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)

Paclitaxel is a novel antineoplastic that effects cytotoxicity by promoting intracellular tubulin polymerization and stabilizes abnormal microtubule structures against depolymerization. Although its clinical development had been hampered by misconceptions about its pharmacology, its scarcity, difficulties extracting it from its natural source, formulation problems, and frequent severe hypersensitivity reactions, paclitaxel recently was approved for treatment-refractory ovarian cancer. Two major adverse effects are dosage- and schedule-related myelosuppression and mucositis. Neurotoxicity is directly related to both the individual and cumulative doses. Other relevant toxicities are hypersensitivity reactions, effects on cardiac rate and rhythm, arthralgias and myalgias, generalized hair loss, and mild nausea and emesis. Continuing clinical studies will evaluate paclitaxel as initial therapy for ovarian cancer and its utility in other malignancies. In addition, major efforts are under way to develop alternative sources to increase the availability of taxene analogs and reduce our dependence on yew species.
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PMID:Paclitaxel (taxol). 790 50

The relation between pretreatment night-time urinary catecholamine excretion and chemotherapy-induced nausea and vomiting was studied. The first cohort included 17 women and three men with various cancer forms receiving low or moderately emetogenic chemotherapy. The second cohort included 42 women receiving cisplatinum (50 mg m-2) for ovarian cancer and ondansetron as an antiemetic (8 mg i.v. x 3 at chemotherapy and 8 mg p.o. x 3 for 5 days). Relatively higher noradrenaline, but not adrenaline, excretion was associated with an increased intensity of delayed nausea following treatment. Vomiting was not consistently related to the excretion of either catecholamine. The results indicate that noradrenaline modulates delayed nausea resulting from chemotherapy.
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PMID:Delayed chemotherapy-induced nausea is augmented by high levels of endogenous noradrenaline. 759 61

We conducted a multicenter Phase II study of BMS-181339 in patients with ovarian cancer. The facilities participating were 23 in number. The total number of cases registered for the study were 62; 57 of them entered for evaluation in drug efficacy, and 58 cases were evaluable in drug safety. All the cases were previously treated with chemotherapy including platinum-based drugs. The clinical responses of BMS-181339 were as follows: CR, 1 case; PR, 13 cases; MR, 3 cases; NC, 13 cases and PD, 27 cases. The response rate was 24.6% (95% CI: 14.1-37.8%). Histologically, the drug showed its efficacy on serous adenocarcinoma 28.2% (11/39), mucinous adenocarcinoma 20.0% (1/5) and clear cell adenocarcinoma 20.0% (1/5). In regional evaluation, the drug demonstrated its efficacy not only on endopelvic lesions 19.0% (4/21) and abdominal lesions 14.3% (2/14), but also on remote metastatic lesions such as hepatic metastasis 30.8% (4/13) and lung/pleura 33.3% (2/6). The drug also showed its efficacy on the cases 22.9% (8/35) refractory to the platinum-based drugs. Major adverse reactions were fever 63.8% (37/58), alopecia 59.3% (32/54), peripheral nerve disorders 28.1% (16/57) such as numbness of the extremities, nausea/vomiting 24.1% (14/58), arthralgia 20.7% (12/58) and diarrhea 20.7% (12/58) etc.. Abnormal alterations in laboratory test values were an incidence rates of 100% for both leukopenia and neutropenia. However, these symptoms were clinically manageable by transient withdrawal of medication, dose reduction and administration of antibiotics and G-CSF. In addition, decrease in hemoglobin 93.1% (54/58), decrease in platelet counts 31.0% (18/58), elevation in GOT 27.6% (16/58), in GPT 31.0% (18/58) and in LDH 20.7% (12/58) were seen, but no serious organopathy was observed. Thus, we confirmed that BMS-181339 was a clinically useful chemotherapeutic agent in patients with ovarian cancer.
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PMID:[A phase II study of BMS-181339 in patients with ovarian cancer. BMS-181339 Ovarian Cancer Study Group]. 794 92

In view of the single agent activity of both cisplatin and carboplatin in epithelial ovarian cancer, and their different toxicity profiles, we carried out a phase II study of low dose cisplatin (50 mg/m2) in combination with moderate dose carboplatin (300 mg/m2) in patients with advanced ovarian cancer. Fourteen patients, all of whom had bulky disease and over half of whom had Stage IV disease, were eligible for assessment of response and toxicity. An overall response rate of 71% was demonstrated (57% complete response, 14% partial response), which is at least equivalent to other regimens used in first line treatment of ovarian cancer. Toxicities encountered were nausea/vomiting and myelosuppression, however no serious renal neuro or ototoxicity was observed and the regimen does not cause significant alopecia. This combination may be a practical alternative to regimens which use high dose cisplatin to achieve similar efficacy.
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PMID:A phase II study of carboplatin and cisplatin in advanced ovarian cancer. 795 35

The purpose of this work was to determine the maximum tolerated (phase II) dose of melphalan and etoposide that can be given in conjunction with autologous BM re-infusion in patients who have refractory or relapsed solid tumors. Twenty-six patients with refractory or relapsed breast cancer (n = 15), small cell lung cancer (n = 1), ovarian cancer (n = 3), colorectal cancer (n = 3) or malignant melanoma (n = 4) were enrolled and treated in this phase I study. Patients ranged in age from 31 to 60 years (median 44.5 years). Melphalan 180 mg/m2 (60 mg/m2/day for 3 consecutive days i.v. over 30 min) and etoposide 1200-3600 mg/m2 (400-1200 mg/m2/day for 3 consecutive days i.v. over 4 h) were given followed by autologous BM infusion 60-72 h after completion of chemotherapy. Ten patients received GM-CSF or G-CSF therapy after marrow re-infusion. Regimen-related toxicities included fever, pancytopenia, mucositis, nausea, vomiting, diarrhea, esophagitis, hepatic dysfunction and infection. Neutrophils recovered to > 500 x 10(6)/l and platelets recovered to > 20 x 10(9)/l (without transfusions) a median of 17 days and 20.5 days after marrow infusion, respectively. Dose-limiting toxicity occurred at an etoposide dose of 3600 mg/m2, since 4 of 6 patients treated at this dose level experienced grade 4 NCI Common Toxicity Criteria (mucositis (n = 3) and infection (n = 1)). Complete responses were noted in 7 patients (breast cancer (n = 5), colorectal cancer (n = 1) and melanoma (n = 1)); partial responses were observed in 5 patients. Melphalan 180 mg/m2 and etoposide 3000 mg/m2 is a potent high-dose chemotherapy regimen with significant antineoplastic activity, particularly for breast cancer, and has acceptable toxicity when administered in conjunction with autologous BM re-infusion.
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PMID:Phase I trial of high-dose melphalan, high-dose etoposide and autologous bone marrow re-infusion in solid tumors: an Eastern Cooperative Oncology Group (ECOG) study. 799 70

Female patients with ovarian cancer are at high risk for emesis. A study evaluating the antiemetic activity and tolerability of ondansetron plus dexamethasone compared to metoclopramide plus dexamethasone plus diphenhydramine in this group of patients has been performed. A group of 63 patients with ovarian cancer undergoing cisplatin treatment were enrolled in the study. Vomiting, nausea and other side-effects were evaluated by the investigators during the first 24 h and recorded by the patients on a diary card on days 2-4. Ondansetron plus dexamethasone showed a higher antiemetic activity during the first 24 h after cisplatin administration in all three cycles of cisplatin treatment, giving over 90% complete protection from vomiting at the first cycle. The efficacy of ondansetron plus dexamethasone decreased at the second cycle, but the percentage of complete protection from vomiting always remained better than 70%; there was poorer protection in the metoclopramide group, and its effect was similar during all three cycles. Ondansetron plus dexamethasone was also found to be more efficacious than the metoclopramide regimen on the second day after cisplatin administration, while on days 3-4 a high rate of complete protection from emesis was achieved by both antiemetic therapies (> 80%). About 40%-55% of patients receiving ondansetron plus dexamethasone and about 65%-85% of patients treated with metoclopramide plus dexamethasone plus diphenhydramine reported nausea or vomiting during days 1-4. Ondansetron plus dexamethasone is more efficacious than metoclopramide plus dexamethasone plus diphenhydramine but new strategies to improve antiemetic efficacy in ovarian cancer patients must be outlined.
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PMID:Ondansetron plus dexamethasone versus metoclopramide plus dexamethasone plus diphenhydramine in cisplatin-treated patients with ovarian cancer. Italian Group for Antiemetic Research. 803 96

The occurring frequency of 14 most common chemotherapy and anti-nausea drug side-effects was examined. The studies were performed on 29 women with ovarian cancer treated by total number of 125 chemotherapy courses (schedule PAC and Acy) and additionally, in order to eliminate nausea caused by the chemotherapy, by anti-nausea drugs (Zofran, Solu-Medrol, Droperidol, Metoclopramide + Fenactil, Torecan). Zofran caused the fewest number of side-effects, solu-medrol inhibited nausea and vomiting significantly, however it caused many side-effects such as flush on a face, restlessness, incitement and headaches. Torecan did not prevent patients from vomiting. The greatest number of side-effects was observed after droperidol and metoclopramide + fenactil treatment.
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PMID:[Side effects of drug treatment for ovarian cancer after administration of antiemetic drugs]. 814 54

Cisplatin combined with cyclophosphamide has been considered a very active treatment for advanced ovarian cancer. Unfortunately, cisplatin is associated with dose-limiting neurotoxicity, as well as possible neuropathy, ototoxicity, and occasional renal dysfunction. Carboplatin, a cisplatin analogue, is active against advanced ovarian cancer, with a presumed lower incidence of emesis, ototoxicity, neuropathy, and renal dysfunction. The Southwest Oncology Group initiated a phase III randomized trial, in which 342 patients with stage III (suboptimal disease) and stage IV ovarian cancer were randomly assigned to treatment with six courses of intravenous cisplatin 100 mg/m2 plus cyclophosphamide 600 mg/m2 or carboplatin 300 mg/m2 plus cyclophosphamide 600 mg/m2. The median survival for the cisplatin arm was 17.4 months; for the carboplatin arm, median survival was 20.0 months. The null hypothesis of a 30% survival superiority with the cisplatin arm was rejected at the p = 0.02 level. Clinical response rates were 52% for the cisplatin arm and 61% for the carboplatin arm. There was less thrombocytopenia in the cisplatin arm (p < 0.001); however, there was less nausea and emesis (p < 0.001 for courses one to five), renal toxicity (p < 0.001), anemia (p < 0.001), hearing loss (p < 0.001), and neuromuscular toxicity (p < 0.001) in the carboplatin arm. Carboplatin/cyclophosphamide proved to have a significantly better therapeutic index than cisplatin/cyclophosphamide in these patients with advanced ovarian cancer.
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PMID:Results of a Southwest Oncology Group phase III trial of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide in advanced ovarian cancer. 823 97

New cisplatinum derivatives of 254-S, DWA2114R and NK121 developed in Japan were reviewed. These three compounds have less nephrotoxicity and nausea/vomiting than cisplatinum, but have more myelotoxicity. 254-S showed activities against carcinomas of the head and neck, lung, esophagus, urinary tract, prostate, testis, ovary and cervix. DWA2114R showed activities against carcinoma of the ovary, prostate, testis and breast. NK121 is under phase II study. A randomized controlled study of 254-S for non-small-cell lung cancer and DWA2114R for ovarian cancer was performed compared to cisplatinum. The antitumor activity of these compounds was not different from cisplatinum, however the hydration was much less than cisplatinum. These cisplatinum derivatives of 254-S and DWA2114R were thought to be useful for QOL of the patients treated with cisplatinum compound.
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PMID:[Cisplatinum compounds]. 838 Jun 87

Twenty-two patients with ovarian cancer stage III and IV received combination chemotherapy with CDDP, adriamycin (ADM) and cyclophosphamide (CPM), and were studied for response and side-effects. Patients were divided into two groups according to the following CDDP infusion schedules. (CAP 1) CDDP 7mg/sqm/8 hrs/saline 500 ml/d1-d10, ADM 35 mg/sqm/d1, CPM 350 mg/sqm/d1: 8 cases; (CAP 2) CDDP 70 mg/sqm/2 hrs/d1, ADM 35 mg/sqm/d1, CPM 350 mg/sqm/d1: 14 cases. The overall response rate (CR + PR) was 62.5% in CAP 1, and 50% in CAP 2 (on statistical difference: NS). The 3-year survival rate was 54.7% in CAP 1 and 38.5% in CAP 2 (NS). Side effects of nausea, vomiting and nephrotoxicities were remarkably reduced in CAP 1. These data suggest that lower concentration and longer infusion time of CDDP administration increases the therapeutic index. This infusion schedule is suitable for chemotherapy at home or on an outpatient clinic basis, especially in patients with ovarian cancer.
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PMID:[Increase in CDDP therapeutic index by lower concentration and longer infusion time--home chemotherapy for ovarian cancer]. 843 65


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