Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a Phase I trial patients with advanced malignant melanoma were treated with high-dose nitrogen mustard (HN2) and autologous bone marrow transplantation. Three patients were entered into the protocol. After procurement of 1.1--5.5 x 10(5) committed stem cells (CFU-C) per kg body wt, 33 mg/m2 of HN2 was administered i.v. as a bolus. Forty-eight hours later the noncryopreserved bone marrow was reinfused i.v. Side effects consisted of nausea, vomiting, anorexia, alopecia, phlebitis, hepatotoxicity, and neurotoxicity. Cardiotoxicity and hypocalcemia were encountered as unanticipated side effects not described so far by using lower dosages of HN2. Granulocytopenia of less than 10 x 10(9)/l and thrombocytopenia of less than 50.0 x 10(9)/l lasted for a mean of 10 and 8 days, respectively. Measureable disease present in two of three patients did not respond to the dose of HN2 used in this protocol. This study shows that hematologic recovery was shorter than previously reported in studies using HN2 without autologous bone marrow transplantation. The nonhematologic side effects of this dose of HN2, however, were severe and preclude the use of higher doses.
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PMID:High-dose nitrogen mustard (HN2) with autologous nonfrozen bone marrow transplantation in advanced malignant melanoma. A phase I trial. 701 56

In summary, procainamide is a useful agent for suppressing premature depolarization frequency. Its short half-life of elimination requires a dosing frequency of every 3 hours with regular dosage forms or every 6-8 hours with a sustained action dosage. Because of the extreme unpredictability of plasma concentration, the dosage must be titrated in each patient with electrocardiographic monitoring serving as the most useful method of evaluating efficacy. Maximum and minimum plasma concentrations are helpful in monitoring the achievement of therapeutic plasma levels and adjusting the frequency of dosing, especially in the presence of impaired renal function or low cardiac output. Adverse effects of procainamide include anorexia, nausea, vomiting, fatigue, insomnia, visual hallucinations, and disorientation; these are minor and cease with discontinuation of the drug. Agranulocytosis has rarely been reported. Long-term treatment has resulted in the occurrence of a lupus-like syndrome that is reversible when the drug is stopped. Procainamide is excreted in breast milk and infants of mothers receiving procainamide should not be nursed.
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PMID:Pharmacokinetics of a sustained release procainamide preparation. 703 27

Carminomycin (CMN) was administered i.v. to 44 patients with a variety of nonhematological cancers every 4 weeks at doses of 15, 20, 22.5, and 25 mg/sq m. Granulocytopenia was the dose-limiting toxicity. The median granulocyte count for previously untreated patients receiving 22.5 mg/sq m was 0.962 cells/microliters, and for previously treated patients receiving 20 mg/sq m it was 0.420 cell/microliters. Moderate to severe phlebitis was associated with drug administration in 50% of cases. Nausea, vomiting, and alopecia were mild. Three of nine patients who received a total CMN dose of greater than or equal to 100 mg/sq m (mean, 132 mg/sq m) developed unexplained decreases in radionuclide cardiac ejection fraction, with one patient developing decreased QRS amplitude and congestive heart failure at a total dose of 160 mg/sq m. CMN is rapidly metabolized to carminomycinol. The elimination half-lives of CMN and carminomycinol are 6 to 10 and 50 hr, respectively. CMN was found to be a more potent inhibitor of human granulocyte-macrophage colony-forming units than was carminomycinol. Objective partial responses were seen in two of seven previously untreated patients with non-small cell lung cancer and one of three patients with squamous cell carcinoma of the head and neck previously untreated with chemotherapy.
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PMID:A phase I and clinical pharmacology study of intravenously administered carminomycin in cancer patients in the United States. 708 81

Since October 1978, 25 patients with metastatic carcinoma of the bladder have been treated with cis-platinum, doxorubicin hydrochloride and cyclophosphamide. Patient selection for this protocol was relatively strict and included only patients who had measurable parameters. All 3 drugs (60 mg./m.2 cis-platinum, 40 mg./m.2 doxorubicin hydrochloride and 400 mg./m.2 cyclophosphamide) were given as a single dose every 4 weeks. Over-all, 19 of the 23 evaluable patients (82 per cent) responded to therapy. There were 5 complete drug-induced remissions and 14 partial remissions. Generally, the treatment was tolerated well and common toxic effects were myelosuppression, nausea, vomiting and alopecia. One patient died of septicemia as a result of agranulocytosis. These promising results seem to indicate the high degree of effectiveness of this combination chemotherapy against transitional cell carcinoma of the bladder.
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PMID:The management of advanced bladder carcinoma. 719 23

To determine whether dimethylsulfoxide (DMSO) can potentiate antitumor activity of cyclophosphamide (CYC) in patients with squamous cell carcinoma of the lung, 14 patients were treated with 5 l of a 5% or 6% DMSO solution PO over 3 days and 1,500 mg CYC/m2 IV as a 60-min infusion on the third day of treatment. Serial blood, CSF, and urine samples were collected to assess the pharmacokinetics of CYC. Courses were repeated every 3-4 weeks. No antitumor responses were observed. Toxicity was mainly hematologic and similar to that of CYC alone. There was one death from infection during granulocytopenia. Nonhematologic toxicity was moderate to severe and included nausea (14 patients) and vomiting (five patients). The plasma pharmacokinetics of CYC in this study are similar to previously reported results for CYC alone, but the 24-h urinary excretion of CYC in our study is much lower than previously reported. Further studies in tumors more responsive to CYC may be warranted.
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PMID:Cyclophosphamide and dimethylsulfoxide in the treatment of squamous carcinoma of the lung. Therapeutic efficacy, toxicity, and pharmacokinetics. 730 30

A phase I trial of the uridine analog 3-deazauridine was undertaken in 44 adults with solid tumors. The drug was given as a 5-day continuous infusion repeated every 3-4 weeks. The dose-limiting toxic effect was granulocytopenia. Patients with prior nitrosourea therapy or extensive irradiation also had significant thrombocytopenia, and the lowest dose tested, 800 mg/m2/day, was excessive for this group. Mucositis was occasionally severe and was particularly marked in previously irradiated areas. Nausea was mild to moderate. There were isolated episodes of rash, headache, chest pain, and blurred vision. For patients without extensive prior therapy, the recommended dose is 1000 mg/m2/day. No complete or partial remissions were noted.
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PMID:Phase I study of 3-deazauridine in the treatment of adults with solid tumors. 747 Nov 19

Twenty-five patients affected with unresectable hepatocellular carcinomas (HCCs) were treated with 370 mg/m2 5-fluorouracil (5-FU) plus 200 mg/m2 racemic leucovorin both for 5 consecutive days. The chemotherapy cycle was repeated every 4 weeks until disease progression. One complete remission (4%) and 6 partial responses (24%) were obtained, that is 7 objective responses in all (28%, ninety-five confidence interval: 10.1-45.9%). All responders had a good PS and only 1 of them presented with bulky disease. Five patients (20%) exhibited stable disease, while the remaining 13 patients (52%) progressed. Toxicity was mild: 11 patients (44%) had grade II/III mucositis, 10 patients (40%) grade II diarrhea, 7 patients (28%) grade II nausea, 2 patients grade III granulocytopenia and 1 patient only (4%) grade I skin toxicity. This regimen made it possible to obtain a high rate of objective responses even in inoperable HCCs which are commonly considered as chemoresistant lesions.
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PMID:5-Fluorouracil and d,l-leucovorin calcium are active to treat unresectable hepatocellular carcinoma patients: preliminary results of a phase II study. 747 36

This study investigated the therapeutic effect of single-agent i.v. weekly Navelbine (vinorelbine), a semisynthetic vinca alkaloid, in women who had received no prior treatment for locally advanced or metastatic breast cancer. Of 68 patients entered into the study, 63 were adequate inclusions, assessable for toxicity and response by WHO criteria; the 5 patients who were not evaluated were excluded from analysis because they were found not to meet the eligibility criteria of the study. Navelbine was given as a weekly 30 mg/m2 short i.v. (20 minutes) infusion; treatment was continued until disease progression. The overall response rate was 44% (complete response 8%, partial response 36%). The response rate according to target was lymph nodes, 62.9%; liver, 50.0%; lung, 50.0%; skin, 37.5%; and primary tumor, 30.8%. The median duration of response was 17.9 weeks (range: 7-52 weeks). The median time to treatment failure was 12.9 weeks, and the median survival was 50.3 weeks. The 63 eligible patients received 501 cycles. The mean dose intensity was 76%. At least one episode of WHO grade 3/4 granulocytopenia was seen in 46% of the patients (13.6% of cycles). Significant nausea/vomiting was seen in only 5% of patients corresponding to 1% of cycles. Only 5% of patients developed WHO grade 3-4 constipation and grade 3 peripheral neuropathy was observed in 1.6% of patients. Alopecia was rare (6.3% of patients), and other side effects were uncommon. This study confirms that Navelbine has major single-agent antitumor activity as frontline therapy in advanced breast cancer. Given its excellent tolerance profile and low morbidity, it should be recommended for inclusion in first-line combination chemotherapy regimens.
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PMID:Phase II trial of weekly i.v. vinorelbine as a single agent in first-line advanced breast cancer chemotherapy. The Latin-American experience. 757 54

This report updates the combined experience of four centres involved in the long-term treatment of transfusional iron overload in 84 patients with the oral iron chelator deferiprone (L1) over 167 patient-years. The source of L1 was variable, including two university research laboratories and three pharmaceutical firms. Compliance was rated as excellent in 48%, intermediate in 36%, and poor in 16% of patients. On a mean L1 dose of 73-81 mg/kg/d, urinary iron excretion was stable, at around 0.5 mg/kg/d, with no indication of a diminishing response with time. Serum ferritin showed a very steady decrease with time from an initial mean +/- 1 SD of 4207 +/- 3118 to 1779 +/- 1154 micrograms/l after 48 months (P < 0.001). 17 patients abandoned L1 therapy. Major complications of L1 requiring permanent discontinuation of treatment included agranulocytosis (three), severe nausea (four), arthritis (two) and persistent liver dysfunction (one). The remaining patients abandoned treatment because of low compliance (three) and conditions unrelated to L1 toxicity (four). Lesser complications permitting continued L1 treatment included transient mild neutropenia (four), zinc deficiency (12), transient increase in liver enzymes (37), moderate nausea (three) and arthropathy (17). There was no treatment-related mortality. Although the complications associated with L1 treatment are significant and require close monitoring, they do not preclude effective long-term therapy in the vast majority of patients. Further well-controlled prospective studies of L1 are required in order to enable proper judgement of its suitability for general long-term clinical use.
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PMID:Results of long-term deferiprone (L1) therapy: a report by the International Study Group on Oral Iron Chelators. 757 38

Estramustine phosphate is a unique antimitotic agent that binds to tubulin and microtubule-associated proteins. Preclinically, estramustine combined with other microtubule inhibitors, like vinblastine or paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), produced additive or greater antimitotic and cytotoxic effects. Clinically, the estramustine/vinblastine combination has significant activity in hormone-refractory prostate cancer. We have begun a phase I study of paclitaxel by 96-hour continuous infusion every 3 weeks combined with daily oral estramustine (600 mg/m2). Eighteen patients with refractory solid tumors have received paclitaxel doses ranging from 80 to 140 mg/m2. Grade 3 or 4 granulocytopenia occurred in one of seven and two of four patients treated at the 120- and 140-mg/m2 dose levels, respectively. The latter two patients experienced grade 3 mucositis and had mean plasma paclitaxel levels exceeding 0.1 mumol/L. Other toxicities, principally nausea and hepatic function abnormalities, have been mild. The apparent steady-state concentrations of paclitaxel 100 and 120 mg/m2 administered with estramustine are similar to those reported for single-agent paclitaxel administered as a 96-hour infusion at doses of 100 and 120 mg/m2. In contrast, at the 140 mg/m2 dose level, paclitaxel concentrations increased throughout the infusion, and steady state was not reached in three of the four patients treated. Objective responses have been observed in two of three patients with adenocarcinoma of the esophagus and in two patients with hormone-resistant prostate cancer and measurable soft tissue metastases. Two additional patients with prostate cancer have been treated with the estramustine/paclitaxel combination, one achieving a major response and the other stable disease. The recommended phase II dose for 96-hour infusional paclitaxel with daily oral estramustine is at least 120 mg/m2. Studies to determine the effect of estramustine on paclitaxel pharmacokinetics are continuing. The antitumor activity observed merits phase II studies of this combination in hormone-resistant prostate cancer and other malignancies.
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PMID:Phase I study of paclitaxel and estramustine: preliminary activity in hormone-refractory prostate cancer. 759 35


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