been shown to be safe in both the inpatient and outpatient settings. Nursing care includes the administration of the drug, the assessment and management of side effects, and psychosocial support of patients receiving the drug.
 ...
PMID:Nursing implications in the administration of paclitaxel (TAXOL). 790 74


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>