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)

In contrast to the broad experience concerning the therapeutic use of carboplatin, only limited data are available regarding the patterns of carboplatin-induced emesis, one of its most distressing side effects. This study reports frequency, severity and time course of carboplatin-induced vomiting and nausea refractory to 5-HT3 antagonism. A total of 216 patients receiving single-day carboplatin-based chemotherapy regimen were enrolled into an open multicenter study focusing on the safety and efficacy of ondansetron 8 mg t.d.s. Emesis on day 1 occurred in 22% and nausea in 75% of the patients; 44% of patients reported some degree of vomiting within the 5 days observation period. The risk for emesis and nausea over 2-5 days was increased in patients suffering from emesis on day 1 (relative risk 2.25 for vomiting and 2.84 for nausea, respectively). The median cumulative number of emetic episodes was 0 for all patients and 4 for the patients who did vomit at least on 1 day. Vomiting began on average 1.77 days following chemotherapy administration. The mean duration of vomiting was 2 days and 3.1 days for nausea. Carboplatin showed a monophasic prolonged pattern of emesis. The combination with cyclophosphamide led to an earlier onset and a higher frequency of vomiting. The analysis of the pattern of emesis refractory to 5-HT3 receptor blockade should help to describe the course of emesis, which is probably triggered through a 5-HT3 receptor-independent mechanisms.
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PMID:Pattern of carboplatin-induced emesis. The German Ondansetron Study Group. 884 74

In studies conducted by the Eastern Cooperative Oncology Group, treatment with either paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) or carboplatin was associated with an improvement in 1-year survival in patients with stage IV non-small cell lung cancer (NSCLC). Based on these findings, a phase II trial of carboplatin plus paclitaxel was conducted in patients with advanced NSCLC to determine the activity and toxicity of this regimen. Eligibility requirements included stage IIIB or IV histologically confirmed NSCLC, Eastern Cooperative Oncology Group performance status of 0 to 2, no prior chemotherapy, and adequate hematologic, renal, hepatic, and cardiac functions. Paclitaxel was administered intravenously over 24 hours at a dose of 135 mg/m2 (28 patients) or 175 mg/m2 (23 patients), followed by a 1-hour infusion of carboplatin on day 2. Carboplatin was administered at a dose of 300 mg/m2 (16 patients) or, using the Calvert formula, a dose calculated to achieve an area under the concentration-time curve of 6 mg/mL x min (35 patients). Treatment was repeated every 28 days for a total of six cycles. Among the 51 eligible patients, 34 were men and 17 were women; their median age was 60 years and their median Eastern Cooperative Oncology Group performance status was 1. Six patients had stage IIIB and 45 had stage IV disease. Grade 3 or 4 granulocytopenia and thrombocytopenia were observed in 47% and 3% of treatment cycles, respectively. The most common nonhematologic toxicities noted included nausea and emesis, neuropathy, and arthralgia and myalgia. There were no complete responses and 14 partial responses, for an overall response rate of 27% (95% confidence interval, 17% to 41%). Median survival was 38 weeks and the survival rate at 1 year was 32%. Paclitaxel plus carboplatin, as given in this study, was found to be a moderately active regimen in patients with advanced NSCLC. This regimen warrants comparison with existing cisplatin-based regimens in a prospective randomized trial.
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PMID:Paclitaxel plus carboplatin in the treatment of patients with advanced lung cancer: a Vanderbilt University Cancer Center phase II trial (LUN-46). 900 20

It is reported that the combination of cisplatin (CDDP) and carboplatin (CBDCA) is synergistic in vitro. The objective of this study was to evaluate the therapeutic effect and safety of the two platinum compounds in combination with etoposide in the treatment of non-small-cell lung cancer (NSLC). Forty patients were registered. Based on the results of a phase I study, patients were treated with CDDP (80 mg/m2 i.v. on day 1), CBDCA (280 mg/m2 i.v. on day 1), and etoposide (80 mg/m2 i.v. on days 1-3). Of the 40 patients, 30 were men and 10 women. Histology revealed adenocarcinoma(AC) (n = 20), squamous cell carcinoma(SCC) (n = 18), and large cell carcinoma(LCC) (n = 2). Staging: IIIA (n = 3); IIIB (n = 17); and IV (n = 20). A 32.5% overall response rate [13 of 40; 95% confidence interval (CI) 18-47%] was achieved. The response rates in patients with SCC and AC were 55.6 and 10.0% (p < 0.005), respectively. The median duration of response was 47.1 weeks and the overall median survival time was 57.1 weeks. Leukopenia and thrombocytopenia--World Health Organization (WHO) grade IV--occurred in nine and 11 patients, respectively. Nonhematological toxicities were mainly nausea, vomiting, and alopecia. In conclusion, further investigations of this regimen are warranted in the treatment of NSLC.
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PMID:A phase II study of carboplatin-cisplatin-etoposide combination chemotherapy in advanced non-small-cell lung cancer. 902 Feb 88

Recently, a randomized study conducted by the Gynecologic Oncology Group (GOG 111) demonstrated that, given by a 24-hour infusion, the combination of cisplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is superior to combination cisplatin/cyclophosphamide in previously untreated patients with advanced ovarian cancer. This combination, however, necessitates hospitalization. Combination paclitaxel/carboplatin would be expected to induce fewer nonhematologic side effects but may be more myelotoxic. Thus, we started a phase I dose-escalation study to determine the maximal tolerated dose of paclitaxel given as a 3-hour infusion in combination with carboplatin, both drugs administered every 21 days. The paclitaxel dose was escalated by increments of 25 mg/m2, starting at 135 mg/m2 (level 1), 160 mg/m2 (level 2), 185 mg/m2 (level 3), and 210 mg/m2 (level 4). Carboplatin was administered to achieve an area under the concentration-time curve of 5, using the Calvert formula For study levels 5 and 6, the carboplatin dose was targeted at area under the concentration-time curves of 6 and 7.5, respectively, and was combined with a fixed paclitaxel dose of 185 mg/m2. Thirty previously untreated patients with stage IIC to IV ovarian cancer were enrolled. Nonhematologic toxicity, including nausea/vomiting and arthralgia/myalgia, was mild. Across all dose levels, a total of 16 patients developed peripheral neurotoxicity (World Health Organization grades 1 and 2). At dose level 5, one patient experienced reversible grade 4 neurotoxicity. Neutropenia was the principal dose-limiting hematologic toxicity. During 33 (31%) of 106 courses, World Health Organization grade 4 neutropenia was observed. Granulocyte colony-stimulating factor was required in only 7.6% of courses. Thrombocytopenia was less than that expected when carboplatin is given alone. Clinical responses were observed in eight of 14 patients, for an overall response rate of 57%. The combination of carboplatin plus paclitaxel was found to be an active regimen. This trial demonstrates that carboplatin dosed by the Calvert equation and 3-hour paclitaxel can be combined safely at full therapeutic doses for six or more courses in patients with advanced epithelial ovarian cancer.
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PMID:Paclitaxel combined with carboplatin in the first-line treatment of advanced ovarian cancer: a phase I trial. 904 30

Evaluation of the relationship between parameters of serotonin (5-HT) metabolism and emesis in platinum-based chemotherapy. Female patients receiving chemotherapies containing either cisplatin (35 patients; 80 courses) or carboplatin (65 patients; 102 courses) were recruited. Recording of emesis and measurements of urinary 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of 5-HT, was performed over 3 days. Comparisons were performed for single-agent cisplatin (DDP) versus single-agent carboplatin (CBDCA), single-agent high-dose DDP (> or = 75 mg/m2) versus high-dose DDP combined with cyclophosphamide, high-dose versus low-dose DDP (< or = 50 mg/m2), and single-agent CBDCA versus a combination with alkylating agents. Cisplatin induced both a significantly higher frequency of emesis and a significantly higher increase of 5-HIAA excretion than carboplatin. The velocity of 5-HIAA increase may correlate better with emetogenic potential than peak 5-HIAA excretion levels. The increase of 5-HIAA excretion induced by cisplatin was limited to day 1. Higher cisplatin doses showed both a higher emetogenic potential and a more pronounced increase in urinary 5-HIAA on day 1. No significant difference was found when single-agent cisplatin was compared with cisplatin combined with cyclophosphamide. In contrast, a combination of carboplatin with alkylating agents induced a larger increase in urinary 5-HIAA and showed a higher emetogenic potential than single-agent carboplatin. Low-dose cisplatin induced less emesis than carboplatin combination therapy, but induced a larger increase in urinary 5-HIAA. Our findings provide evidence for a relationship between emetogenic potential and patterns of 5-HIAA excretion following platinum-based chemotherapy.
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PMID:The relationship between parameters of serotonin metabolism and emetogenic potential of platinum-based chemotherapy regimens. 917 67

Carboplatin/etoposide is an active regimen in the treatment of small cell lung cancer. This phase II trial evaluated whether adding paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to this two-drug combination might increase its efficacy. Since April 1996, 55 patients were entered into the ongoing protocol. To date, 35 patients are evaluable for efficacy and toxicity. Most of the evaluable patients are male (28). The patients' median age is 60 years (range, 36 to 74 years); 32 patients have Eastern Cooperative Oncology Group performance status ratings of 1, and the balance are Eastern Cooperative Oncology Group performance status 0. All patients had limited-stage disease. Patients received paclitaxel 175 mg/m2 via 1-hour intravenous infusion on day 1, carboplatin dosed to an area under the concentration-time curve of 5, also on day 1, and oral etoposide 100 mg on days 2 through 8. Overall, 31 patients responded to paclitaxel/carboplatin/etoposide therapy, including complete response in 13 patients (37.1%) and partial response in 18 patients (51.4%). Disease was stable in three patients (8.6%) and disease progressed in one (2.0%). Hematologic toxicity included neutropenia (World Health Organization grade 3 in 24.1% of patients, grade 4 in 31.3%), anemia (4% grade 3, no grade 4), and thrombocytopenia (3.2% grade 3, 2.1% grade 4). Nonhematologic adverse events included minor nausea/vomiting (1.5% grade 3, 9.2% grade 2), polyneuropathy (2.3% grade 2, 17.5% grade 1), and myalgia/arthralgia (8.2% grade 2, 16.4% grade 1). Paclitaxel/carboplatin/etoposide is active in small cell lung cancer with moderate toxicity and good subjective tolerance. There were no life-threatening hematologic or nonhematologic complications in this phase II trial.
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PMID:Paclitaxel, carboplatin, and oral etoposide: a phase II trial in limited-stage small cell lung cancer. 933 Nov 41

Prolonged oral administration of etoposide may have a theoretical advantage over intravenous infusion, and carboplatin has a more favorable toxicity profile than cisplatin. A combination of carboplatin 300 mg/m2 and oral etoposide 40 mg/m2/day for 21 days was assessed in 74 (42 limited, 32 extensive disease) previously untreated patients with small-cell lung cancer. Response rate was 69% (CR 19%, PR 50%,) for limited disease and 72% (CR 9%, PR 63%) for extensive disease. Median response duration and overall survival was 6.6 and 10.1 months for limited disease, and 5.3 and 9.1 months for extensive disease, respectively. One-year and two-year survival was 36 and 10% for limited disease and 31 and 2% for extensive disease, respectively. The major toxicity was hematological with grade 4 or greater neutropenia in 36% and grade 4 thrombocytopenia in 16%, and one patient died of neutropenic fever. Non-hematologic toxicities were mild and grade 3 emesis was observed in 5% of patients. Carboplatin combined with 21-day oral etoposide showed only modest activity against small-cell lung cancer with high toxicity and did not merit further evaluation.
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PMID:A phase II study of carboplatin and prolonged administration of oral etoposide in patients with small-cell lung cancer. 949 98

Our objective was to determine the maximum tolerated dose of cyclosporin A (CsA) delivered as a loading dose (LD) and continuous i.v. infusion (CI) in combination with carboplatin in patients with refractory gynecologic cancers. Twenty-nine heavily pretreated patients (25 ovarian epithelial, 2 cervical, and 2 endometrial carcinomas) received 113 cycles of CsA and carboplatin from September 1989 to September 1991. Twenty-four of these 29 carcinomas were strictly defined to be platinum resistant. CsA was administered as a LD escalated from 6 to 10 mg/kg followed by a 24-h CI from 2.5 to 14.5 mg/kg/day. Carboplatin was targeted to an area under the time versus concentration curve (AUC) of 6 mg/ml x min and was not dose escalated. Whole-blood CsA concentrations (fluorescence polarization immunoassay) at the maximum tolerated dose (10 mg/kg LD, 14.5 mg/kg/day CI) ranged from 2.4 to 3.0 microgram/ml over 12 h. Estimated median carboplatin AUC, based on calculated carboplatin clearance, was 7.9 mg/ml x min. The dose-limiting toxicity of the combination of CsA and carboplatin was grade 4 thrombocytopenia. Grade 3 or 4 thrombocytopenia occurred in 35% of the patients, which could be explained by the effects of carboplatin (AUC of 6 mg/ml x min) alone. Overall, neutropenia occurred in 24% of the patients and anemia in 17% of the patients. Grade 3 or 4 nausea or vomiting was noted in 10 and 14% of the patients, respectively. Grade 3 hypertension during CsA administration occurred in 14% of the patients. No grade 3 or 4 nephrotoxicity was seen in this trial. Three objective responses were noted: one complete response (11 months) and one partial response (5 months), both in potentially platinum-sensitive patients with platinum-free intervals of only 9 months each. One platinum-resistant patient had a partial response for 21 months. Five additional patients experienced >75% reduction of CA-125 or a return to a normal CA-125 titer. We concluded that whole-blood CsA concentrations of >3.0 microgram/ml (as seen when CsA is used as a modulator of multidrug resistance) were not achievable in this combination with carboplatin in this population of heavily pretreated gynecologic cancer patients. However, because CsA is used in this trial as a chemosensitizer in platinum-sensitive tumors and as a chemomodulator of platinum resistance, we targeted a CsA concentration of >1.0 microgram/ml, which was achieved. The CsA dose recommended for a Phase II trial of this combination is 10 mg/kg LD and 11.6 mg/kg/day CI, which results in blood CsA concentrations ranging from 1.2 to 1.3 microgram/ml over 12 h. Responses in this population of refractory gynecologic cancer patients are unusual, and these encouraging results form the basis for a Phase II trial of this combination.
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PMID:Phase I trial of intravenous carboplatin and cyclosporin A in refractory gynecologic cancer patients. 981 19

Between 1/1990-8/1997 two courses of single agent Carboplatin had been given to 36 patients with clinical stage I seminoma. Within an median follow up period of 52 months (17-88) 29 out of 34 patients were analyzed retrospectively. During this period no recurrences had been noted and nobody of our patients died (0% relapsrate, 100% survival-rate). The Carboplatin-therapy was well tolerated. Myelosuppression after chemotherapy was mild (WHO grade I). The experienced acute toxic side effects (max. grade II WHO) during and after chemotherapy had been nausea (37%), vomiting (14%) and mild hairloss (11%). Until now no long term side effects were noticed. A standardized questionnaire had been used to evaluate the impairment of quality life after single agent carboplatin therapy. After a minimum of one year follow up averagly 79% (62-92%) of the asked patients showed no impairment of their quality of life, whereas 19% (8-38%) of the people experienced mild impairment of their quality of life. Because of the shown low recurrence rate, the minimal toxicity and no relevant impairment of the quality of life single agent carboplatin therapy will be an alternative approach for clinical stage I seminoma.
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PMID:[Carboplatin monotherapy in clinical stage I of seminoma. An acceptable alternative?]. 988 92

The effects of oral antiemetic drugs on delayed emesis induced by emetogenic chemotherapy were studied in seventeen patients (43 courses) with gynecological malignancies. On day 1, all patients received intravenous granisetron (40 micrograms/kg) and methylprednisolone (250 mg/body) for the control of acute emesis 0-24 hrs after receiving CDDP or CBDCA. Then they received each oral maintenance drug (dexamethasone 4 mg/day, ondansetron 4 mg/day and metoclopramide 40 mg/day) for the control of delayed emesis from day 2 to day 5. Efficacy rates for delayed emesis were 82.4% in dexamethasone, 75.0% in metoclopramide and 50.0% in ondansetron. The complete response for delayed nausea was 88.5% in metoclopram ide, and the complete response for delayed anorexia of 64.7% in dexamethasone was higher than for other oral drugs. The results suggest the usefulness of oral antiemetic therapy of dexamethasone plus metoclopramide or ondansetron for delayed emesis induced by cancer therapy.
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PMID:[Clinical studies of oral antiemetic drugs on delayed emesis induced by cancer chemotherapy]. 998 7


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