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)

JM216 [bis-acetato-ammine-dichloro-cyclohexylamine-platinum(IV)] is an oral platinum complex that is currently in phase II trials in ovarian cancer and lung cancer on a daily-times-5 schedule. This trial examined an alternative schedule of two doses given 12 h apart, which may be better tolerated by patients. A total of 19 patients were given 50 cycles of treatment at doses ranging from 150 to 350 mg/m2 b.i.d. The study was stopped before the MTD was reached due to non-linear pharmacokinetics. Toxicity was similar to that encountered in previous phase I studies, with nausea, vomiting and diarrhoea being seen at all dose levels, although this was generally mild and short-lived, and grade 3 and 4 myelosuppression being seen at dose levels ranging from 250 to 350 mg/m2. There was no nephro-, oto-, or neurotoxicity, but one patient had an allergic reaction at 300 mg/m2 on the fifth and sixth cycles. No response was seen, but two patients with mesothelioma had stable disease and received six cycles. There was considerable interpatient variability in plasma pharmacokinetics at all dose levels. There was no relationship between dose and AUC (dose 1 and dose 2) or Cmax after dose 1. In a limited number of patients the first dose was given in the morning rather than in the evening, apparently resulting in lower AUC, Cmax and Tmax values at the 250-mg/m2 dose level, but this was not seen in one patient at 300 mg/m2. This study confirms that the pharmacokinetics of JM216 is non-linear and highly variable due to saturable absorption and that the daily times 5 schedule is the optimal schedule for further phase II trials.
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PMID:Phase I study of oral JM216 given twice daily. 965 14

At the present time 5-HT3 antagonists in combination with corticosteroids represent the best prophylaxis and treatment of acute vomiting and nausea in highly emetogenic cancer chemotherapy. However, 24 h after chemotherapy 5-HT3 antagonists are no longer superior to benzamides for prevention of delayed symptoms. All recommendations for use of corticosteroids in delayed nausea and vomiting basically rely on one small study by Kris et al. [J Clin Oncol 1989;7:108-114]. Since the use of corticosteroids in cancer chemotherapy remains controversial, this single-blind, randomised, prospective trial was initiated to re-evaluate the benefits of corticosteroids during the days after chemotherapy. Thus patients treated for ovarian cancer received 5 mg tropisetron (Navoban) plus 20 mg dexamethasone for the prevention of acute vomiting and nausea in cis-platinum-containing chemotherapy (50 mg). Twenty-four hours after the beginning of chemotherapy 49 patients were randomised to receive 3 x 100 mg alizapride (Vergentan) plus a placebo medication (group A) and 47 patients to receive 3 x 100 mg alizapride plus 3 x 4 mg dexamethasone (group B) for 3 days depending on the incidence of acute vomiting beginning on day 2. The well-being of both groups was compared using objective and subjective parameters (Rotterdam Symptom Checklist). Major control of acute vomiting was achieved in 87.5% of the cases. The study was stopped after this interim analysis of 96 patients revealed no advantage of corticosteroids during the days after chemotherapy. Significant differences between both groups were detected only on a few days (day 6: objective nausea in favour of group A, day 4: objective vomiting in favour of group B, day 6: objective vomiting in favour of group A, day 3: constipation in favour of group A, days 4 and 5: difficulty concentrating in favour of group A, day 3: dry mouth in favour of group B). In contrast to acute nausea and vomiting the addition of corticosteroids is not beneficial in the prevention of delayed nausea and vomiting. Until better strategies are available the best prophylaxis of delayed symptoms is the control of acute nausea and vomiting using 5-HT3 antagonists plus corticosteroids. The use of benzamides has to be considered efficacious in the prevention of delayed vomiting and nausea.
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PMID:Does dexamethasone enhance the efficacy of alizapride in cis-platinum-induced delayed vomiting and nausea? 966 18

Some clinical parameters play a role in developing effective antiemetic therapy. In the present study, 310 patients entered and 301 were evaluable. They received cisplatin based combination chemotherapy (100 mg/m2), with antiemetic therapy based in metoclopramide, at a standard dose and schedule (2 mg/kg in 5 doses). Patient characteristics such as age, sex, performance status (Karnofsky), site of primary tumor, weight loss >15%, previous chemotherapy, previous radiotherapy, history of vomiting during pregnancy, additional drugs (dexamethasone, alprazolam), in the antiemetic regimen were included in the evaluation. We also studied the manifestation of anxiety and depression and the presence of psychosocial problems related to therapy, evaluated them with specific psychological indexes modified for our study. We evaluated incidence of vomiting, retches, and nausea, with several scales. We distinguished three groups of factors influencing nausea and vomiting. Factors that predicted for increased nausea and vomiting was gender (women), stress and age (younger patients experienced more prolonged duration and higher grades of nausea). The addition of alprazolam (a sedative drug) and dexamethasone, was associated with decreased incidence of nausea and vomiting. The weight loss (increased nausea and decreased vomiting control according to Gralla's scale). Previous chemotherapy decreased the number of patients without nausea and vomiting control according to Gralla's scale. Patients with previous radiotherapy presented an increased grade of nausea. Patients with head and neck cancer presented less nausea with shorter duration, less frequent episodes of vomiting. Patients with ovarian cancer presented increased mean number of retches. In conclusion, despite difficulties in assessing nausea and vomiting among clinical trials, several factors, especially stress, gender, weight loss, additional drugs (corticosteroids and sedatives) may play an important role in modulating the antiemetic response.
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PMID:Factors that influence the antiemetic activity of metoclopramide to cisplatin based chemotherapy. 968 26

The topoisomerase I inhibitor topotecan has shown antitumour activity against a variety of tumour types in vitro and in vivo. Topotecan in combination with drugs that induce DNA damage generally results in synergistic killing of tumour cells in vitro. As the activity of topotecan is related to exposure time, the drug is administered by intravenous infusion either continuously or once daily over a 30-minute period for several consecutive days. A 30-minute infusion of topotecan 1.5 mg/m2 on 5 consecutive days every 3 weeks produced response rates of up to approximately 20% in patients with advanced ovarian cancer who had failed to respond to platinum-based regimens or relapsed after initial response to such regimens. No significant differences in efficacy were apparent between topotecan and paclitaxel in a phase III study in patients with recurrent ovarian cancer, although a trend in favour of topotecan was evident for all major efficacy parameters. Non-cumulative myelosuppression, including neutropenia, thrombocytopenia and anaemia, is the dose-limiting toxicity associated with topotecan. Myelo-suppression was significantly more common with topotecan than with paclitaxel in a single comparative study. Non-haematological adverse events in topotecan recipients are generally mild and include alopecia, nausea, vomiting, and other gastrointestinal problems. Thus, topotecan has modest efficacy in the treatment of recurrent advanced ovarian cancer, with clinical activity similar to that of paclitaxel in a large randomised phase III study in this setting. Combinations of paclitaxel and a platinum compound are being used increasingly for first-line therapy, although relapse rates remain significant. Topotecan is therefore a suitable second-line option, providing antitumour response for some patients whose disease has relapsed after, or is refractory to, platinum-based therapy. Its wider potential when used either alone or in combination regimens should become clearer from ongoing studies.
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PMID:Topotecan. A review of its potential in advanced ovarian cancer. 980 12

We conducted multi-site early phase II trial or oral etoposide administered for 21 consecutive days in patients with cervical or ovarian cancer in cooperation with 19 institutes. Fifty mg/body of oral etoposide was administered daily for 21 consecutive days. Cycles were repeated every 28 days. In cervical cancer, 24 patients were enrolled and 17 of them were evaluated. The overall response rate including CR and PR was 23.5% (4/17). In ovarian cancer, 18 patients out of 21 enrolled were evaluated. The overall response rate was 16.7% (3/18). The primary toxicity observed was myelosuppression such as leukopenia, neutropenia, hemoglobin decrease and thrombocytopenia. Other adverse effects were anorexia, nausea, vomitting, fatigue, alopecia and stomatitis. From these results we concluded that oral etoposide administered for 21 consecutive days was effective against cervical cancer.
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PMID:[Early phase II trial of oral etoposide administered for 21 consecutive days in patients with cervical or ovarian cancer. ETP 21 Study Group--Cervical-Ovarian Cancer Group]. 983 8

Topotecan does not convincingly alter the grim prognosis of ovarian cancer in failure or relapse after treatment with platinum salts. The only comparative trial has not yet been published; available results suggest that 20% of women had at least a partial response on topotecan, compared to 14% on paclitaxel (no statistically significant difference). The place of paclitaxel in the treatment of ovarian cancer also remains to be determined, especially in combination with other drugs. Like paclitaxel, topotecan has marked haematological and gastrointestinal toxicity: nausea, vomiting, diarrhoea and stomatitis. Topotecan solution does not contain the solvent Cremophor EL degrees , contrary to paclitaxel solution. It does not therefore require preliminary steroid administration, and does not prohibit the use of PVC-based infusion devices.
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PMID:Topotecan: new preparation. No proven benefit. 1018 83

This review summarizes the results reported in preclinical and clinical trials of three novel anticancer drugs developed and tested in Japan. In phase II trials, Irinotecan, a semisynthetic analog of camptothecin, has yielded response rates exceeding 20% in non-small-cell lung cancer, small-cell lung cancer, breast cancer, gastric cancer, colorectal cancer, ovarian cancer, uterine cervical cancer, and non-Hodgkini's lymphoma. It was modestly active on pancreatic cancer and was not active on acute leukemias. Dose-limiting toxicities were leukopenia and diarrhea, and other major toxicities were nausea, vomiting, and alopecia. Amrubicin, a totally synthetic anthracycline, exhibited both higher efficacy on human tumor xenografts and cardiotoxicity milder than that of doxorubicin in preclinical studies. The dose-limiting toxicity in phase I trials was leukopenia. In phase II trials, amrubicin has shown activity equivalent to that of doxorubicin on non-Hodgkin's lymphoma, response rates exceeding 20% on non-small-cell lung cancer, and a response rate of 78.8% on untreated extensive-stage small-cell lung cancer. S-1 is an oral formulation consisting of ftorafur (an analog of 5-fluorouracil), 5-chloro-2, 4-dehydropyrimidine, which inhibits degradation of 5-fluorouracil, and potassium oxonate, which reduces gastrointestinal toxicity, at a molar ratio of 1:0.4:1. In phase I trials, dose-limiting toxicities (myelosuppression and gastrointestinal toxicities) were judged to be milder than those induced by UFT (ftorafur plus uracil). The response rates obtained in phase II trials were 40-49% on advanced gastric cancer, 35.5% on colorectal cancer, 37.5% on head and neck cancer, and 40.7% on breast cancer.
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PMID:Novel anticancer drugs in Japan. 1023 66

The purpose of the present study was to examine whether its is possible to successfully replace ondansetron (OND) with metoclopramide (MCP) in patients exposed to moderately emetogenic chemotherapy who did not experience severe nausea and vomiting while undergoing OND treatment during their first chemotherapy cycle. After switching to MCP, patients continued with this drug for three cycles, provided that they had adequate control of nausea and vomiting. Otherwise, they were switched back to OND. There were 76 patients, 60 women and 16 men, whose median age was 56 (mean 58) years. Karnofsky performance status score was 100 in 18 patients, 90 in 23, and 80 in 11 patients. No patient had previous chemotherapy. Thirty-four patients had breast cancer and received fluorouracil 500 mg/m2, epirubicin 100 500 mg/m2, and cyclophosphamide 500 mg/m2. Twelve patients had small cell lung cancer and received carboplatin 400 mg/m2 + etoposide 120 mg/m2 x 3 days. Twenty patients with ovarian cancer received carboplatin 350 mg/m2 and cyclophosphamide 500 mg/m2. Ten patients had cancer of unknown primary and received carboplatin 400 mg/m2, epirubicin 60 mg/m2, and etoposide 120 mg/m2 x 3 days. The OND schedule consisted of methylprednisolone 40 mg intravenous bolus followed by OND 8 mg in a 15-min infusion before chemotherapy, followed by OND 4 mg orally x 3 on the same and the next 2 days. Patients who did not experience nausea and vomiting with OND continued with an MCP schedule consisting of methylprednisolone 40 mg bolus followed by MCP 2 mg/kg in a 15-min infusion before chemotherapy, followed by MCP (20 mg x 4 on the day of therapy and the next 2 days after). Patients who failed with MCP or OND continued with OND. Considering our results as a whole, the intensity of nausea does not appear to influence the results of Gralla's scale. The results of Gralla's scale do not appear to be affected by the analysis of the antiemetic results and nausea on the next 2 days following chemotherapy administration. Overall, patients received 145 cycles with OND and 159 cycles with MCP. Of the 76 patients receiving OND-based antiemetic regimen during the first cycle, 13 (21%) experienced severe vomiting (Grade 2, 3) and the remaining 63 (79%) had mild or no vomiting (Grade 0, 1). Patients with Grade 0, 1 vomiting (63, 83%) continued with MCP in the second cycle. The final number of patients who failed on MCP, after 4 cycles of chemotherapy increased to 33 (43%); 43 (57%) were able to complete chemotherapy with MCP. Headache occurred in 15 (10%) cycles with OND and 8 (5%) with MCP. Flushing was noted in 12 (8%), and constipation occurred in 43 (30%) of OND cycles, and extrapyramidal manifestations occurred in 3 (5%) of patients receiving MCP. Diarrhea was noted in 3 (2%) of cycles with OND and in 28 (18%) with MCP. The cost ratio between MCP and OND was 1:14. If we administered OND only in patients who needed it, the overall cost decreased to 44%. Following the strategy applied in the present study, the cost decreased to 47%.
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PMID:Antiemetic prophylaxis with ondansetron and methylprednisolone vs metoclopramide and methylprednisolone in mild and moderately emetogenic chemotherapy. 1051 44

Individual cancer patients differ in their nausea/vomiting response to chemotherapy. It is not known why patients receiving the same chemotherapy have different severity of side effects. Several lines of research implicate the autonomic nervous system (ANS) in the development of chemotherapy-induced nausea. We examined the association between autonomic reactivity and the level of nausea experienced following chemotherapy in 20 patients with ovarian cancer treated with cisplatin or carboplatin who received the same antiemetic. We applied eight common non-invasive clinical tests of autonomic function prior to inpatient chemotherapy treatment, 2 h after treatment and again 24 h following treatment. Two hours after chemotherapy and before any nausea was reported by the patients, the nine patients who subsequently experienced high levels of nausea had a greater overall percentage of abnormal clinical ANS tests than the 11 patients who subsequently developed low levels of nausea (P < 0.01). Twenty-four hours after treatment, the overall number of abnormal autonomic tests remained non-significantly higher than at the pretreatment baseline for the high nausea group. Demographic and clinical characteristics were not related to chemotherapy-induced nausea in this sample. Autonomic reactivity appears to be related to the development of nausea following chemotherapy. Further investigation of ANS involvement in chemotherapy-induced nausea could increase understanding of nausea etiology and potentially lead to the prediction of susceptible patients.
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PMID:Changes in clinical measures of autonomic nervous system function related to cancer chemotherapy-induced nausea. 1058 24

Forty-three patients with ovarian cancer were entered on this trial and treated with intravenous (iv) cyclophosphamide (C) and doxorubicin (A), and intraperitoneal (ip) cisplatin (DDP), every 21 days for eight cycles. Following iv hydration, the cisplatin was administered through an intraperitoneal catheter in 2 L of 0.9% normal saline with a 4-h dwell. All patients are evaluable for overall and progression-free survival with a median follow-up of 70 months (range: 3-162 months); 39 patients are evaluable for response. All complete responses were surgically confirmed. The median age was 59 (range 28-82 years); 3 patients were stage IC, 5 were IIC, 14 patients were stage III (optimally debulked), 14 patients were stage III (suboptimally debulked), and 7 patients were stage IV. Two patients had received prior alkylator therapy. Six of 8 patients with Stage IC or II remain without evidence of disease at a mean of 12 years following chemotherapy. Of 14 optimally debulked stage III patients, there were 7 complete responses, 3 partial responses, 1 patient with stable disease, and 3 inevaluable patients. Of 14 suboptimally debulked stage III patients there were 4 complete responses, 4 partial responses, 3 with stable disease, 2 progressions on treatment, and 1 inevaluable patient. Five-year progression-free and overall survivals for stage III optimally debulked patients are 21 and 64%, respectively. At 10 years, progression-free and overall survivals for this group are 21 and 29%, respectively. Toxicity included neutropenia (complicated by sepsis in 2 patients), infrequent thrombocytopenia, and mild anemia. Three patients developed transient serum creatinine elevations >2.0 mg/dl; however, decreased creatinine clearance was noted in 93/258 (36%) of evaluable courses which required a cisplatin dose reduction per protocol. Controllable hypomagnesemia, nausea, and emesis were also observed. We conclude that the combination of iv CA and ip DDP is an effective regimen with long-term progression-free and overall survivals that compare favorably with those of other published studies of intravenous or intraperitoneal chemotherapy. This report is unusual in terms of the prolonged follow-up for all patients enrolled. These long-term results lend further support to recently published trials documenting the efficacy of intraperitoneal chemotherapy for patients with this disease.
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PMID:Phase II trial of intraperitoneal cisplatin with intravenous doxorubicin and cyclophosphamide in previously untreated patients with advanced ovarian cancer-long-term follow-up. 1060 Mar


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