Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Little information exists on the functional impact of effective antiemetic protection. In the present study, the Functional Living Index-Emesis (FLIE), was used to assess patient-reported impact of chemotherapy-induced nausea and vomiting (CINV) after administration of a new NK-1 receptor antagonist (aprepitant). Cisplatin-treated patients in a double-blind randomised trial received either aprepitant+dexamethasone+ondansetron on day 1 and aprepitant+dexamethasone on days 2-5 or standard antiemetic therapy (dexamethasone and ondansetron on day 1 and dexamethasone on days 2-5). Emetic events, nausea ratings and rescue medications were recorded in a 5-day diary and the FLIE was completed on day 6. Compared with standard therapy, significantly more patients treated with the high dose aprepitant regimen achieved a Complete Response (71 vs 44%, P<0.001) and also reported no impact on daily life as indicated by the FLIE total score (84 vs 66%, P<0.01). Use of the FLIE demonstrated that improved control of emesis was highly effective in reducing the impact of CINV on patients' daily lives.
 ...
PMID:Functional relevance of antiemetic control. Experience using the FLIE questionnaire in a randomised study of the NK-1 antagonist aprepitant. 1282 42

This phase I study was conducted to determine the recommended phase II doses, safety profile, and antitumour activity of a combination regimen of cisplatin, irinotecan, and epirubicin administered every 3 weeks in patients with advanced solid tumours. Cisplatin and epirubicin were given at fixed doses of 50 and 60 mg m(-2), respectively. The irinotecan dose was escalated at 10 mg m(-2) increments from a starting dose level of 70 mg m(-2). Epirubicin, irinotecan, and their metabolites were measured with HPLC methods. In all, 35 patients received 141 courses of treatment. Irinotecan dose was escalated in seven cohorts up to 130 mg m(-2), and then finally de-escalated to 110 mg m(-2). The dose-limiting toxicity was neutropenic fever. Nonhaematologic toxicities included mild to moderate nausea/vomiting, diarrhoea and fatigue. Of 34 patients with evaluable disease, one patient had a complete response and nine patients had partial response, yielding an overall response rate of 29.4%. Pharmacokinetic parameters of epirubicin were not affected by the sequence of drug administration. However, the AUCs of irinotecan and its metabolites were increased significantly when irinotecan and epirubicin were administered concurrently. This combination regimen has promising broad antitumour activity, and will be further evaluated in phase II studies in multiple tumour types.
 ...
PMID:Phase I study of cisplatin, irinotecan, and epirubicin administered every 3 weeks in patients with advanced solid tumours. 1291 67

A dose-escalation study was conducted for patients with metastatic gastric cancer to determine the recommended dose of weekly intravenous (i.v.) cisplatin combined with a fixed dose of a new oral dihydropyrimidine dehydrogenase-inhibitory fluoropyrimidine, S-1, on an outpatient basis. Secondary endpoints were to define the toxicity profile and to determine tumour responses. S-1 was fixed at a dose of 70 mg/m(2)/day and was administered for 2 weeks followed by a 1-week rest. Three dose levels of cisplatin (10, 15 and 20 mg/m(2)) were studied. Cisplatin was infused over 30 min on days 1 and 8. 20 patients were enrolled. No dose-limiting toxicities (DLTs) were recorded during the administration of cisplatin up to 20 mg/m(2), except for grade 3 diarrhoea and stomatitis in one patient at dose level 3. No grade 4 adverse events occurred. However, grade 2 gastrointestinal adverse reactions, such as nausea and anorexia, were seen in 7 of 13 patients at dose level 3 within the first two treatment cycles. This was determined to be the maximum acceptable level that would not negate the advantages observed with use of an oral drug such as S-1. An objective tumour response was seen at all dose levels, and the overall response rate in the 18 patients evaluated was 61%. A higher response rate of 78% was observed in 9 patients who had received no prior chemotherapy. Oral S-1 with weekly cisplatin is a feasible and promising combination regimen that is appropriate for an outpatient setting. A randomised phase II study comparing this combination with S-1 alone in chemo-nai;ve patients is warranted.
 ...
PMID:A phase I study of S-1 combined with weekly cisplatin for metastatic gastric cancer in an outpatient setting. 1455 24

Peritoneal mesothelioma is a rare malignancy that is seen in patients exposed to asbestos or in young women with no known exposure to asbestos. The clinical features of the disease are similar in these two groups, and include peritoneal carcinomatosis, ascites, thrombocytemia, systemic symptoms (fever and night sweats), and hypercoagulability. There is no known curative therapy for this disease. Cisplatin has activity in 25% of patients. Mesothelial cells are known to contain high levels of carboxylesterase, a key enzyme in the activation of Irinotecan (CPT-11) to SN-38. This retrospective review of our experience in combining cisplatin 50 or 60 mg/m2 i.v. or i.p. on day 1 with CPT-11 50 or 60 mg/m2 i.v. on day 1, 8, and 15. Courses were repeated every 4 weeks x 6. If i.p. administration of cisplatin were feasible, it was the preferred route. Response to treatment was based on RECIST criteria. Fourteen men and 3 women, median age 62 years (35-76 years) and median PS 1 (0-2) were treated. Median number of courses was two for nonresponders and six for responders. The overall response rate was 24%, but 76% of patients improved on treatment. Median survival is not reached. Grade > or = 2 side effects included anemia (n = 6), neutropenia (n = 3), nausea/vomiting (n = 4), and constipation (n = 2). Grade 1 side effects were fatigue, anorexia, weight loss, alopecia, diarrhea, neuropathy, and gastric reflux. There were no grade > or = 3 hematologic toxicities. The combination of cisplatin and CPT-11 is well tolerated and has clinical benefits in patients with peritoneal mesothelioma.
 ...
PMID:Cisplatin and irinotecan (CPT-11) for peritoneal mesothelioma. 1462 25

Cisplatin has been one of the most widely used and most effective cytotoxic agents in the treatment of malignancies but causes severe adverse reactions including nausea/vomiting, renal toxicity, gastrointestinal toxicity, peripheral neuropathy, asthenia, and ototoxicity. A liposomal formulation of cisplatin, Lipoplatin, was developed in order to reduce the systemic toxicity of cisplatin. A single treatment of rats with 30 mg/kg Lipoplatin resulted in no toxicity whereas 2 or 3 weekly administrations at 30 mg/kg to rats gave neutropenia but no nephrotoxicity. On the contrary, a single injection to rats of 5 mg/kg cisplatin resulted in severe nephrotoxicity. Thus, Lipoplatin is less toxic than cisplatin in rats. Intraperitoneal or intravenous injection of Lipoplatin to SCID (severe combined immunodeficient) mice with subcutaneous breast MCF-7 or prostate LNCaP human tumors resulted in size reduction of the tumors; histological examination of the treated tumors in xenografts was consistent with apoptosis in tumor cells; thus, Lipoplatin appears to exert its cytotoxic effects to tumors in a mechanism similar to that of cisplatin. The preclinical studies reported here set the foundation for the clinical use of Lipoplatin as an exciting new drug with lower toxicity than cisplatin, endowed with proapoptotic properties.
 ...
PMID:Low toxicity and anticancer activity of a novel liposomal cisplatin (Lipoplatin) in mouse xenografts. 1520 51

The primary objective of the present randomized phase III trial was to compare the 3-yr survival rate of patients treated with standard fractionated radiotherapy (RT) alone or with the same RT concomitantly with cisplatin (DDP) or carboplatin (Cb). From January 1995 until July 1999, 124 patients with histologically proven locally advanced non-nasopharyngeal head and neck cancer (HNC) were randomized to receive either RT monotherapy (70 Gy, Group A) or the same RT concomitantly with DDP (100 mg/m2 on d 2, 22, 42, Group B) or Cb (7 AUC on d 2, 22, 42, Group C). There were no significant differences in complete response rates between patients treated with RT alone or combined chemoradiotherapy. However, median time to progression (TTP) and overall survival (OS) were significantly longer in patients treated with concomitant chemoradiotherapy. Thus, median TTP was 6.3, 45.2, and 17.7 mo in groups A, B, and C respectively (p = 0.0002). Similarly, median OS was 12.2, 48.6, and 24.5 mo, respectively (p = 0.0003). At 3 yr follow-up, 17.5% of patients in group A were alive compared to 52% in group B and 42% in group C (p < 0.001). Patients treated with concomitant chemoradiotherapy experienced more frequently severe hematological toxicity. Also, severe nausea/vomiting was more pronounced in group B, as expected. The present study clearly demonstrated that concomitant chemoradiotherapy with platinum analogs significantly prolongs 3-yr survival and median OS in patients with locally advanced HNC compared to conventional RT alone.
 ...
PMID:Concomitant radiochemotherapy vs radiotherapy alone in patients with head and neck cancer: a Hellenic Cooperative Oncology Group Phase III Study. 1529 81

The purpose of this report is to summarize information on pemetrexed (LY231514; MTA; Alimta; Eli Lilly and Company; Indianapolis, IN), a drug recently approved by the U.S. Food and Drug Administration (FDA). The review of the efficacy and safety of pemetrexed is summarized below. Pemetrexed is a pyrrolopyrimidine antifolate. It inhibits thymidylate synthase, glycinamide ribonucleotide formyltransferase, and dihydrofolate reductase. In a single, randomized, single-blind, multicenter phase III trial, the efficacy and safety of pemetrexed combined with cisplatin (Platinol; Bristol-Myers Squibb; Princeton, NJ) were compared with those of single-agent cisplatin in 448 patients with malignant pleural mesothelioma. Two hundred twenty-six patients were randomized to receive pemetrexed and cisplatin, while 222 patients were randomized to receive cisplatin alone. The primary study end point was survival. Median survival times were 12.1 months for the pemetrexed plus cisplatin treated arm and 9.3 months for the cisplatin alone arm. Pemetrexed causes myelosuppression. The most common adverse events were neutropenia, fatigue, leukopenia, nausea, dyspnea, and vomiting. On February 4, 2004, pemetrexed was approved by the FDA in combination with cisplatin for the treatment of patients with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery. The recommended dose of pemetrexed is 500 mg/m(2) administered as an i.v. infusion over 10 minutes on day 1 of each 21-day cycle together with cisplatin at a dose of 75 mg/m(2) infused over 2 hours beginning 30 minutes after the pemetrexed infusion. Patients must receive oral folic acid and vitamin B(12) injections prior to the start of therapy and continue these during therapy to reduce severe toxicities. Patients should also receive corticosteroids with chemotherapy to reduce the risk of skin rashes. Approval was based on superior survival as a clinical benefit.
 ...
PMID:FDA drug approval summaries: pemetrexed (Alimta). 1547 32

Cisplatin, a cancer chemotherapy agent, like many toxins, produces emesis and nausea. Abdominal vagotomy, or treatment with 5-HT3 receptor antagonists, blocks cisplatin-induced emesis, which suggests that it produces (albeit indirectly) activation of 5-HT3 receptors on vagal afferent fibers. Cisplatin induces a large release of intestinal 5-hydroxytryptamine (5-HT) that enters the hepatic portal vein, which may activate vagal afferent fibers in the portal vein or liver to induce emesis or other side effects of treatment (e.g., reduced food intake). This study was conducted to assess the effects of cisplatin on gastrointestinal and portal vein/liver vagal afferent fibers by recording the neurophysiological responses of the common hepatic branch (CHB) of the vagus in the rat. The CHB contains vagal afferent fibers that innervate the gastrointestinal (GI) tract, portal vein, and liver. Cisplatin (10 mg/kg; jugular vein, j.v.) produced an increase in multi-unit CHB activity and this effect was blocked by a 5-HT3-receptor antagonist (Y-25130, 0.8 mg, j.v.). Cutting the gastroduodenal branch (GDB), a sub-branch of the CHB that contains GI afferent fibers, resulted in a complete suppression of the multi-unit CHB discharge produced by cisplatin treatment. Single units that were cisplatin sensitive had their activity reduced by either 5-HT3 receptor antagonist treatment or cutting the GDB. Conversely, cisplatin insensitive units were not affected by 5-HT3-antagonism or GDB ablation. The present results indicate that cisplatin activates GI vagal afferent fibers via 5-HT3 receptors but does not affect portal vein/liver vagal afferent fibers, which indicates that intestinal but not hepatic afferent fibers are involved in the toxic effects of cisplatin.
 ...
PMID:Differential effects on gastrointestinal and hepatic vagal afferent fibers in the rat by the anti-cancer agent cisplatin. 1550 8

Nausea and vomiting are significant adverse effects of chemotherapeutic agents like cisplatin, and cause significant patient morbidity. Cisplatin treatment results in oxidant gut injury, which is postulated to be the primary cause of nausea and vomiting. We evaluated the effects of two antioxidant herbs, Scutellaria baicalensis and American ginseng berry, on cisplatin-induced nausea and vomiting using a rat model. Rats react to emetic or nausea-producing stimuli, such as cisplatin, with altered feeding habits, manifested by increased kaolin consumption (pica). We measured pica in rats to quantify cisplatin-induced nausea. We observed that pretreatment of rats with S. baicalensis or ginseng berry extracts resulted in a significant reduction in cisplatin-induced pica. The in vitro free radical scavenging ability of the herbal extract observed in the study, further confirmed the antioxidant action of the herb. We conclude that herbal antioxidants may have a role in attenuating cisplatin-induced nausea and vomiting.
 ...
PMID:Effects of antioxidant herbs on chemotherapy-induced nausea and vomiting in a rat-pica model. 1567 95

Rats lack the emetic reflex but exhibit pica in response to stimuli that induce emesis in species with an emetic reflex, hence it has been proposed that pica may be analogous to emesis in species lacking the reflex. In the present study, we investigated whether pica was present in Suncus murinus (with an emetic reflex) as well as in rats and mice (without emetic reflex) to provide a further insight to the validity of pica as a model for nausea/vomiting. Cisplatin (6 mg/kg, i.p.) induced pica in rats, indicated by a significant increase in kaolin consumption at 24 h (but not 48 h) post-treatment whereas we failed to demonstrate this effect in mice (inbred or outbred strain, 6 or 20 mg/kg i.p.) and whilst cisplatin (20 mg/kg, i.p.) induced emesis in Suncus, kaolin intake was not significantly affected. Furthermore, cisplatin significantly increased the weight of gastric contents at 48 h post-injection in rats and mice indicating delayed gastric emptying whereas this effect was not present in Suncus. These results show that Suncus and two strains of mice, unlike rats, do not develop pica in response to cisplatin which suggests that the consumption of kaolin induced by cisplatin may not be associated with whether or not an emetic reflex is present. The differences in ingestive behaviour and gastric response between species with and without an emetic reflex in response to cisplatin treatment as well as the difference between mice and rats, is discussed in relation to the selection of models for the study of nausea and vomiting.
 ...
PMID:Pica--a model of nausea? Species differences in response to cisplatin. 1593 45


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>