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)

We have conducted a phase I clinical trial of maytansine, a plant alkaloid with potent tubulin-binding activity. For evaluation of toxicity, the schedule of drug administration consisted of a single iv infusion given every 3 weeks. Dose-limiting toxicity was observed at 2 mg/m2, and was manifested as profound weakness, diarrhea, nausea, and vomiting. Symptoms persisted for 3--14 days after drug administration. No consistent myelosuppression occurred at any dose level. Responses were observed in two patients (one each with non-Hodgkin's lymphoma and ovarian cancer) who were treated on the every-3-week schedule, as well as in two patients with acute lymphocytic leukemia treated with single weekly doses. Three of the four responding patients had received extensive prior treatment with vincristine, and two were clearly resistant to vincristine.
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PMID:Initial clinical trials of maytansine, an antitumor plant alkaloid. 34 11

The preliminary results of Cycloplatin in non small cell lung cancer were presented. Cycloplatin is a new derivative of Cisplatin but less nephrotoxic. Its. referring preparation is Carboplatin 14% remissions were found in the cases of inoperable non small cell lung cancer and 12% remissions in advanced ovarian cancer. 84% of patients suffered from vomiting what was the most common reported side-effect.
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PMID:[Studies of the clinical use of cycloplatin--a new derivative of cisplatin]. 133 30

A pharmacological, behavioural and nursing intervention strategy was evaluated for prevention of cisplatin (50 mg m-2) induced emesis in ovarian cancer patients. 46 patients received metoclopramide 2.5 mg kg-1 i.v., b.i.d., dexamethasone 20 mg i.v., lorazepam and biperiden as well as training in relaxation, nutritional advice and continuity in nursing care. Controls (n = 34) received standard treatment (metoclopramide 10-20 mg i.v. or dixyracin 20 mg i.v.). The intensity and duration of nausea and vomiting were significantly lower and measures of quality of life higher for patients on the experimental ward during the three cycles that were studied. No significant changes in emesis were observed between the cycles. There was no correlation between emesis and any of the parameters of quality of life measured. The reliability and validity of nausea ratings are discussed and we suggest that an underreporting of nausea and vomiting might be common.
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PMID:Control of cisplatin induced emesis--a multidisciplinary intervention strategy. 134 20

Cisplatin is generally accepted to be the most active cytotoxic agent for the treatment of ovarian cancer but the optimum dose remains unclear. We have performed a randomised trial to assess the importance of cisplatin dose in the treatment of advanced epithelial ovarian cancer. Patients were randomly assigned treatment with 50 mg/m2 (low dose) or 100 mg/m2 (high dose) cisplatin plus 750 mg/m2 cyclophosphamide, for a maximum of six cycles with intervals of 3 weeks. We planned to recruit 300 patients, but an interim analysis on the first 165 indicated a highly significant survival difference (p = 0.0008). Recruitment was therefore stopped and the trial patients were followed-up for 12 months longer. The relative progression rate (high-dose/low-dose) after 12 months' extra follow-up was 0.55 (95% confidence interval 0.37-0.81, p = 0.003) and the relative death rate 0.53 (0.34-0.81, p = 0.003). Overall median survival was 69 weeks in the low-dose group and 114 weeks in the high-dose group. Residual disease extent before chemotherapy had an important influence--patients with lesions of less than 2 cm did best; if given high-dose cisplatin their median survival was 3 years. 56 low-dose and 45 high-dose patients completed six cycles of chemotherapy; 15 and 9 patients, respectively, were withdrawn early because of progressive disease and treatment was stopped in 6 and 25, respectively, because of unacceptable side-effects or patient refusal. Toxic effects were significantly greater in the high-dose group, especially those on the nervous system and ears, alopecia, vomiting, and anaemia. Although the higher dose of cisplatin clearly leads to better results in terms of survival, its overall clinical benefit in the management of ovarian cancer will depend on further improvements in measures to alleviate toxic effects.
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PMID:Randomised study of two doses of cisplatin with cyclophosphamide in epithelial ovarian cancer. 135 47

The patients with ovarian cancer are apt to combine peritonitis carcinomatosa (PC). The effect of intraperitoneal (IP) administration of CDDP against peritonitis carcinomatosa was examined. Hydration was not necessary when CBDCA was injected, because nephrotoxicity of CBDCA was very low compared to CDDP. We studied pharmacokinetics of IP-CBCCA and its efficacy and safety. Four hundreds and fifty mg of CBDCA was dissolved in 1,000 ml of saline and administrated through the subcutaneously implanted Infuse-A-Port for 60 minutes. Complete response was 25%. The platinum concentration in the ascites (injected saline) decreased to 90.8 micrograms/ml at 2 hr after administration and to 3.8 micrograms/ml at 24 hrs, and 79.7 97.5% existed as free Pt. The concentration of serous Pt reached to 6.2 micrograms/ml at 15 min. and was kept at 6-8 micrograms/ml. and 52.4-92.7% existed as free Pt in serum. Pt was excreted to urine and reached to the peak concentration at 4 hr. Adverse effect was mainly myelotoxicity without renal toxicity and emesis. Leukocytopenia of grade 4 was 14.3%, thrombocytopenia was 25.0%. We tried IP administration to the outpatients. The doses were mainly 300 mg, but in some cases, it was escalated to 450 mg, Adverse effect of 300 mg was thrombocytopenia of grade 4 (4.8%). These results suggest that IP administration of CBDCA seemed to be a new method as locosystemic chemotherapy. We demonstrated new chemotherapeutic method to outpatients.
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PMID:[Pharmacokinetics of carboplatin after intraperitoneal administration and clinical effect in ovarian cancer]. 146 42

A phase II trial of single-agent carboplatin in advanced ovarian cancer was performed by 19 institutions from 10 European countries. A total of 260 patients were treated, with a median age of 55 (range: 20-79) years. Karnofsky performance status was 80-100 in about two-thirds of the patients. Prior therapy consisted of surgery only in 31 patients, irradiation in 9, chemotherapy without cisplatin in 45, and with cisplatin in 175. Carboplatin was administered as second-line therapy in about one-half and as third-line or more in one additional third of the study population. Initial dose was 400 mg/m2 in 90, 360 mg/m2 in 152, and 320 mg/m2 or less in 18 patients. A total of 971 courses (mean 3.7, median 2, range: 1-13) of therapy were administered. A total of 16 complete and 46 partial responses were observed in 226 evaluable patients, for an objective response rate of 27%. Efficacy was greater in chemotherapy-untreated patients (51% vs. 23%, p = 0.002). In cisplatin-pretreated patients activity was significantly higher in non-refractory patients (26% vs. 4%, p = 0.015). Myelosuppression was the most significant side effect. However, low hematologic counts seldom translated into clinically significant complications. Patients with impaired baseline creatinine clearance and poor performance status were at higher risk of developing severe myelosuppression during the initial course of treatment. Non hematologic side effects were rare and mild, except for emesis. Carboplatin has a definite role in the treatment of ovarian cancer, but almost complete cross-resistance with the parent compound was observed clinically.
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PMID:A multicenter phase II study of carboplatin in advanced ovarian carcinoma: final report. 158 19

The efficiency of cis Platin (DDP) alone and in combination with Adriamycine (ADM) and Cyclophosphamid (CTX) were evaluated in a prospective randomized trial containing 173 pat. suffering from advanced ovarian cancer (FIGO III/IV). Therapeutic schedule and results: (table; see text) The most side effects concerned vomiting (WHO Grad 2) in 90%, nausea (WHO Grad 2) in 95% and alopecia in 50% out of all pat.
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PMID:[Effectiveness of cisplatin alone and in combination within the scope of primary therapy of ovarian cancer. Results of a prospective multicenter study]. 169 49

Ifosfamide is an oxazaphosphorine alkylating agent with a broad spectrum of antineoplastic activity. It is a prodrug metabolised in the liver by cytochrome P450 mixed-function oxidase enzymes to isofosforamide mustard, the active alkylating compound. Mesna, a uroprotective thiol agent, is routinely administered concomitantly with ifosfamide, and has almost eliminated ifosfamide-induced haemorrhagic cystitis and has reduced nephron toxicity. Therapeutic studies, mostly noncomparative in nature, have demonstrated the efficacy of ifosfamide/mesna alone, or more commonly as a component of combination regimens, in a variety of cancers. In patients with relapsed or refractory disseminated nonseminomatous testicular cancer, a salvage regimen of ifosfamide/mesna, cisplatin and either etoposide or vinblastine produced complete response in approximately one-quarter of patients. As a component of both induction and salvage chemotherapeutic regimens, ifosfamide/mesna has produced favourable response rates in small cell lung cancer, paediatric solid tumours, non-Hodgkin's and Hodgkin's lymphoma, and ovarian cancer. Induction therapy with ifosfamide/mesna-containing chemotherapeutic regimens has been encouraging in non-small cell lung cancer, adult soft-tissue sarcomas, and as neoadjuvant therapy in advanced cervical cancer. As salvage therapy, ifosfamide/mesna-containing combinations have a palliative role in advanced breast cancer and advanced cervical cancer. Ifosfamide/mesna can elicit responses in patients refractory to numerous other antineoplastic drugs, including cyclophosphamide. With administration of concomitant mesna to protect against ifosfamide-induced urotoxicity, the principal dose-limiting toxicity of ifosfamide is myelosuppression; leucopenia is generally more severe than thrombocytopenia. Reversible CNS adverse effects ranging from mild somnolence and confusion to severe encephalopathy and coma can occur in approximately 10 to 20% of patients after intravenous infusion, and the incidence of neurotoxicity may be increased to 50% after oral administration because of differences in the preferential route of metabolism between the 2 routes of administration. Other adverse effects of ifosfamide include nephrotoxicity, alopecia, and nausea/vomiting. In general, intravenously administered mesna is associated with a low incidence of adverse effects; however, gastrointestinal disturbances are common following oral administration. Thus, ifosfamide/mesna is an important and worthwhile addition to the currently available range of chemotherapeutic agents. It has a broad spectrum of antineoplastic activity and causes less marked myelosuppression than many other cytotoxic agents. At present, the role of ifosfamide/mesna in refractory germ cell testicular cancer is clearly defined; however, its overall place in the treatment of other forms of cancer awaits delineation in future well-controlled comparative studies.
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PMID:Ifosfamide/mesna. A review of its antineoplastic activity, pharmacokinetic properties and therapeutic efficacy in cancer. 172 Mar 82

A total of 248 analyzable patients with Stages III-IV ovarian epithelial cancer (114 with and 134 without prior chemotherapy) were randomized to one of four cisplatin (DDP)-hexamethylmelamine (HMM) regimens. In each, HMM, 200 mg/m2 was given orally daily on days 8-21 of each 21-day cycle. DDP was given i.v. on Day 1 at a dose of 37.5 mg/m2 (regimens A and B) or 75 mg/m2 (regimens C and D). In addition, since pyridoxine administration has been reported to reduce the neurotoxicity of HMM, that agent was given at a dose of 300 mg/m2 orally on Days 1-21 in regimens B and D. Randomization was stratified for performance status (0-1, 2-3) and largest tumor diameter at entry (greater than 2- less than or equal to 10 cm, greater than 10 cm) for previously untreated patients, and for performance status and time from initial diagnosis to entry on study (less than or equal to 1 year, greater than 1 year) for previously treated patients. The overall response rate (PR + CR) was 54%, with 25% of patients achieving a complete response. The 61% response rate with the higher dose DDP regimens was significantly greater than the 47% response rate with the lower dose regimens (p = 0.031). Multivariate analysis identified higher DDP dose, age less than 60 years, no prior chemotherapy, small tumor bulk and favorable tumor grade as significant prognosticators for response. The overall median response duration was 8.3 months (range 1-70 months). Prior chemotherapy, pyridoxine administration, recent diagnosis, and large tumor size were identified by multivariate analysis as factors adversely affecting response duration. Patients treated with the higher dose DDP regimens had more severe nausea, vomiting, and neurotoxicity. This study demonstrates that the combination of DDP + HMM is an effective regimen for advanced ovarian carcinoma that yields response rates comparable to other more complex regimens, and that there is a dose-response relationship for DDP in ovarian cancer. Although pyridoxine administration significantly reduced neurotoxicity, its adverse effect on response duration suggests that the agent should not be administered with DDP or HMM. The mechanism by which pyridoxine may unfavorably affect response duration deserves further investigation.
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PMID:Hexamethylmelamine and low or moderate dose cisplatin with or without pyridoxine for treatment of advanced ovarian carcinoma: a study of the Eastern Cooperative Oncology Group. 173 9

Combination chemotherapy with Cyclophosphamide, Adriamycin and Cisplatin (CAP) is one of the most effective chemotherapies for ovarian cancer. Severe vomiting induced by this treatment may cause a disorder of the serum electrolytes. Severe hyponatremia was observed in one patient who complained of convulsions and unconsciousness. Accordingly we studied the disorder of serum electrolytes in 158 courses of CAP treatment (44 patients) during the five years from 1984 to 1988. The serum electrolytes were influenced by the amount of vomiting in this study. Consequently frequent examination of serum electrolytes is necessary during this treatment.
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PMID:[Disorder of serum electrolytes following CAP therapy]. 174 61


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