Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
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Ftorafur is a 5-fluorouracil analogue which is slowly metabolized to 5-FU, resulting in prolonged therapeutic levels of this latter drug. Ninety-one evaluable patients with metastatic breast cancer were treated with Ftorafur, Adriamycin, cyclophosphamide, and BCG (ACFTOR-BCG), in an attempt to increase the effectiveness of the program or decrease its myelosuppressive toxicity. The results of this trial were compared to those previously reported with the combination of 5-FU, Adriamycin, cyclophosphamide, and BCG (FAC-BCG). Overall objective response rates were 65% and 76% for ACFTOR-BCG and FAC-BCG, respectively. Durations of response were 12 months and 14 months for ACFTOR-BCG and FAC-BCG (p = 0.53). The median survival of responders was 22 and 23.9 months, respectively. Substantial toxicity was observed with Ftorafur: nausea and vomiting severe enough to cause weight loss was observed in a substantially higher fraction of the patients treated with this drug than with 5-FU. Other side-effects, which were not observed with the 5-FU combination, were somnolence, dizziness, personality changes, tremor, ataxia, and confusion. No differences in myelosuppressive toxicity were observed between the two combinations, and the incidence of infectious complications was identical. The combination of Ftorafur, Adriamycin, cyclophosphamide and BCG did not offer any advantages with respect to increased effectiveness or reduced toxicity over the FAC-BCG regimen in breast carcinoma.
Cancer 1979 Aug
PMID:Ftorafur, adriamycin, cyclophosphamide and BCG in the treatment of metastatic breast cancer. 38 55

Fifteen patients with advanced gastric cancer were treated with the combination of Ftorafur, Adriamycin and mitomycin-C (FAM II). Three patients showed partial responses, in five the disease remained stable for at least 3 months and seven showed progression while on treatment. All responding patients showed survival in excess of 12 months. Hematologic toxicity was of only moderate severity. Median white count nadir was 3500 cells/mm3 and median platelet nadir was 187,000 cells/mm3. Four patients had white count nadirs from 2000--2500 cells/mm3 and three had nadirs from 500--1500 cells/mm3; also there were four with platelet nadirs less than 100,000/mm3. However, no drug-related infections occurred and no platelet transfusions were required. The major non-hematologic toxicities of the regimen were nausea, vomiting, dizziness, vertigo, and rhinorrhea. These toxicities were limiting and resulted in termination of the trial because of poor patient acceptance and the failure of the combination to exhibit a therapeutic advantage over the similar combination (FAM) that employed weekly 5-fluorouracil in place of Ftorafur.
Cancer 1979 Oct
PMID:A phase II trial of ftorafur: adriamycin and mitomycin-C (FAM II) in advanced gastric adenocarcinoma. 38 3

Nabilone is a cannabinol derivative which has potent central antiemetic effects in animals. We observed that the drug significantly reduced the nausea and vomiting induced by cancer chemotherapy in 10 of 13 patients who were refractory to conventional antiemetics. A dose-response effect was apparent. The drug was generally well-tolerated, although it also had sedative effects. Additionally, dizziness, decreased coordination and postural hypotension were observed in some patients. Euphoric effects of the agent were minimal at antiemetic dosage levels.
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PMID:Nabilone: a potent antiemetic cannabinol with minimal euphoria. 60 7

Seventy patients presenting symptoms of hysteria (49 women and 21 men) were selected among patients observed at the Institute Minkowska during the year. This work is part of a research work on socio-cultural and environmental factors which can change mental status of immigrants. These are all portugese workers presenting for the first time atypical mental troubles called by the author: "bastard hysterical syndrome of the immigrant" and characterized partly or totally by the following symptoms: fatigue, anxiety, sense of suffocation, dyspnea, coughing, unilateral chills or generalized chil, abdominal or gastric pains, headaches and "diffused pains", paresthesia, aching back, tears and sorrow, fear of dying or having a cancer, asthenia, leg paresthesia and contractions, vomiting, diarrhea, cardiac pains, palpitations, dizziness and collapsing. These troubles appear sometimes without apparent motives but they are almost always due to a precipitating cause expressed by the patient: a delivery, a familial death, a homosexual proposition, a trauma without importance, a working conflict etc... But the most frequent cause invoked is "the french climate" without knowing precisely what the word "climate" means: atmospheric conditions, athmosphere or reception milieu? This latest interpretation seems more likely after months of psychotherapy. Most patients are not french speaking and cannot write; their origin is rural (familial villages well structured regarding their food and sexual economy), and people well "armed" by a system of defense mechanisms and well adopted conditioned reflexes. In this work, hysteria of the portugese immigrant is compared to childhood hysteria. As the hysterical burst of the child is aimed at calling attention, love of the mother, at finding a solution to a familial or social conflict, the hysterical burst of the immigrant is aimed at the absent family or at its substitutes, the bos, social security, the doctor. Furthermore, the attitude of the hosting Country--wanting and rejecting--is very ambivalent; "tenderness" at the time of reception, followed by indifference. Early attentions are followed by constant interdictions (threat of unemployment, false statements on sexual dangers of the immigrant etc;..). The immigrant, like the hysterical child, is periodically controlled (work and visit cards), supervised (supervisors), The narcistic satisfactions of being called a good worker can be followed by threats of firing in economic crisis. The society of the hosting country requires the immigrant to be identical to this society: language, physical appearance, food. The real paradoxical situation to which the immigrant is confronted and the real or hypothetical fears constitute conditions of experimental neurosis, to which portugese immigrants react very often by a bastard symptomatology of hysterical type, characteristic of displaced man. These preliminary studies are the frame for a future epidemiological survey in this specific population.
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PMID:[Hysteria and psychosomatic disorders in Portuguese immigrants]. 102 Jun 87

Ftorafur, a furanyl analog of 5-fluorouracil (5-FU), is reported to be five to six times less toxic and possibly more effective in cancer of the breast and colon than 5-FU. The drug was synthesized, formulated, and utilized in toxicologic studies, and then in 24 patients with advanced incurable malignancies. When Ftorafur is given by intravenous push, it results in immediate flushing, dizziness, nausea, retching, and in some cases transient hypotension. These immediate side effects are largely eliminated by administering the drug slowly by infusion. In patients, 60 mg/kg of Ftorafur given i.v. daily for up to 10 days resulted in mild toxicity. However, 80 mg/kg given i.v. daily for 7 days resulted in severe toxicity, with nausea, vomiting, stomatitis, leukopenia, and thrombocytopenia. These studies confirm those of the Russian investigators as to toxicity and dosage, even with a different method of administration more convenient for therapy. Phase II studies are presently being carried out to compare the effectiveness of Ftorafur and 5-FU.
Cancer 1975 Jul
PMID:Phase I study of ftorafur, an analog of 5-fluorouracil. 120 38

Twenty-six patients with relapsed or drug-resistant cancer were treated with a combination of oral etoposide (300 mg day-1 for 3 days) and high-dose oral tamoxifen as a potential modulator of drug resistance (480 or 720 mg day-1 for 6 days beginning 3 days before etoposide). One patient with relapsed high-grade lymphoma and one with adenocarcinoma of unknown primary site has a partial response. Toxicity consisting of nausea, vomiting and subjective dizziness, unsteadiness of gait and malaise occurred during tamoxifen treatment. Serum levels of tamoxifen averaged 3-3.5 microM on day 4 of all courses of treatment at both 480 and 720 mg day-1. N-desmethyltamoxifen levels were lower than tamoxifen during the first course (2 microM) but increased to equal tamoxifen levels during the second course. Didesmethyltamoxifen levels remained below 1 microM. In vitro, both tamoxifen and the standard modulator of multidrug resistance, verapamil, produced minor enhancement of etoposide cytotoxicity in the MCF-7 wt cell line but produced no enhancement with any other cell line. High, intermittent doses of tamoxifen can be given with acceptable toxicity and produce serum levels that have been shown to modulate drug resistance in vitro. In vitro, however, such levels have no significant effect on etoposide cytotoxicity towards a range of wild-type and MDR cell lines.
Br J Cancer 1992 Nov
PMID:High-dose tamoxifen as an enhancer of etoposide cytotoxicity. Clinical effects and in vitro assessment in p-glycoprotein expressing cell lines. 135 68

Toremifene is an antiestrogen that binds strongly to estrogen receptors (ER). A total of 19 previously treated postmenopausal women with metastatic breast cancer whose performance status was good and whose ER status was positive or unknown were studied to determine the maximum tolerated dose of toremifene. Cohorts of patients received 200, 300, or 400 mg/m2 p.o. daily until relapse or unacceptable toxicity had occurred. Nausea, vomiting, and dizziness were dose-related. Three of five patients receiving 400 mg/m2 experienced moderate or severe vomiting and another developed reversible disorientation and hallucinations. Mild sweating, peripheral edema, vaginal discharge, and hot flushes were encountered at all doses. Reversible corneal pigmentation was identified in seven cases but was not of clinical importance. The pharmacokinetics of toremifene was studied weekly and in detail on day 42 using a high-performance liquid chromatographic (HPLC) assay that identified the parent compound and three active metabolites, N-desmethyltoremifene, (deaminohydroxy)toremifene, and didemethyltoremifene. Steady state was achieved at 1-3 weeks. The toremifene area under the curve and the maximal concentration were dose-dependent at high doses. The recommended phase II dose is 300 mg/m2 p.o. daily.
Cancer Chemother Pharmacol 1992
PMID:Phase I clinical and pharmacokinetics study of high-dose toremifene in postmenopausal patients with advanced breast cancer. 138 61

Thirty-eight workers from a factory producing nickel-cadmium and other types of batteries came to us for medical evaluation. They included 21 women and 17 men (seniority 2-20 years, age range 31-63 years), and represented a self-selected subset of 700-900 ever-employed and 200+ recently or currently employed workers in the factory. Thirty-four worked on the nickel-cadmium assembly line. Symptoms and signs included: headache in 34; weakness, fatigue and lassitude in 26; dizziness in 16; pruritus and skin eruptions in 37; gingivitis, teeth loss and caries in 34; nasal congestion, nosebleeds and anosmia in 30; cough, phlegm production, wheezing and shortness of breath in 26; "asthma" in 14; bone pain in 18; urinary frequency, beta 2 microglobulinuria and kidney stones in 17; and sterility or multiple abortions (33) in 8 of 21 women. One additional patient had died from an "amyotrophic lateral sclerosis-like syndrome", while CT scans in six workers revealed brain atrophy. One other worker had leukemia, and two had died from cancer (lung and pancreas). Those who had worked for more than 10 years had more symptoms and signs than shorter-term employees, especially neurological illness, bone pain and urinary tract problems, including beta 2 microglobulinuria. Past blood and urinary cadmium levels were in the range of 1.6-8.7 micrograms/dl and 8-306 micrograms/l, respectively. Our findings indicated that: a) health risks for workers were not confined to the nickel-cadmium assembly line or to older workers, b) hazardous exposures still existed and illness appeared in new workers after a clean-up and intervention program, and c) exposures involved increased risks for renal disease and cancers. Finally, there is a need to control exposures and determine health risks in the full cohort of those ever employed, in the workers' children, and in the surrounding environment (air, ground, water) due to the dumping of waste from the plant.
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PMID:Medical findings in nickel-cadmium battery workers. 142 13

At the beginning, the way intrathecal morphine was used for postoperative pain relief was quite unfortunate, because the doses derived from experience with morphine-tolerant cancer patients were considerably too high and respiratory depression occurred frequently. Subsequent dose-finding studies showed that the doses of morphine used initially could be reduced by a factor of ten without loss of the analgesic effect and with a marked reduction in side-effects. No respiratory depression has been reported when doses below 0.1 mg morphine are used. METHOD. In this prospective study the effect of 0.06 to 0.08 mg intrathecal morphine, mixed with the local anaesthetic for spinal anesthesia, was investigated in surgical patients aged 21 to 81 years, ASA grade I or II, scheduled for orthopaedic operations or herniorraphies. Thirty unpremedicated patients were enrolled in the study and were, after informed consent, randomly allocated to a control group without morphine or to a morphine group. The analgesic effect was assessed by the time interval between the administration of the spinal anaesthesia and the first demand for an analgesic medication. The mood state was evaluated with the adjective checklist of Janke and Debus 6 h after the spinal anaesthesia. RESULTS AND DISCUSSION. In the control group half of the patients asked for an analgesic medication within 275 min (median) after the spinal anaesthesia, and all patients within 420 min, whereas in the morphine group half of the patients asked for an analgesic within 1170 min (median). Seven patients had not required an analgesic at the termination of the observation period 20 h after the spinal anaesthesia. The mood status showed no difference between the two groups, in particular, no dizziness or drowsiness after morphine. There was no difference in the incidence of side-effects such as nausea or urinary retention between the two groups. Pruritus was not reported spontaneously but was found upon questioning in five patients. It was in no case disturbing. CONCLUSIONS. Morphine (0.06 to 0.08 mg) mixed with the local anaesthetic for spinal anaesthesia provided for an analgesia of more than 20 h duration in half of the patients. This technique is safe, simple, reliable and virtually free of side-effects. No particular supervision due to the administration of intrathecal morphine is necessary in this dose range if systemic opiates are avoided. If the analgesia is unsatisfactory, a non-opioid analgesic is recommended.
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PMID:[Intrathecal morphine for postoperative pain]. 146 57

One of a novel series of compounds (AMAPS or arylmethylaminopropanediols), 773U82-HCl has shown significant antitumor activity in in vitro and in in vivo tumor systems, but has less animal CNS toxicity than the lead compound in the same series (crisnatol). This study was designed to evaluate the pharmacokinetics, qualitative and quantitative toxicities of 773U82-HCl and to determine the recommended phase II dose (MTD) of 773U82-HCl given as a short infusion daily for 3 days every 3 weeks. Twenty-nine patients with refractory malignancies received 79 courses over 9 dose levels during this study. Doses ranged from 50 to 1060 mg/m2/d x 3 days. Due to the possibility of local hemolysis with concentrations > 1.5 mg/ml, drug was administered in solutions containing < or = 1.5 mg/ml. Because large volumes were needed at the higher dose levels, the infusion duration was increased from 2 hours to 4 hours. Mild to moderate nausea, vomiting, fatigue, dizziness and headaches were observed. Myelosuppression was the dose limiting toxicity. The recommended phase II dose and schedule was determined to be 800 mg/m2/d x 3d every 3 weeks. 773U82-HCl plasma concentration-time data were analyzed using a two-compartment pharmacokinetic model. The t1/2 beta averaged 6 hours and the total body clearance was 75.9 L/hr/m2. The volume of distribution (Vdss) was large, averaging 470 L/m2.
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PMID:Phase I evaluation of 773U82-HCl in a two-hour infusion repeated daily for three days. 148 1


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