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 toxicity and clinical response to treatment with the combination of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) in patients with metastatic melanoma was evaluated. From May 1993 through February 1994, 20 patients were treated with 24 courses of IFN-gamma with or without IL-2. A 7-day course of subcutaneous IFN-gamma alone was administered to cohorts of two or three patients each at doses of 0.1, 0.2, or 0.3 mg/m2. Thirteen patients received escalating doses of IFN-gamma between 0.2 and 0.5 mg/m2 followed by the intravenous (i.v.) administration of IL-2 (720,000 IU/kg) given three times a day. A treatment course consisted of two cycles (maximum of 15 doses of IL-2 per cycle) separated by a 10-day interval. Five additional patients were treated with five courses of IFN-gamma, IL-2, and tumor-infiltrating lymphocytes (TILs). All patients treated had the diagnosis of metastatic melanoma. The maximal tolerated dose of subcutaneous IFN-gamma was established at 0.3 mg/m2 with dose-limiting hepatotoxicity. Immunohistochemistry analyses showed detectable upregulation of MHC class I alleles in one (8%) of 12 patients. Two of 20 patients who received the combination of IFN-gamma and IL-2 had responses, one partial and one complete response. The duration of response was 7 months for the partial response and 12 months for the complete response. IFN-gamma was tolerated with minimal side effects of nausea, vomiting, malaise, and decreased hematopoiesis. No increased toxicities were found with the combination treatment, as compared with IL-2 alone. One death occurred on the third day of treatment with IFN-gamma alone from hemorrhage into brain metastases. There were no responders in the five patients who received the combination treatment of TIL, IL-2, and IFN-gamma. From these findings, we conclude that further studies looking at this combination treatment are not warranted.
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PMID:Combination therapy with interferon-gamma and interleukin-2 for the treatment of metastatic melanoma. 885 24

Forty-three patients with either limited or extensive small cell lung carcinoma were treated with either etoposide and cisplatin (EP) regimen or EP alternating with cyclophosphamide, doxorubicin and vincristine. Patients with limited disease were consolidated with radiotherapy. Responses were 96% (44% complete response) and 71% (6% complete response) in the patients with limited and extensive diseases, respectively. The 2-year disease-free and overall survival in the limited disease patients were 19% and 27%, respectively. None of the patients with extensive disease survived beyond 2 years. Toxicity of the therapy was acceptable. Forty percent developed grade 2 vomiting. Two patients had neutropenic fever of which one was fatal. One of the two-year survivors developed a second malignancy (oesophageal carcinoma). Despite consolidative radiotherapy in all responding patients with limited disease, 73% of the failure included a locoregional component. In the entire group, one-third of the patients developed brain metastases. Hence, more effective drugs and local treatment modalities are needed to improve this result.
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PMID:Treatment of small cell lung cancer: a single institutional experience. 889 24

Brain metastases represent a common complication of breast and lung cancer, with an overall incidence exceeding 30-40% of cases. Results achieved with radiotherapy are disappointing, with a median survival of a few months, and no clear activity has been observed with chemotherapy. The aims of this study were to assess the activity and feasibility of a new chemotherapeutic approach according to the following schedule: lomustine, 80 mg/m2 day 1; carboplatin, 80 mg/m2 days 1, 8, 15, 22; vinorelbine, 20 mg/m2 days 1, 8, 15, 22; L-leucovorin 250 mg/m2 days 1, 8, 15, 22; and fluorouracil, 500 mg/m2 days 1, 8, 15, 22. Cycles were repeated every 6 weeks. Since January 1994, 28 patients have been enrolled and 26 are evaluable for response and side effects. Major patient characteristics were median age, 55 years (range 31-72); men/women 15/11; lung primary, 20; breast primary, 6; performance status Eastern Cooperative Oncology Group, 0-2. A total of 64 cycles were administered (median/patient, two cycles). Nine partial remissions have been observed (35%, 95% confidence interval 17-56%), 6 disease stabilizations, and 11 disease progressions. Median duration of response was 3 months, and median time to progression for the whole group was 3.7 months (range 1-7). Treatment was well tolerated. Mild or moderate side effects included neutropenia, thrombocytopenia, mucositis, and nausea/vomiting; grade III-IV toxicity included neutropenia and thrombocytopenia. In conclusion, our results indicate that the schedule proposed is feasible and effective in this subset of patients.
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PMID:Activity of combination chemotherapy in brain metastases from breast and lung adenocarcinoma. 916 59

Interleukin (IL) 2 plays an important role in enhancing the immune response, whereas IL-4 has pluripotent activities which include affecting immune function. Preclinical data suggest that the combination might have enhanced immunomodulatory activity. In this Phase I trial in patients with advanced solid tumors, both IL-2 and IL-4 were given by separate s.c. injections simultaneously daily, 5 days in a row, Monday through Friday, for 3 consecutive weeks, followed by a 1-week break from treatment. Cycles could be repeated. The dose of IL-2 was kept constant at 9 x 10(6) IU/m2/injection while the dose of IL-4 was escalated beginning at 100 microgram/m2/injection and increasing by 100-microgram/m2 increments to a planned level of 400 microgram/m2/injection. Sixteen patients were entered in this study, with one patient being ineligible because of the presence of brain metastases. Of the 15 eligible patients, there were 14 males and 1 female, with a median age of 54 (range, 38-67) years and initial performance status of 0 in 5 patients and 1 in 10 patients. Patients were treated at levels of up to 300 microgram/m2/injection of IL-4 before the study was closed due to withdrawal of the drug by the manufacturer. The most commonly observed toxicities were fatigue, fever and chills, local reaction, nausea/vomiting and anorexia, headache and nasal stuffiness, and coughing, sometimes with the production of clear white sputum, more common in smokers. Duodenal ulcers occurred in one patient and one patient had grade 4 cardiac toxicity consisting of an asymptomatic minimal elevation of the creatinine phosphokinase MB isoenzyme (CPK-MB). Grade 3 hyponatremia occurred in two patients, and elevated liver function tests and creatinine occurred but were not dose limiting. Eosinophilia of unknown significance occurred in all patients. There were statistically significant elevations in absolute numbers of most T-cell subsets examined, without changes in circulating B cells. No antibodies to the IL-4 were found after one cycle. One patient with renal cell carcinoma showed a significant decrease in tumor burden after one cycle of treatment. Because of the IL-4 withdrawal, the maximum tolerated dose for this combination of drugs given by the route and schedule used here was not determined and will require additional testing. Subcutaneous IL-2 and IL-4 given simultaneously show important immunomodulatory and antitumor effects and should be tested further in cancer patients.
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PMID:Phase I trial of simultaneous administration of interleukin 2 and interleukin 4 subcutaneously. 981 6

Inspired by the high response rates achieved with the DBCT regimen (dacarbazine [DTIC], carmustine [BCNU], cisplatin and tamoxifen [TAM]), we administered the nitrosourea compound fotemustine, cisplatin and TAM (FCT regimen) to 69 patients with metastatic melanoma. Fotemustine (100 mg/m2) and cisplatin (100 mg/m2) were administered every 4 weeks, preceded by TAM 160 mg daily for 7 days from the second course onwards. Pharmacokinetic blood sampling was performed in 14 patients during the initial two cycles to compare the pharmacokinetic behaviour of fotemustine with or without TAM. Previous chemo- or radiotherapy was allowed, and patients with brain metastases or concomitant other malignancies were included. Four complete and 11 partial responders were observed among 66 evaluable patients, yielding a response rate of 22.7% (95% confidence interval 12.9 32.5%). The median survival time was 6.4 months (range 0.1-52+ months). The main toxicities were thrombocytopenia, protracted nausea/vomiting and ototoxicity. Renal toxicity was generally mild, but possibly contributed to two deaths. Seven patients experienced deep venous thrombosis during the study. TAM had no influence on the pharmacokinetics of fotemustine. The activity of the FCT regimen was clearly inferior to that initially reported with DBCT treatment. However, a recent publication concludes that the latter achieves a considerably lower response rate when administered to a larger patient group. We believe our results reflect the true activity of FCT and similar regimens when administered routinely to unselected patients. Considering the number of potentially serious side effects, we cannot recommend the moderately active FCT regimen as a palliative treatment option for melanoma patients.
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PMID:Clinical experience of fotemustine, cisplatin and high dose tamoxifen in patients with metastatic malignant melanoma. 991 19

We report a case of small intestinal metastasis from renal cell carcinoma (RCC) in a 57-year-old female. The patient had undergone partial nephrectomy for a right RCC (pT1aN0M0) in June 1997. She later developed multiple metastases, in the lungs, brain, and bone, and was admitted with nausea, vomiting, and appetite loss in April 2003. She presented with melaena a few weeks after her admission and a computed tomographic scan revealed a small bowel mass that was not definitively diagnosed. We removed the mass surgically, and the histological features confirmed the diagnosis as metastatic RCC. The patient recovered and could consume, but died of brain metastases 102 days after the surgery. Metastasis of RCC in the small bowel is a rare entity clinically. To our knowledge, this is only the 20th case of small intestinal metastasis from RCC reported in the Japanese and English literature.
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PMID:[Small intestinal metastases from renal cell carcinoma: a case report and literature review]. 1573 34

Although virtually any systemic malignancy is capable of metastasizing to the brain, ovarian carcinoma, one of the more common female genital malignancies, is one of the rarer forms of brain metastases. In general, the outcome for ovarian carcinoma with brain metastases is extremely poor as most of these patients have widespread lesions elsewhere. This report describes the first known case of multiple cerebral and leptomeningeal metastases as the initial manifestation of ovarian carcinoma in a 41-year old woman who presented with a one-week history of headache, vomiting and confusion. CT scan of the brain was unremarkable, but lumbar puncture revealed atypical cells in the CSF. MRI scan of the brain showed multiple small enhancing lesions. Craniotomy for excision of one of these lesions demonstrated metastatic adenocarcinoma. A large ovarian tumour identified on pelvic CT scan was resected and the patient subsequently received chemotherapy and radiotherapy. Unfortunately she continued to decline and died within six months. Unlike primary tumours such as malignant melanoma, ovarian carcinoma does not have a predilection for the central nervous system (CNS), but the rare instances with CNS involvement occur at an advanced stage of the disease. Once the CNS is involved, the outcome is abysmal, even with multimodality therapy. It is extremely unusual for ovarian carcinoma to present with multiple CNS involvement.
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PMID:Multiple cerebral and leptomeningeal metastases from ovarian carcinoma: unusual early presentation. 1611 53

Brain metastases from cervical carcinomas are extremely rare. We report a patient with squamous cell carcinoma of the cervix who developed an isolated left parietooccipital lobe metastasis within 4 months of treatment of the primary disease. The presenting symptoms of the metastatic disease were visual disturbance, headache, and vomiting. The patient was successfully treated by surgical excision of the metastasis and adjuvant whole brain radiation therapy, and she was disease-free at the 6-month follow-up after treatment of the recurrence.
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PMID:Brain metastasis from cervical carcinoma--a case report. 1636 31

The aim of this study was to evaluate the headache and other neurological symptoms and signs as guide predictors for the occurrence of brain metastases in cancer patients. We prospectively studied 54 cancer patients with newly appeared headache or with a change in the pattern of an existing headache during the recent months. All patients completed a questionnaire regarding headache's clinical characteristics and existence of accompanying symptoms. They also underwent a detailed neurological, ophthalmologic examination and brain neuroimaging investigation. Brain metastases were diagnosed in 29 patients. Univariate regression analysis showed an association between occurrence of brain metastases and nine clinical symptoms or signs. Multivariate regression analyses emerged only four of them as significant independent predictors. These were: bilateral frontal-temporal headache, more pronounced on the side of metastasis in cases of single metastases, with duration > or =8 weeks, pulsating quality and moderate to severe intensity (OR: 11.9; 95% CI. 2.52-56.1), emesis (OR: 10.2; 95% CI. 2.1-55.8), gait instability (OR: 7.4; 95% CI. 1.75-33.9) and extensor plantar response (OR: 12.1; 95% CI. 2.2-120.7). In conclusion, all cancer patients who manifest the above independent clinical predictors should be highly suspected for appearance of brain metastases and therefore should be thoroughly investigated.
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PMID:Headache characteristics and brain metastases prediction in cancer patients. 1644 82

The first discovery of a cerebellar metastasis of pancreatic carcinoma in a living patient is described. Two years earlier the patient had undergone a pancreaticoduodenectomy for an adenocarcinoma of the head of the pancreas with a lymph node metastasis. After complete surgical removal of the tumor, he underwent adjuvant chemoradiation. Two years later the patient presented with intractable vomiting, which was attributed to peritoneal carcinomatosis. Clinical evaluation revealed an intracranial tumor without signs of pancreatic recurrence. The tumor was surgically removed. One year later the patient developed multiple brain metastases and he is currently undergoing gemcitabine-based chemotherapy.
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PMID:Cerebellar metastasis from pancreatic adenocarcinoma. A case report. 1663 5


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