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)

The development of an oral formulation of vinorelbine (Navelbine softgelatine capsules, Pierre Fabre Pharma, Freiburg i.Br., Germany) represents a significant advance in the treatment of patients with cancer. Oral chemotherapy is more convenient for the patients and brings significant time savings. Vinorelbine is rapidly absorbed after oral ingestion. The bioavailability is in the range of 33 to 43% and is not affected by concomitant food intake or by vomiting occuring 1.5 h or later after dosing. No significant differences in the pharmacokinetics of oral vinorelbine were observed between elderly (> or =70 years) and younger patients. The recommended dose schedule for oral vinorelbine is 60 mg/m(2) weekly for the initial 3 weeks (cycle 1) and 80 mg/m(2) weekly thereafter. However, if severe neutropenia is encountered during the first cycle, treatment is continued with weekly doses of 60 mg/m(2). Bioavailability studies have demonstrated that oral vinorelbine doses of 60 and 80 mg/m(2) are comparable to intravenous doses of 25 and 30 mg/m(2), respectively. Several clinical studies have demonstrated that the new oral formulation of vinorelbine can be safely administered, even to elderly patients, and is comparable in activity to intravenous vinorelbine in advanced non-small cell lung cancer (NSCLC) and metastatic breast cancer (MBC). A randomized phase II comparison of oral vinorelbine at the recommended dose schedule vs. intravenous vinorelbine at 30 mg/(2) in patients with advanced NSCLC found no significant differences in response rate, progression-free and overall survival between the two treatments. In studies of combination chemotherapy using vinorelbine plus cisplatin or carboplatin in advanced NSCLC, or vinorelbine plus taxanes, capecitabine,epirubicin, or the monoclonal HER2/neu antibody trastuzumab in MBC, intravenous vinorelbine could be completely or partially replaced by oral vinorelbine, resulting in maintained efficacy, good tolerability and improved patient convenience. Concurrent chemoradiation with oral vinorelbine and cisplatin was shown to be well tolerated and produced significant down-staging in patients with locally advanced NSCLC. Metronomic chemotherapy is a new treatment approach designed to maximize the antiangiogenic effect. Oral vinorelbine given every other day at low doses is currently evaluated in patients with refractory solid tumors. Oral vinorelbine has also proven useful as a substitute for intravenous vinorelbine in patients experiencing intractable acute tumor pain during or after intravenous infusion of vinorelbine.
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PMID:[Oral vinorelbine: pharmacology and treatment outcome in non-small cell bronchial carcinoma and breast carcinoma]. 1653 41

Our objectives were to assess the efficacy and toxicity of gemcitabine plus cisplatin as first-line therapy in metastatic breast cancer (MBC). Patients with stage IV MBC and no prior chemotherapy for metastatic disease were treated with gemcitabine 1200 mg/m on days 1 and 8, and cisplatin 75 mg/m on day 1 every 21 days. Up to 6 cycles were given. A total of 46 patients with a median age of 49 years (range 24-77) and Karnofsky performance status of 80 or above were enrolled. In total, 238 cycles were administered. Of the 42 patients evaluable for response, seven (17%) achieved a complete response and 27 (64%) a partial response, for an overall response rate of 81% [95% confidence interval (CI) 69-93%]. Median time to progression was 14.9 months (95% CI 0-30.2 months). Median duration of response was 24.2 months (95% CI 11.2-37.3 months). The median survival was 27.9 months (95% CI 23.1-32.7 months), and the 1- and 2-year survival probabilities were 71.4 and 61.4%, respectively. All patients were evaluable for toxicity, and grade 3/4 WHO toxicities included neutropenia (41.3%), anemia (8.7%), thrombocytopenia (8.7%), alopecia (26.1%) and nausea/vomiting (32.6%). We conclude that gemcitabine plus cisplatin is a highly effective and safe first-line treatment for patients with MBC. The time to progression of 14.9 months compares favorably with other standard treatments (anthracyclines, taxanes). A randomized study is required to further investigate the role of this combination as first-line treatment for MBC.
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PMID:Phase II study of gemcitabine plus cisplatin in metastatic breast cancer. 1670 14

Cytotoxic agents such as anthracycline or taxanes have provided a good clinical response for breast cancer patients, although they have failed to prolong the survival rate and to improve the quality of life (QOL) of these patients. On the other hand, cytostatic agents such as 5-fluorouracil (5-FU) have to be focused to accommodate a long term progression with respect to efficacy and the patients' QOL improvement. S-1 was a newly developed and orally administered fluorinated pyrimidine containing 1 M tegafur (FT) and two classes of a modulator, 5-chloro-2,4-dihydroxypyrimidine (CDHP) and potassium oxonate (Oxo) at a molar ratio of FT : CDHP : Oxo= 1 : 0.4 : 1. Specific dose limiting factors such as neutropenia, diarrhea and stomatitis have been observed in a previous phase I study. Two phase II studies of 4 weeks treatment of S-1 (1 M tegafur-0.4 M gimestat-1 M otastat potassium) for the advanced or metastatic breast cancer patients were carried out in Japan. Among 108 evaluable patients for response, there were 10 complete response (CR) and 35 partial response (PR) with an overall response rate of 41.7% (95% confidence interval, 32.3-51.5%). The incidence of toxicity (> or = grade 3) was as followed: neutropenia 9.3%, anemia 0.9%, stomatitis 1.9% and nausea/vomiting 0.9%. The median follow-up period for patients was 802 days. S-1 will be the new promising oral agent like a capecitabine which has been widely used as a third-line chemotherapy for the heavily treated breast cancer patients.
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PMID:[Clinical benefit of S-1 in metastatic breast cancer]. 1689 3

The aim of the study was to obtain United Kingdom-based societal preferences for distinct stages of metastatic breast cancer (MBC) and six common toxicities. Health states were developed based on literature review, iterative cycles of interviews and a focus group with clinical experts. They described the burden of progressive, responding and stable disease on treatment; and also febrile neutropenia, stomatitis; diarrhoea/vomiting; fatigue; hand-foot syndrome (grade 3/4 toxicities) and hair loss. One hundred members of the general public rated them using standard gamble to determine health state utility. Data were analysed with a mixed model analysis. The study sample was a good match to the general public of England and Wales by demographics and current quality of life. Stable disease on treatment had a utility value of 0.72, with a corresponding gain of +0.07 following a treatment response and a decline by 0.27 for disease progression. Toxicities lead to declines in utility between 0.10 (diarrhoea/vomiting) and 0.15 (febrile neutropenia). This study underlines the value that society place on the avoidance of disease progression and severe side effects in MBC. This may be the largest preference study in breast cancer designed to survey a representative general public sample.
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PMID:Health state utilities for metastatic breast cancer. 1696 55

Rebeccamycin analog (NSC 655649) is a synthetic antibiotic cytotoxic agent thought to inhibit topoisomerase function. We sought to determine the response rate to rebeccamycin analog among patients with refractory advanced breast cancer using two different treatment schedules. Eligible patients had measurable disease, central venous access, and one or two prior chemotherapy regimens for advanced cancer, or recurrence within 12 months of adjuvant chemotherapy. Patients were randomized to rebeccamycin analog on one of two treatment schedules: arm 1, 500 mg/m2 IV bolus every 21 days; arm 2, 140 mg/m2 IV bolus daily x 5 days, every 21 days. The primary study endpoint was response rate; a two stage accrual design evaluated each schedule separately. Forty-two women entered the trial, 21 on each arm. Prior chemotherapy regimens for metastatic breast cancer were: 0, n=4; 1, n=21; 2, n=17. Prior treatments (including adjuvant therapy) anthracyclines: 88%, taxanes 67%, 5FU-based therapy, 50%. There were 5 partial responses (overall response rate 12%), two in arm 1 and 3 in arm 2, all in patients with prior anthracycline-based adjuvant chemotherapy. Median time to progression was 2.1 months (range 1-14+ months). An additional 9 patients had stable disease as best response. Grade 3 or 4 toxicity rates were: anemia 5%, neutropenia 33%, thrombocytopenia 12%, RBC transfusion 14%, nausea/vomiting 10%. Toxicity profiles were similar between the treatment arms. Rebeccamycin analog is reasonably well tolerated on two different treatment schedules for advanced breast cancer, with modest clinical activity in this heavily pretreated population.
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PMID:Rebeccamycin analog for refractory breast cancer: a randomized phase II trial of dosing schedules. 1696 7

The purpose of this study was to investigate the safety, pharmacokinetics and preliminary efficacy of bivatuzumab mertansine in patients with CD44v6-positive metastatic breast cancer. Anthracycline and taxane-pretreated patients with metastatic breast cancer that expressed CD44v6 received one single infusion of bivatuzumab mertansine and were observed for 21 days within one treatment course. Starting dose was 25 mg/m, while dose was escalated by increments of 25 mg/m. Patients who experienced a disease stabilization were eligible for further courses with bivatuzumab mertansine. Blood serum samples were taken throughout the treatment period for pharmacokinetic analysis. Twenty-four patients were treated at eight different dose levels (25-200 mg/m), seven of these patients received more than one course of bivatuzumab mertansine. Two dose-limiting toxicities occurred: one patient treated with 125 mg/m developed transient National Cancer Institute Common Toxicity Criteria grade 4 elevation of liver enzymes; another patient treated at 175 mg/m experienced National Cancer Institute Common Toxicity Criteria grade 3 vomiting. She died from renal failure, which might have been caused by deterioration of pre-existing renal insufficiency. The most common toxicities were transient and mild skin disorders in 75% of patients. As a consequence of one fatal toxic epidermal necrolysis that occurred in a study running in parallel, the clinical trials programme of bivatuzumab mertansine was discontinued. None of the patients developed antibodies against bivatuzumab mertansine. No objective responses were observed. Disease stabilization was achieved in 50% of patients independently of dose level. In conclusion, bivatuzumab mertansine targets CD44v6 and appears to stabilize heavily pretreated metastatic breast cancer that expresses CD44v6. The maximum tolerated dose could not be determined in this trial as the sponsor discontinued the clinical development of bivatuzumab mertansine.
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PMID:Safety and pharmacokinetics of bivatuzumab mertansine in patients with CD44v6-positive metastatic breast cancer: final results of a phase I study. 1735 1

To summarise the advances in the hormonal treatment of post-menopausal metastatic breast cancer, this paper reviews the published literature regarding the randomised trials comparing aromatase inhibitors (AIs) versus tamoxifen as a first-line therapeutic choice, or AIs versus megestrole acetate (MEG) as a second-line option. The pooled analysis of these authors on AI versus MEG as a second-line option for post-menopausal metastatic breast cancer suggested that AIs do not add any significant benefit over MEG in terms of overall response rate (ORR) and time to progression. According to the Cochrane Database, use of an AI as a second-line therapy versus any other endocrine therapy (mostly MEG) has shown a significant benefit in terms of overall survival, but not for progression-free survival, clinical benefit (CB) or ORR. Concerning the authors' comparisons between AIs versus tamoxifen as a first-line endocrine option in post-menopausal women with metastatic breast carcinoma, AIs seem to be superior to tamoxifen, with a significant benefit in terms of ORR, CB and time to progression being observed in favour of AIs over tamoxifen with fixed effects estimates. According to the Cochrane Database, there was an advantage to the use of AIs over tamoxifen in terms of progression-free survival and CB, but not for overall survival or ORR. With regards to toxicity, AIs show similar levels of hot flushes and arthralgia, increased risks of nausea, diarrhoea and vomiting, but a decreased risk of vaginal bleeding and thromboembolic events compared with other endocrine therapies. Weight gain, dyspnoea and peripheral oedema seem to be more frequent with MEG. At present, there is no proved overall survival difference in patients who are treated first with an AI and then with tamoxifen compared with the opposite sequence. In the metastatic setting, results are limited and are based on retrospective analyses.
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PMID:Aromatase inhibitors in post-menopausal metastatic breast carcinoma. 1759 87

The aim of this randomized phase II study was to evaluate the anti-tumor activity and safety of capecitabine and vinorelbine in patients with metastatic breast cancer pretreated with taxanes and anthracyclines. We planned to randomize 72 patients to capecitabine 1250 mg/m(2) orally bid days 1-14 or vinorelbine 30 mg/m(2) i.v. days 1 and 8, both given every 3 weeks. The study was stopped due to poor accrual with 47 patients enrolled. Responses were seen in 2/23 patients treated with capecitabine (8.7%; 95% CI 1.1-29.0) and 3/24 patients treated with vinorelbine (12.5%; 95% CI 2.7-32.4). Median progression-free survival was 2.8 and 2.6 months, and median overall survival was 9.3 and 11.0 months, in the capecitabine and vinorelbine arms, respectively. There was more hematologic toxicity, neurotoxicity, and nausea/vomiting with vinorelbine and more diarrhea and hand-foot syndrome with capecitabine. The anti-tumor activity of capecitabine and vinorelbine seems to be comparable, but the toxicity profiles are different.
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PMID:Anti-tumor activity of capecitabine and vinorelbine in patients with anthracycline- and taxane-pretreated metastatic breast cancer: findings from the EORTC 10001 randomized phase II trial. 1797 88

Trastuzumab is a recombinant humanised monoclonal antibody specific for the growth factor receptor p185(HER2) (HER2) which is overexpressed in 25 to 30% of breast cancer tumours. The drug inhibits the growth of human breast cancer cells overexpressing HER2 in vitro and in vivo. It shows additive antitumour activity in vitro and in vivo when administered with paclitaxel, doxorubicin, various cytokines or tamoxifen. In patients with metastatic breast cancer whose tumours overexpressed HER2, trastuzumab (4 mg/kg loading dose then 2 mg/kg/week by intravenous infusion) produced objective responses in 21% of 213 patients. A further 7% of patients had minor responses and 30% had stable disease. Combination therapy with trastuzumab and either paclitaxel or doxorubicin (or epirubicin) plus cyclophosphamide produced a higher response rate (49%), longer median time to disease progression (7.6 months), a higher one-year survival rate (78%) and significantly increased median overall survival (25.4 months) than antineoplastic agents alone (response rate 32%, time to disease progression 4.6 months, one-year survival rate 67% and overall survival 20.3 months) in a phase III study in 469 patients. Trastuzumab is generally well tolerated. Chills, fever, nausea, vomiting, weakness and headache were among the most common adverse events in clinical trials and occurred in 40 to 50% of patients during the first infusion of the drug. Cardiac dysfunction was the most serious adverse event reported and was more common in patients receiving trastuzumab plus antineoplastic therapy than in those receiving trastuzumab alone.
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PMID:Trastuzumab. 1803 Nov 72

Anthracyclines and taxanes are among the most active substances used in the treatment of metastatic breast cancer (MBC). Their frequent use in the adjuvant setting and in cumulative toxicities including cardiotoxicity, however, often limit their use in MBC. The trend towards the use of adjuvant trastuzumab-containing regimens, which can also produce cardiotoxicity, adds further support to the need for effective agents with improved tolerability in the metastatic setting. Pegylated liposomal doxorubicin (PLD) can be an effective alternative to conventional anthracyclines for certain women with MBC. In phase III clinical trials, PLD was as effective as doxorubicin and produced significantly less cardiotoxicity in women with MBC. The incidences of myelotoxicity, nausea/vomiting, and alopecia were also lower with PLD, whereas hand-foot syndrome and stomatitis occurred more frequently. Phase II and III trials conducted in women with MBC support the use of PLD monotherapy in patients relapsing after adjuvant anthracycline-containing therapy, in heavily pretreated patients with taxane-refractory disease, in patients with cardiovascular risk factors (e.g. hypertension and mediastinal irradiation), in elderly patients, and in patients for whom specific acute doxorubicin toxicities, such as alopecia, are particularly worrying.
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PMID:Single-agent treatment with pegylated liposomal doxorubicin for metastatic breast cancer. 1804 24


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