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)

Buprenorphine is a potent opioid available as a transdermal delivery system (TDS) formulation. This open-label study investigated its safety, tolerability, and efficacy in 30 patients with chronic painful neuropathy. Subjects with visual analogue scale (VAS) score > or = 5 under stable analgesic treatment were entered. The starting dosage of 35 microg/h was increased up to 70.0 microg/h in case of unsatisfactory pain control as assessed by fortnightly visits. The primary endpoint was the number of patients achieving at least 30% pain relief at day 42 visit. Treatment was safe over the study period. Nine patients dropped out for side effects, mostly nausea and daily sleepiness. Buprenorphine TDS was well tolerated in 21 patients. Thirteen patients achieved > 30% of pain relief at day 42 visit. Five patients needed to increase the dosage to 52.5 microg/h. Eight patients did not meet the primary outcome, but none allowed increasing the dosage to 70 microg/h, and four patients withdrew consent to continue the study before day 42 visit because of a 'fear to become addicted,' although 40% had obtained VAS reduction. In our study, which needs to be confirmed by a controlled trial, buprenorphine TDS induced clinically meaningful pain relief in about 40% of patients with chronic painful neuropathy, suggesting its use as a third-line treatment.
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PMID:Short- and intermediate-term efficacy of buprenorphine TDS in chronic painful neuropathies. 1919 68

Platinum-based chemotherapeutic doublets have produced significant survival benefits for patients with non-small cell lung cancer of all disease stages. The optimal combination of chemotherapy has been the subject of much investigation, and the ideal platinum agent the subject of ongoing and heated debate. For patients with resected disease, all evidence of survival advantage rests with cisplatin, and the only clinical trial to evaluate carboplatin-based therapy failed to show a survival benefit. In the setting of locally advanced lung cancer, no comparative data exist, and even randomized phase III trials are largely lacking. Cisplatin-based doublets provide the most consistent evidence of superior survival when coupled with definitive thoracic radiation. Meta-analyses of palliative chemotherapy indicate consistent survival advantages with cisplatin-based therapy over carboplatin; however, the relative advantage is small. Cisplatin carries a higher toxicity profile, including nausea, vomiting, neuropathy, renal insufficiency, and alopecia in comparison to carboplatin. When the goal of therapy is curative, the survival benefits with cisplatin are in most circumstances worth the increased toxicities. When the goal of therapy is palliation, the relative price of toxicity needs to be weighed on the basis of the individual patient in an effort to maximize quality of life.
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PMID:Cisplatin versus carboplatin in NSCLC: is there one "best" answer? 1922 91

Objectives of this study were to determine the maximum tolerated dose and to characterize the side effect profile and pharmacokinetics of lenalidomide in patients with advanced refractory solid tumors. Patients were treated on a modified Fibronacci dose escalation scheme with an oral daily dose of lenalidomide. A total of 45 patients with 8 different tumor types were accrued. Doses administered included 5, 10, and 20 mg continuous daily doses, every 28 days (n = 15), later modified to intermittent doses of 15, 20, 25, 30, 35, and 40 mg, with a 21 days-on and 7 days-off schedule, due to observed side effects. Lenalidomide exhibited a linear pharmacokinetics over a wide range of doses with the mean half-life of 3.9 hours. The renal function affected lenalidomide clearance, resulting in 50% reduction in patients with mild renal impairment compared with patients with normal function (CL/F = 243 mL/min). Stable disease was documented in 12 of 44 evaluable patients, of whom 9 patients had prostate cancer. Most frequent grade 1 and 2 toxicities included fatigue, nausea, pruritus/rash, neutropenia, and neuropathy. Grade 3/4 events were predominantly hematologic. Lenalidomide was well tolerated up to a 35-mg/d intermittent dosing schedule at doses higher than previously indicated for hematologic malignancies.
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PMID:Phase I study of oral lenalidomide in patients with refractory metastatic cancer. 1945 3

PURPOSE Ixabepilone (BMS-247550) is a microtubule-stabilizing epothilone B analog with activity in taxane-resistant metastatic breast cancer. The Gynecologic Oncology Group conducted a phase II evaluation of the efficacy and safety of ixabepilone in patients with recurrent or persistent platinum- and taxane-resistant primary ovarian or peritoneal carcinoma. PATIENTS AND METHODS Patients with measurable platinum- and taxane-resistant ovarian or peritoneal carcinoma, defined as progression during or within 6 months of one prior course of treatment with each agent, received intravenous ixabepilone 20 mg/m(2) administered over 1 hour on days 1, 8, and 15 of a 28-day cycle. Results Of 51 patients entered, 49 were eligible. The objective response rate was 14.3% (95% CI, 5.9% to 27.2%), with three complete and four partial responses. Twenty patients (40.8%) had stable disease, whereas sixteen (32.7%) had increasing disease. The median time to progression was 4.4 months (95% CI, 0.8 to 32.6+ months); median survival was 14.8 months (95% CI, 0.8 to 50.0) months. Patients received a median of two treatment cycles (range, 1 to 29 cycles), and 18.4% of patients received > or = six cycles. Adverse effects included peripheral grade 2 (28.5%) and grade 3 (6.1%) neuropathy, grades 3 to 4 neutropenia (20.4%), grade 3 fatigue (14.3%), grade 3 nausea/emesis (22%), grade 3 diarrhea (10%), and grade 3 mucositis (4%). CONCLUSION Ixabepilone 20 mg/m(2) over 1 hour on days 1, 8, and 15 of a 28-day cycle demonstrates antitumor activity and acceptable safety in patients with platinum- and taxane-resistant recurrent or persistent ovarian or primary peritoneal carcinoma.
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PMID:Phase II clinical trial of ixabepilone in patients with recurrent or persistent platinum- and taxane-resistant ovarian or primary peritoneal cancer: a gynecologic oncology group study. 1991 61

The epothilone B analogue, ixabepilone, binds to b-tubulin, is effective for taxane-refractory metastatic breast cancer (MBC), and may be given every 3 weeks or weekly. We evaluated the efficacy of weekly ixabepilone (I) plus trastuzumab (T) and carboplatin (C) as first line therapy in HER2 + MBC. Patients with HER2+ (3+ by IHC or FISH amplified) MBC received I (15 mg/m2 IV) and C (area under the curve, AUC = 2 IV) on days 1, 8, and 15 of a 28-day cycle for a maximum of 6 cycles, plus weekly T (4 mg/kg loading dose then 2 mg/kg IV) during chemotherapy then every 3 weeks (6 mg/kg IV) until disease progression. The primary objective was to determine whether the combination was associated with a response rate (RR) of at least 75%. Fifty-nine patients were treated, and 39 had HER2 overexpression confirmed in a central lab (cHER2+). For all treated patients, objective response occurred in 26 patients (44%; 95% CI 31-58%), median time to progression was 8.2 months (95% CI 6.3-9.9), and median overall survival was 34.7 months (95% CI 25.7 to [not reached]). Results were comparable for cHer2? cancers. Grade 3-4 adverse events included neutropenia (49%), thrombocytopenia (14%), fatigue (12%), nausea (7%), diarrhea (7%), and neuropathy (7%). One patient died from treatment complications during cycle 1. Weekly ixabepilone and carboplatin plus trastuzumab have an acceptable toxicity profile, but are not likely to be associated with an RR of 75% in HER2+ MBC. Efficacy appears comparable to paclitaxel, carboplatin, and trastuzumab.
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PMID:A phase II trial of trastuzumab plus weekly ixabepilone and carboplatin in patients with HER2-positive metastatic breast cancer: an Eastern Cooperative Oncology Group Trial. 2001 54

Breast cancer treatment currently requires the joint efforts of a multidisciplinary team to effectively combine chemotherapy, hormone therapy, biological agents, surgery and radiation therapy when needed. To develop such a treatment plan, it is important to know the benefits as well as the potential toxic effects of each therapy. Thus, many patients with early breast cancer complain of collateral adverse events such as fatigue, nausea, vomiting, loss of libido, hot flashes, night sweats or neuropathy due to the complex therapies they are receiving. To date, the treatment of such symptoms is an important issue that greatly affects the quality of life of these patients. In this review, we report the content of a multi-expert meeting where the incidence of and medical approach to some of the most common adverse events encountered during the treatment of patients with early breast cancer were analysed.
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PMID:Supportive care for patients with early breast cancer. 2008 Apr 69

South Africa has a very high HIV disease burden and proper patient adherence to anti-retroviral therapy (ART) is crucial in achieving optimal treatment outcomes. Factors influencing adherence include demographic and psychosocial factors, medication-related issues and other patient-related matters. This study was carried out in order to determine factors associated with poor compliance to anti-retroviral (ARV) medications in a rural setting. This interview-based descriptive and analytical study was carried out in a health centre where 168 patients who received ARVs were interviewed with pre-structured questionnaires, which covered various important compliance-related aspects. The results showed that 37.5% of the patients were non-adherent. Amongst men, poor adherence was seen in those who were single (48.9%), with tertiary education (60%), in those who consumed alcohol regularly (47.1%) and in those who were unemployed (56.1%). Higher rates of non-adherence in women was associated with being single (36.5%) and in those who used alcohol (60.7%). Medication-related adverse effects were reported in 47% of patients, notably, neuropathy, headache, nausea, loss of memory, diarrhoea and fatigue. Common reasons for missing doses were: being away from home (57.1%), simply forgot (41.3%), side effects (50.8%) and being too busy (49.2%). Poor adherence to ART is an important concern relating to HIV management in our setting and needs to be addressed with more patient-oriented interventions.
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PMID:Factors associated with poor adherence to anti-retroviral therapy in patients attending a rural health centre in South Africa. 2046 69

The use of bortezomib in combination with other desensitization therapies like plasmapheresis, IVIG, and rituximab has allowed the decrease of antibody levels during treatment in some patients. However, all patients described here have experienced rebound effects to the same or higher levels than the ones before therapy was started. Unfortunately, no donors became available to some of these patients when their antibodies were at lower levels. Three out of the four patients presented had adverse reactions to bortezomib which include nausea, vomiting, diarrhea, myalgias and severe neuropathy. In one patient (pre-heart transplant patient #1) we noticed that some clones were selectively more susceptible to the treatment with bortezomib than others. We will continue antibody monitoring in this patient and hopefully the possibility is there, even though the overall PRA is not reduced, that certain clones will be affected and no longer produced antibody allowing these patients a wider selection of acceptable donors.
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PMID:Desensitization protocol using bortezomib for highly sensitized patients awaiting heart or lung transplants. 2052 4

Taxane and platinum drugs are important agents in the treatment of cancer and have shown activity against a variety of tumors, including ovarian, breast, and lung cancer, either as single agents or in combination with other chemotherapy drugs. However, a serious and prevalent side effect of taxane (docetaxel and all formulations/derivatives of paclitaxel) and platinum (cisplatin, carboplatin, and oxaliplatin) agents is dose-limiting chemotherapy-induced peripheral neuropathy (CIPN). CIPN can result in treatment delays, dose modifications, and, in severe cases, discontinuation of chemotherapy. Consequently, effective treatments for CIPN are needed. Dimesna (BNP7787; Tavocept; disodium 2,2'-dithio-bis-ethanesulfonate) is an investigational drug that is undergoing international clinical development as a treatment that is coadministered with first-line taxane and platinum combination chemotherapy in patients with inoperable advanced primary adenocarcinoma of the lung. BNP7787 is currently being developed with the objective of increasing the survival of cancer patients receiving taxane- and/or cisplatin-based chemotherapy. Additional data indicate that BNP7787 may also protect against common and serious chemotherapy-induced toxicities, including chemotherapy-induced anemia, nausea, emesis, nephrotoxicity, and neuropathy, without interfering with antitumor activity of the chemotherapeutic agent(s). Studies herein show that BNP7787 prevents aberrant microtubule protein (MTP) polymerization that is caused by exposure of MTP to paclitaxel or cisplatin. BNP7787 modulates paclitaxel-induced hyperpolymerization of MTP in a dose-dependent manner, and mesna, an in vivo metabolite of BNP7787, protects against time-dependent cisplatin-induced inactivation of MTP. We propose that interactions between BNP7787 and MTP may play a role in BNP7787-mediated protection against CIPN.
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PMID:BNP7787-mediated modulation of paclitaxel- and cisplatin-induced aberrant microtubule protein polymerization in vitro. 2080 79

The primary aim of this phase 1 study was to determine the maximum tolerated dose (MTD) and evaluate the safety of nifurtimox alone and in combination with cyclophosphamide and topotecan in multiple relapsed/refractory neuroblastoma pediatric patients. The secondary aim was to evaluate the pharmacokinetics of nifurtimox and the treatment response. To these ends, we performed a phase 1 dose escalation trial of daily oral nifurtimox with toxicity monitoring to determine the MTD, followed by 3 cycles of nifurtimox in combination with cyclophosphamide and topotecan. Samples were collected to determine the pharmacokinetic parameters maximum concentration, time at which maximum concentration is reached, and area under the curve between 0 and 8 hours. Treatment response was evaluated by radiographic and radionuclide (I-metaiodobenzylguanidine) imaging, measurement of urinary catecholamines, and clearance of bone marrow disease. We determined the MTD of nifurtimox to be 30 mg/kg/d. The non-dose-limiting toxicities were mainly nausea and neuropathy. The dose-limiting toxicities of 2 patients at 40 mg/kg/d were a grade 3 pulmonary hemorrhage and a grade 3 neuropathy (reversible). Overall, nifurtimox was well tolerated by pediatric patients at a dose of 30 mg/kg/d, and tumor responses were seen both as a single agent and in combination with chemotherapy. A Phase 2 study to determine the antitumor efficacy of nifurtimox is currently underway.
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PMID:A phase 1 study of nifurtimox in patients with relapsed/refractory neuroblastoma. 2106 21


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