Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Midazolam (RO 21-3981), a water soluble benzodiazepine, was used in combination with fentanyl as a total intravenous anaesthetic for outpatient cystoscopy. It was compared with a similar technique using Althesin and fentanyl. In both series good conditions were produced, and patient acceptance was high, with absence of pain on injection, no inappropriate muscle movements and no nausea or vomiting. The induction and recovery times were slightly longer in the midazolam series, but not undesirably so. There appeared to be a slight incidence of phlebitis with midazolam, but because the patients were discharged from hospital, the exact incidence could not be ascertained with certainty.
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PMID:Midazolam/fentanyl. A total intravenous technique for short procedures. 710 24

Thirty-four patients were treated with N-(phosphonacetyl)-L-aspartate (PALA) at a dose of 850 mg/m2/day x 5 by continuous intravenous infusion (days 1-5) and 5-fluorouracil (5-FU) on an escalating dose schedule of 300-630 mg/m2/day x 5 by continuous intravenous infusion (days 2-6). Dose-limiting oral mucositis occurred at a 5-FU dose of 560 mg/m2/day; other toxicities included nausea, vomiting, diarrhea, skin rash, and superficial venous phlebitis. Myelosuppression was rare. One partial response was observed in a patient with metastatic colorectal carcinoma. Plasma PALA levels were monitored in seven patients. Steady-state levels were achieved by the 2nd day of drug infusion and ranged between 10 and 20 micrograms/ml.
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PMID:A phase I trial of combination therapy with continuous-infusion PALA and continuous-infusion 5-FU. 712 61

The efficacy of intravenously administered prostaglandin E2 (PGE2) compared to that of intravenously administered 16-phenoxy-17,18,19,20 tetranor prostaglandin E2 methyl sulfonylamide (SHB 286) for termination of fetal death in utero was evaluated in 20 pregnant women from 14 to 38 weeks' gestation. Ten subjects received 1 microgram of PGE2 per minute intravenously. This rate of infusion was doubled at hourly intervals up to 8 microgram per minute. Ten subjects received 0.25 microgram of SHB 286 per minute. This rate of infusion was doubled at hourly intervals up to 2 microgram per minute. It appears that the dosage schedules of PGE2 and SHB 286 were equally effective in inducing labor. Cumulative expulsion rates and mean induction times were similar in both groups. Rates of emesis were low in both groups. Either fever greater than 38.0 degrees C, or shivering, or phlebitis at the site of infusion was observed in three patients treated with PGE2 but in no patient receiving SHB 286.
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PMID:Intravenous prostaglandin E2 and 16-phenoxy prostaglandin E2 methyl sulfonylamide for induction of fetal death in utero. 736 92

Coupling of anthracyclines to high-molecular-weight carriers may alter drug disposition and improve antitumor effects. We have performed a clinical phase I trial of doxorubicin coupled to dextran (70000 m.w.). The drug was administered as single dose i.v. every 21-28 days. Thirteen patients have received a total of 24 courses (median 2; range 1-3). At the starting dose of 40 mg/m2 doxorubicin equivalent (DOXeq), WHO grade IV thrombocytopenia was noted in 2/2 patients. WHO grade IV hepatotoxicity and WHO grade III cardiotoxicity were noted in a patient with preexisting heart disease. Five patients were treated with 12.5 mg/m2 DOXeq. Maximal toxicity at this dose level was WHO grade III thrombocytopenia and local phlebitis (WHO grade II) in 1/5 patients, elevation of alkaline phosphatase (WHO grade III) and WHO grade III vomiting in another patient. Subsequently, five patients received 20 mg/m2 DOXeq. Hepatotoxicity was noted in 5/5 patients (1 x WHO grade IV, 1 x WHO grade III). Thrombocytopenia was noted in 3/5 patients (1 x WHO grade IV, 2 x WHO grade III). At 12.5 mg/m2 DOXeq, a patient diagnosed with a malignant fibrous histiocytoma had stable disease for 4 months. Pharmacokinetic analyses of total and free doxorubicin were performed in plasma and urine. The maximum peak plasma concentration (ppc) for total DOX was 12.3 micrograms/ml at 40 mg/m2 DOXeq. The area under the plasma concentration time curve (AUC) ranged from 28.83-80.21 micrograms/ml*h with dose-dependent elimination half lives (t1/2 alpha: 0.02-0.87 h; t1/2 beta: 2.69-11.58 h; t1/2 gamma: 41.44-136.58 h).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase I clinical and pharmacokinetic trial of dextran conjugated doxorubicin (AD-70, DOX-OXD). 750 68

A third-generation platinum analogue, zeniplatin, was administered at a dose of 145 mg/m2 intravenously over 60-90 minutes every 21 days as the initial chemotherapy to 21 patients with metastatic melanoma. Prehydration and mannitol diuresis was introduced after the first 7 patients. There were 17 males and 4 females. The median age was 52 (range: 29-81). ECOG performance status was 0 in 10 patients, 1 in 8 patients and 2 in 3 patients. Major disease sites were lymph nodes, skin, lung, liver, and bone. Patients received a median of 2 cycles (range: 1-7). Two patients achieved partial responses. One with nodal disease progressed after 166 days and the other with buccal mucosal disease after 142 days. A third patient showed partial regression of nodal disease but developed cerebral metastases. Gastrointestinal toxicity included WHO grade 3 vomiting in 8 patients and nausea in 2. Antiemetics were used, but ondansetron was not available. WHO grade 3 hematologic toxicities included neutropenia in 8 patients and anemia and thrombocytopenia in 1 patient. Thrombocytosis was seen in 35% of courses. Dosage reduction was required in 15% of courses and escalation in 5% of courses. Three patients developed phlebitis related to the infusion. One patient developed a reversible rise in serum creatinine, but, unlike other studies, no severe nephrotoxicity was reported. Zeniplatin demonstrated only modest activity in melanoma with significant gastrointestinal and hematologic toxicity.
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PMID:A phase II trial of zeniplatin in metastatic melanoma. 784 60

Thirty consecutive patients with stage IIIB-IV non small cell lung cancer were treated with a combination of cisplatin 80 mg/m2 on day 1 plus vinorelbine 25-30 mg/m2 on days 1, 8. This cycle was repeated every 3 weeks. The overall response rate was 46%, with 1 patient showing a complete response and 13 patients (43%) a partial response with a mean duration of 8.4+ months. Six patients had a stabilization and 10 progressed. The main toxicities were represented by myelosuppression and nausea/vomiting. Grade 3 leukopenia was seen in 33% of cases, grade 2 thrombocytopenia in 12%, and phlebitis in the injection vein in 16%. Mild constipation was also recorded. The combination of cisplatin plus vinorelbine is quite effective in advanced non small cell carcinoma of the lung, and may be safely given on an outpatient basis.
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PMID:Vinorelbine plus cisplatinum for the treatment of stage IIIB and IV non small cell lung carcinoma. 806 91

N-Debenzoyl-N-tert-butoxycarbonyl-10-deacytyl taxol (Taxotere, RP 56976) is a semisynthetic analogue of taxol, prepared from a noncytotoxic precursor extracted from the needles of the European yew tree (Taxus baccata L.). It has a broad spectrum of antitumor activity against a variety of transplantable tumors in mice. In vitro cytotoxicity assays suggest that it is 2-5-fold more potent than taxol. In this phase I study Taxotere was administered by 24 h i.v. infusion at 3-week intervals. Thirty patients with solid tumors refractory to conventional therapy were treated; 70 courses of Taxotere were administered at doses ranging from 10 to 90 mg/m2. Grade 4 neutropenia and grade 3 mucositis were dose limiting but reversible at 90 mg/m2. The pattern and grade of toxicity at this dose were similar in 3 heavily pretreated patients compared with 7 patients who had received a maximum of one previous chemotherapy regimen. Alopecia occurred at 55 mg/m2 and above. Other mild toxicities included phlebitis, diarrhea, emesis, and sensory peripheral neuropathy, but these were neither dose-limiting nor clearly dose-related. One patient treated at 70 mg/m2 had an anaphylactoid reaction following the second dose of Taxotere. No cardiovascular toxicity was observed. No partial or complete responses were documented. Plasma concentrations of Taxotere were determined by high-performance liquid chromatography, and end-of-fusion levels at the maximum tolerated dose exceeded drug concentrations which are cytotoxic in vitro. The maximum tolerated dose for Taxotere administered as a 24-h infusion is 90 mg/m2.
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PMID:Phase I and pharmacokinetic study of taxotere (RP 56976) administered as a 24-hour infusion. 809 54

A multi-institutional early phase II study of KW-2307 (vinorelbine), a new vinca alkaloid derivative, in advanced or recurrent breast cancer was conducted in 15 nationwide hospitals. KW-2307 was intravenously administered once weekly at doses of 15 to 25 mg/m2. Sixty-five among the enrolled 69 patients were eligible. Response rates were 11.8% (2/17) with 15 mg/m2, 28.0% (7/25) with 20 mg/m2 and 17.4% (4/23) with 25 mg/m2, and the overall response rate was 20.0%. Once-weekly intravenous administration of 20 mg/m2 was estimated to be the optimal dose of KW-2307 from the results. The major side effect was leucopenia, which was the dose-limiting factor in this study. Other subjective or objective side effects included anorexia, nausea-vomiting, phlebitis, fever, general fatigue and stomatitis, but none of them was serious.
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PMID:[Early phase II study of KW-2307 in advanced or recurrent breast cancer. KW-2307 Cooperative Study Group (Breast Cancer Section]. 818 37

A multicenter early Phase II clinical study of KW-2307, a new vinca alkaloid derivative, in patients (pts) with lung cancer was conducted in 15 hospitals. Ninety-seven pts were enrolled, among whom 95 were eligible. Seventy of the eligible pts had non-small cell cancer (NSCLC) and 25 had small cell cancer (SCLC). PR was obtained in 13 (18.6%) of NSCLC pts and 3 (12%) of SCLC pts. Only those who had no previous chemotherapy showed PR in NSCLC pts, and the response rate in these pts was 29.5% (13/44). As to the correlation between dosage and tumor effect, a better effect was exhibited at higher doses, with response rates of 21.7% (5/23) and 38.1% (8/21) at 20 mg/m2 and 25 mg/m2, respectively. The major adverse effect of this drug was leukopenia (neutropenia), which was Grade 3 or 4 in many cases. Recovery from this complication, however, was rapid. Other adverse effects included mild hepatic dysfunction, anorexia, nausea/vomiting, fever, general fatigue, phlebitis and constipation. The incidence of peripheral nervous disorder such as the paresthesia commonly observed with vinca alkaloids, was as low as 10%, and the symptoms, if any, were mild.
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PMID:[Early phase II clinical study of KW-2307 in patients with lung cancer. Lung Cancer Section in KW-2307 Study Group]. 818 36


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