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)

Amplification of the human epidermal growth factor receptor 2 protein (HER2) in primary breast carcinomas has been shown to correlate with poor clinical prognosis for certain patients. Trastuzumab (Herceptin, Genentech, Inc., South San Francisco, California) is a highly purified recombinant DNA-derived humanized monoclonal immunoglobulin G1 kappa antibody that binds with high affinity and specificity to the extracellular domain of the HER2 receptor. In vitro and in vivo preclinical studies have shown that administration of trastuzumab alone or in combination with paclitaxel or carboplatin significantly inhibits the growth of breast tumor-derived cell lines that overexpress the HER2 gene product. At therapeutic doses in breast cancer patients, the mean half-life of trastuzumab is 5.8 days. Trastuzumab serum concentrations reach steady state with mean trough and peak concentrations of 79 microg/mL and 123 microg/mL, respectively. In a 222-patient, single-arm clinical study, treatment with a loading dose of trastuzumab 4 mg/kg administered IV followed by weekly IV doses of 2 mg/kg produced an overall response rate of 14% (2% complete remission and 12% partial remission). The beneficial effects were greatest in patients with the greatest degree (3+) of HER2 protein overexpression. In another clinical study, 469 women with metastatic breast carcinoma were randomized to a paclitaxel or anthracycline-plus-cyclophosphamide regimen with or without trastuzumab. The overall response rate was significantly greater in the trastuzumab-plus-chemotherapy group than in the chemotherapy-alone cohort. The magnitude of observed effects was greatest with pacli taxel plus trastuzumab. The most common adverse effects attributed to trastuzumab in clinical studies were fever and chills, pain, asthenia, nausea, vomiting, increased cough, diarrhea, headache, dyspnea, infection, rhinitis, and insomnia. Trastuzumab in combination with chemotherapy can lead to cardiotoxicity, leukopenia, anemia, diarrhea, abdominal pain, and infection. Trastuzumab has been approved by the US Food and Drug Administration as a single agent for the treatment of patients who have metastatic breast cancer involving overexpression of the HER2 protein and who have received 1 or more chemotherapy regimens; in combination with paclitaxel, it has been approved for the treatment of such patients who have not received chemotherapy.
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PMID:Trastuzumab, a recombinant DNA-derived humanized monoclonal antibody, a novel agent for the treatment of metastatic breast cancer. 1021 34

The recombinant, humanized monoclonal antibody Herceptin is administered as an initial 4 mg/kg i.v. infusion over 90 min, followed by weekly 2 mg/kg i.v. infusions over 30 min. In pivotal clinical trials Herceptin, both as a single agent and in combination with chemotherapy, was found to produce a significant survival benefit in HER2-positive metastatic breast cancer patients. Importantly, Herceptin was well tolerated and was not associated with a poor side-effect profile, producing mainly mild to moderate side-effects. These were generally associated with the initial infusion. The incidence of adverse events was low with Herceptin therapy and severe vomiting and alopecia, typical of many chemotherapy treatment regimens, were not experienced by patients in the trials. Cardiac dysfunction was the most significant Herceptin-related adverse event but could, in most cases, be managed using standard therapy. The favourable adverse event profile seen with Herceptin is reflected in the quality of life (QoL) data. The health-related QoL of patients receiving Herceptin therapy alone or in combination with chemotherapy was found to be maintained. Previous studies have noted a deterioration of health-related QoL in patients treated with chemotherapy only. Thus, as well as providing significant survival benefit, Herceptin therapy improves patient well being.
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PMID:Anti-HER2 therapy: how to use Herceptin in clinical practice. 1284 15

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

Adjuvant cytotoxic chemotherapy following surgical treatment of nonmetastatic breast cancer usually includes an anthracycline. The addition of trastuzumab should be considered for women whose tumours overexpress HER-2 protein. Trastuzumab has been approved in the European Union since 2006 for adjuvant treatment of breast cancer. In 2011, the indications were further specified to allow the use of adjuvant trastuzumab in both anthracycline-based and non-anthracycline protocols. In 2006, the results of the first 3 trials of adjuvant chemotherapy showed an absolute gain in overall survival of about 4% after 4 years with trastuzumab. Updates of these trials, with longer follow-up, along with the results of a fourth trial, confirm the overall survival benefit, whether or not the adjuvant regimen includes an anthracycline (about 91% versus 87%). Trastuzumab carries a risk of NYHA class III or IV congestive heart failure with reduced left ventricular ejection fraction. The risk is higher in patients who receive the doxorubicin + cyclophosphamide combination, one-third of whom have a reduction in left ventricular ejection fraction that persists for several years after the end of treatment. The nature of non-cardiac serious adverse effects depends on whether the protocol includes an anthracycline: anthracycline therapy is associated with more frequent arthralgia, myalgia, hand-foot syndrome, vomiting, leukopenia and neutropenia, while regimens not containing an anthracycline are associated with more anaemia and thrombocytopenia. In practice, in 2012, the addition of trastuzumab to cytotoxic chemotherapy remains a valid option for women who have undergone surgery for nonmetastatic invasive breast tumours that overexpress HER-2 protein. It remains to be shown whether anthracycline-free chemotherapy regimens, which are less cardiotoxic, are equally effective.
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PMID:Adjuvant trastuzumab for breast cancer. A second look. Longer follow-up confirms improved overall survival. 2337 91

A meta-analysis was performed to examine the efficiency and safety of trastuzumab in patients with advanced gastric and gastroesophageal cancer (AGC). By searching multiple databases from 1990 to March 2016, all randomized controlled trials (RCTs) which compared the effect of trastuzumab-combined chemotherapy (TC) versus chemotherapy alone (CT) in gastric cancer would be included. Five RCTs with a total of 875 patients were included. Trastuzumab can improve the overall survival (OS) rate, progression-free survival (PFS), one-year survival rate, two-year survival rate and overall response rate (ORR) of patients with AGC. There were no difference between the two arms in terms of grade 3/4 adverse effects, such as vomiting, nausea, neutropenia, thrombocytopaenia and anemia. Diarrhea increased in TC group. Trastuzumab can significantly improve the survival rate, PFS, ORR of patients with AGC. It is safe and feasible and can be tolerated. It needs further prospective multinational multicenter RCTs with large samples to define the clinical benefits of trastuzumab.
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PMID:The efficiency and safety of trastuzumab for advanced gastric and gastroesophageal cancer: a meta-analysis of five randomized controlled trials. 2792 77