Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to evaluate the clinical tolerance to multiple IM injections of rDNA-produced human alpha-2 interferon (IFN) (Schering-Plough 30500) in patients with solid tumours. IFN was administered in escalating IM doses in separate groups of patients daily for 14 days and then twice weekly for a further 10 weeks. The dosage levels were 1, 3, 10, and 30 million U/injection. Subjective toxicity could be divided into two types, acute and chronic. The acute reactions took the form of an influenza-like syndrome consisting in chills, rigors, headache, tremor, nausea, vomiting, and myalgia. These symptoms were dose-related but tachyphylaxis developed with continued dosing. The chronic toxicity consisted of malaise, lethargy, fatigue, anorexia, and confusion. These symptoms were not so dose-dependent and tended to become more severe with prolonged treatment. Objective toxicity consisted of myelosuppression and liver dysfunction. Granulocyte counts below 1.0 X 10(9)/l were seen in three patients at the 30-million-U level, with platelet counts less than 100 X 10(9)/l in two of these. Elevation of the liver enzymes were seen in all five patients treated at 30 million U, but returned to normal after 1 week without IFN in all but one patient. A tolerable dose (IM) for phase II/III studies lies between 3 and 10 million U for daily scheduling and between 10 and 30 million U for twice-weekly injections.
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PMID:A phase I toxicity study of human rDNA interferon in patients with solid tumours. 646 93

A phase I study was conducted with dacarbazine (DTIC) protected from light and administered iv as a single dose every 3 weeks. Eighteen patients received 47 courses of DTIC, with doses ranging from 850 to 1980 mg/m2. Hypotension was the dose-limiting toxic effect and it may be secondary to the citric acid present in the pharmaceutic preparation of DTIC. Sporadic myelosuppression was seen at doses greater than 1380 mg/m2. Other side effects noted were nausea and vomiting, acute diarrhea, headache, a "flu-like" syndrome, and a hypersensitivity reaction to sunlight. No antitumor activity was found. The results of this study indicate that this may be a qualitatively different way of giving DTIC, and that the side effects of this drug may be intermingled with those of citric acid in this particular schedule. If the conventional pharmaceutic preparation of this drug is not modified, further studies with high-dose DTIC protected from light should be discouraged.
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PMID:Phase I trial of intermittent high-dose dacarbazine. 670 80

L-Alanosine is an antitumor antibiotic that inhibits adenine synthesis. It showed significant activity in animal tumor systems. Using a daily x 3 dose schedule every 3 weeks, we performed a phase I study to determine toxicity in man. Doses of 8-375 mg/m2/day x 3 were administered to 49 patients in 117 courses. The dose-limiting toxic effect was mucositis. Vomiting, infrequent myelosuppression, fever, headache, malaise, and blood pressure changes were detected at higher dose levels. No antitumor activity was noted. Toxicity with this regimen is acceptable. A phase II study with doses of 250 mg/m2/day x 3 every 3 weeks is feasible.
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PMID:Phase I study of L-alanosine using a daily x 3 schedule. 705 69

The antitumor effect of thymidine has been demonstrated in patients with leukemia and lymphoma. This report summarizes the treatment of three patients with mycosis fungoides, a chronic T-cell lymphoma. Four courses of thymidine (75 g/m2/day) were administered by continuous infusion for 4-7 days. Steady-state serum thymidine levels were in the range of 1-3 mM. Associated toxicities were minimal and consisted of milk headache and anorexia. Myelosuppression was manifested by transient declines in the peripheral leukocyte count. One patient had extensive clearing of diffuse erythematous plaques on the trunk and extremities that persisted for over one month. A second patient had partial clearing of plaques that persisted for two weeks following therapy and a third patient had a minimal response with 25% reduction in lymphadenopathy and noduloulcerative lesions. These responses indicate the effectiveness of thymidine as a single agent in the treatment of mycosis fungoides.
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PMID:Effect of high-dose thymidine infusions in patients with mycosis fungoides. 728 56

High-dose thymidine (dThd) was given to 12 patients with advanced hematological and solid tumors. The dose schedule used was 75 g/sq m/day, given i.v. continuously for 5 days or more. Myelosuppression, especially leukopenia, was the dose-limiting toxicity. Nonhematological toxicities affected the gastrointestinal tract (nausea, vomiting, anorexia, diarrhea, and indigestion) and the central nervous system (somnolence, headache, visual illusions, and memory impairment). Patients who had received cumulative doses of dThd developed alopecia. Thymine crystals were noted in the urine after refrigeration. Tumor regression (less than partial remission) occurred in one patient with melanoma. Three of four patients with acute leukemia had a fall in peripheral white blood cell counts and blasts but no marrow improvement. Four patients with adenocarcinoma (three colon, one unknown primary) had stable disease. Pharmacokinetic studies revealed that, at a dThd dose of 75 g/sq m/day, millimolar concentrations of dThd and thymine can be achieved in the plasma. The half-life of dThd was approximately 100 min. One-third of the plasma concentrations was measurable in the cerebrospinal fluid. dThd was mainly excreted by the kidneys.
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PMID:Clinical phase I-II and pharmacokinetic study of high-dose thymidine given by continuous intravenous infusion. 747 Oct 98

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)
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PMID:Clinical toxicity of the interferons. 751 63

Colony-stimulating factors (CSFs) are glycoprotein growth factors that influence the proliferation and differentiation of hematopoietic progenitor cells. Among CFSs granulocyte colony-stimulating factor (G-CSF) is thought to be major stimulator of production of human neutrophilic granulocyte. G-CSF have recently moved from the basic research to the clinical use and have been suggested to have important roles in cancer management. Today two kinds of recombinant G-CSF which have similar specific activity are commercially available, one is derived from ovarian cells of Chinese hamster and the other from E. coli. (Variant type of E. coli is now in trial.) Difference of these two is whether carbohydrate chain primarily seen in molecule of natural form is contained or not. In this report recombinant product of G-CSF for the clinical use is introduced. Preclinical study with recombinant G-CSF have suggested that it would stimulate granulocyte production in cancer patients with myelosuppression due to chemotherapy. Thus, after evaluation of toxicities and possible efficacy recombinant G-CSF has been introduced into phase II trial for the prevention of chemotherapy-induced neutropenia in various cancers. In this setting 2 micrograms/kg of subcutaneous administration for 14 days after aggressive chemotherapy was suggested to be optimal and to be acceptable for toxicities including bone pain or headache. In conclusion recombinant G-CSF is thought to be very useful drug for reduction of nadir of cancer chemotherapy-induced neutropenia and shortening of period of neutropenia.
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PMID:[Recombinant human granulocyte colony-stimulating factor (G-CSF)]. 768 Aug 49

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.
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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.
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PMID:Nursing implications in the administration of paclitaxel (TAXOL). 790 74

Sixteen patients with intracerebral tumors received intraarterial cisplatin, teniposide, and BCNU combined with intravenous cisplatin, teniposide, and cytosine arabinoside. Oral glycerol and intravenous mannitol were given along with the intravenous chemotherapy in an attempt to increase drug delivery to tumor by augmenting tumor blood flow. Thirteen additional patients were treated with the same regimen, but received all the chemotherapy intravenously. Of the 16 patients receiving intraarterial chemotherapy (median survival, 14 weeks), none responded, 5 (31%) were stable for > 8 weeks, 8 (50%) failed, and 3 (19%) were unevaluable due to early death. Of the 13 patients receiving all their treatment intravenously (median survival, 13 weeks), 3 (23%) responded, 1 (8%) was stable, 7 (54%) failed, and 2 (15%) were unevaluable due to early death. In the patients receiving intraarterial chemotherapy, toxicity included ipsilateral retinal toxicity (2 patients), ocular pain or headache (10), periorbital swelling and flushing (6), increased brain edema with focal neurological deficits and drowsiness (5), and catheter-related carotid artery thrombosis followed by fatal herniation (1). Myelosuppression was worse in patients who received all their treatment intravenously than in those receiving intraarterial chemotherapy (p < 0.05). Neutropenic sepsis developed in 4 patients on the intraarterial arm (1 fatal) and in 5 patients on the intravenous arm (2 fatal). Other toxic effects were similar whether or not patients received intraarterial treatment or only intravenous treatment. Overall, toxicity of this regimen was excessive, and response rates were lower than would have been expected with single agent therapy.
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PMID:Feasibility study of intraarterial vs intravenous cisplatin, BCNU, and teniposide combined with systemic cisplatin, teniposide, cytosine arabinoside, glycerol and mannitol in the treatment of primary and metastatic brain tumors. 812 May 74


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