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)

Docetaxel and ifosfamide have shown significant activity against a variety of solid tumours. This prompted a phase I trial on the combination of these drugs. This phase I study was performed to assess the feasibility of the combination, to determine the maximum tolerated dose (MTD) and the side effects, and to propose a safe schedule for further phase II studies. A total of 34 patients with a histologically confirmed solid tumour, who were not pretreated with taxanes or ifosfamide and who had received no more than one line of chemotherapy for advanced disease were entered into the study. Treatment consisted of docetaxel given as a 1-h infusion followed by ifosfamide as a 24-h infusion (schedule A), or ifosfamide followed by docetaxel (schedule B) every 3 weeks. Docetaxel doses ranged from 60 to 85 mg m(-2) and ifosfamide doses from 2.5 to 5.0 g m(-2). Granulocytopenia grade 3 and 4 were common (89%), short lasting and ifosfamide dose dependent. Febrile neutropenia and sepsis occurred in 17% and 2% of courses respectively. Non-haematological toxicities were mild to moderate and included alopecia, nausea, vomiting, mucositis, diarrhoea, sensory neuropathy, skin and nail toxicity and oedema. There did not appear to be any pharmacokinetic interaction between docetaxel and ifosfamide. One complete response (CR) (soft tissue sarcoma) and two partial responses (PRs) were documented. A dose of 75 mg m(-2) of docetaxel combined with 5.0 g m(-2) ifosfamide appeared to be manageable. Schedule A was advocated for further treatment.
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PMID:Phase I study on docetaxel and ifosfamide in patients with advanced solid tumours. 1064 11

Docetaxel is a new antimicrotubule agent that has been shown to be active against a variety of solid tumors. Ifosfamide is an alkylating drug that has demonstrated activity against non-small cell lung cancer, testicular cancer, breast cancer, and soft tissue sarcoma. This phase I study of the combination of these drugs was performed to assess the feasibility of using the two agents together, to determine the maximum tolerated dose and the side effects, and to propose a safe schedule for further phase II studies. Thirty-four patients with histologically confirmed solid tumors who had not been treated previously with taxanes or ifosfamide and who had received no more than one line of chemotherapy for advanced disease were entered into the study. Treatment consisted of docetaxel given as a 1-hour infusion followed by ifosfamide as a 24-hour infusion (schedule A), or ifosfamide followed by docetaxel (schedule B) every 3 weeks. Docetaxel doses ranged from 60 to 85 mg/m2 and ifosfamide doses from 2.5 to 5.0 g/m2. Grades 3 and 4 granulocytopenia were observed in 89% of courses and appeared to be of short duration and related to the ifosfamide dose. Febrile neutropenia and sepsis occurred in 17% and 2% of courses, respectively. Severe anemia and thrombocytopenia were uncommon. Nonhematologic toxicities were mild to moderate, and included alopecia, nausea, vomiting, mucositis, diarrhea, sensory neuropathy, skin and nail toxicity, hypersensitivity reactions, and edema. Schedule B appeared to induce more gastrointestinal toxicity than schedule A. One complete response in soft tissue sarcoma and two partial responses, one in cancer of unknown primary and the other in non-small cell lung cancer, were documented. The dose-limiting toxicity for schedule A was neutropenic fever at a dose of 85 mg/m2 docetaxel and 5 g/m2 ifosfamide. The dose-limiting toxicity for schedule B was neutropenic fever at a dose of 75 mg/m2 docetaxel and 4 g/m2 ifosfamide. A dose of 75 mg/m2 docetaxel combined with 5 g/m2 ifosfamide according to schedule A can be recommended for further studies.
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PMID:Docetaxel and ifosfamide in patients with advanced solid tumors: results of a phase I study. 953 8

The aim of this phase II trial was to examine the efficacy of a new nitrosourea, cystemustine, in soft tissue sarcoma. Between January 1990 and March 1991, 32 pretreated patients with advanced soft tissue sarcoma were enrolled. Cystemustine was given every 2 weeks at 60 mg/m2 via a 15-min i.v. infusion. All eligible patients were considered evaluable for response and toxicity (WHO criteria). Of the 32 enrolled patients, 4 were ineligible, leaving 28 evaluable patients. All but 1 had been pretreated: 6 with adjuvant chemotherapy, 18 patients with first-line palliative chemotherapy without nitrosourea, 3 with both treatments, and 18 had received radiotherapy. Median age was 54 years (range 20-73) and median performance status was 1 (0-2). One partial response (PR, duration 12 weeks), 2 stable disease and 25 progressions were observed, giving an overall response rate of 3.57% (confidence interval: 0.1-18.4%). Toxicity was mild, and was mainly neutropenia (no grade 3 or 4), thrombocytopenia (3.57% grade 3 and grade 4) and nausea-vomiting (no grade 3 or 4). It should be noted that the treatment for the patient who obtained a PR was third line with no previous response. Cystemustine with this schedule appears to have a low clinical activity and toxicity in advanced soft tissue sarcoma.
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PMID:Results of a phase II trial with second-line cystemustine at 60 mg/m2 in advanced soft tissue sarcoma: a trial of the EORTC Early Clinical Studies Group. 964 Feb 34

Exatecan mesylate (DX-8951f) is a new hexacyclic camptothecin analogue with favorable attributes compared to topotecan and CPT-11, including watersolubility, greater potency against topoisomerase I, lack of esterase-dependent activation, broad antitumor activity, and low cross-resistance against MDR-1 overexpressing tumors. In preclinical studies, the compound demonstrated a favorable toxicology profile with hematologic dose-limiting toxicity and moderate gastrointestinal toxicity, linear pharmacokinetics, P450 hepatic metabolism (CYP3A4 and CYP1A2), and predominately fecal excretion. The results of six U.S. and European phase I clinical trials as well as two Japanese studies are presented including total DX-8951 and lactone DX-8951 pharmacokinetics. The toxicity profile was similar for all schedules of administration. Hematologic toxicity was dose-dependent and reversible. Neutropenia was dose-limiting in minimally pretreated patients, whereas neutropenia and thrombocytopenia were dose-limiting in heavily pretreated patients. Non-hematologic toxicity included moderate gastrointestinal toxicity (nausea, vomiting > diarrhea), transient elevation of hepatic transaminases, asthenia, and alopecia. Two cases of acute pancreatitis not predicted by preclinical toxicology were also observed. Antineoplastic activity was detected in several solid tumor types: non-small cell lung cancer, extrapulmonary small cell cancer, colorectal cancer, hepatocellular cancer, and sarcoma. Antitumor activity was seen in CPT-11 and topotecan-resistant tumors. Pharmacokinetics were linear within the dose range tested. A pharmacokinetic/pharmacodynamic model predictive of DX-8951f-induced neutropenia in individual patients was developed. The daily x5, every 3-week schedule with the drug administered as a 30-minute intravenous infusion was selected for future phase II clinical trials based on its superior antitumor activity.
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PMID:DX-8951f: summary of phase I clinical trials. 1119 1

Primary meningeal sarcomas are rare but highly aggressive tumors predominantly affecting children. The clinical course, imaging characteristics and histopathological features of meningeal sarcomas in two pediatric patients are presented. Furthermore, we critically discuss the new WHO classification of these entities comparing them to older descriptions. In a 6-year-old girl, a cranial computed tomography (CT) scan was performed, after a mild head trauma, showing a parieto-occipital hemorrhage. One month later, a circumscribed mass adhering to the meninges and with central areas of hemorrhage was evident on magnetic resonance imaging (MRI) scans. Brain biopsy revealed a polymorphocellular sarcoma originating from the leptomeninges and infiltrating the brain. In an 8-year-old girl, who presented with headaches and vomiting, several MRI-examinations were inconspicuous for nearly one year until the latest MR-scan revealed a diffuse contrast enhancement of the leptomeninges of the whole brain and spinal canal. After open biopsy, primary leptomeningeal sarcomatosis was diagnosed. Although CT and MRI did not allow a specific diagnosis in both cases the exact visualization of the extent of the tumor and/or meningeal involvement was possible. Since there are no specific imaging criteria to differentiate meningeal sarcoma from other solid brain tumors or from other tumoral or inflammatory meningioses brain biopsy is indispensable. In order to avoid misinterpretations and delays of therapy, early open brain biopsy or surgical resection of the lesion is necessary in cases of unclear brain masses, especially of unclear meningeal processes. Due to the low number of cases published so far, the biological behavior and clinical management of this tumor entity still awaits further investigation.
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PMID:Primary meningeal sarcomas in two children. 1150 18

Primary sarcoma of the gallbladder is a rare disease. The tumor occurs more frequently in women. Usually gallstones are present. Symptoms resemble those of cholelithiasis or cholecystitis. The diagnosis is rarely made preoperatively. The patient was a 51-year-old woman with a 2-month history of right upper quadrant pain, nausea, vomiting, and a 10-pound weight loss. Ultrasound showed cholelithiasis and cholecystitis. Laparoscopic cholecystectomy was converted to open as a result of dense tissue in the middle to distal gallbladder. Exploration by a right subcostal incision revealed multiple implants on the surface of the liver and the peritoneum of the upper abdomen. The wall of the gallbladder was very thick and inflamed. Cholecystectomy with liver biopsy was performed. Pathology revealed poorly differentiated epithelioid leiomyosarcoma of the gallbladder with extension to the liver. The disease followed a very aggressive course and the patient died 3 weeks after the procedure. Recommended treatment is extensive surgical resection that can be followed by radiotherapy or chemotherapy. The tumor follows a very aggressive course, which often lasts a few weeks. Prognosis is poor with rare reported 5-year survivals.
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PMID:Leiomyosarcoma of the gallbladder: a case report. 1156 67

Gemcitabine (2',2'-difluorodeoxycytidine) is a nucleoside analog with antitumor activity against a variety of malignancies. The critical enzyme cytidine kinase is saturated at plasma concentrations achieved after a 30-min infusion at conventional doses. Prolonged infusion time may yield higher intracellular dFdCTP concentrations. A phase I study was designed to determine the maximum tolerated dose (MTD) of gemcitabine, given by infusion for 3 h, in heavily pretreated patients. Twenty-seven patients (13 head and neck cancer, seven sarcoma, three esophageal cancer, three non-small-cell lung cancer and one ovarian cancer) were enrolled. Twenty patients were defined as refractory at first- or second-line chemotherapy. Four different entry dose levels (300, 400, 450 and 500 mg/m(2)) were evaluated for gemcitabine administered on days 1, 8 and 15 of a 28-day cycle. The MTD was defined as 450 mg/m(2), with granulocytopenia, thrombocytopenia and asthenia being dose limiting. The maximum grade III/IV patient toxicities for hemoglobin, leukocytes, neutrophils and platelets for all doses were 7, 19, 19 and 11%, respectively. Non-hematological toxicities included asthenia, nausea/vomiting and diarrhea. Thus, gemcitabine administered at a fixed 3-h infusion was well tolerated up to 450 mg/m(2) in heavily pretreated patients. Myelosupression and asthenia were dose-limiting toxicities.
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PMID:Phase I trial of weekly gemcitabine at 3-h infusion in refractory, heavily pretreated advanced solid tumors. 1159 51

The purpose of this article is to describe the clinical and pathological features of metastatic angiosarcoma in the central nervous system. Only a few cases of cerebral metastasis from angiosarcoma of the heart have been recorded in the literature; particularly related to intracerebral hemorrhage. A case of secondary cerebral angiosarcoma of the heart in a 33 years old man is presented. The initial symptoms were headache, vomiting, lethargy and aphasia. There was a mass in the left temporal lobe with hemorrhage and edema on the computerized tomography (CT). After 24 hours the neurological status worsened and another CT scan showed rebleeding on the tumor area. He underwent an emergency craniotomy but died two days after. Considering the longer survival of sarcoma patients with new modalities of treatment, the incidence of brain metastasis may increase, demanding a better preventive and more aggressive approach. Besides, due to the hemorrhagic nature of such lesions, we suggest the immediate surgery to prevent a fast and lethal evolution because rebleeding.
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PMID:Hemorrhage in cerebral metastasis from angiosarcoma of the heart: case report. 1159 85

This report describes a rare case of multiple intracranial, extradural chloromas. A five year old African American male presented with headache, fever, and vomiting. The peripheral blood smear showed myeloblasts with Auer rods. The CTscan of the brain showed three intracranial, epidural lesions as well as soft tissue masses in the retroorbital region and sphenoid sinuses. CTscan of the chest showed two paraspinal epidural thoracic masses. Pathology of the epidural intracranial mass revealed a granulocytic sarcoma. Cytogenetic analysis showed simultaneous occurrence of t(8;21) and trisomy 8. Following induction therapy, he is now in complete remission.
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PMID:Multiple granulocytic sarcomas in acute myeloblastic leukemia with simultaneous occurrence of t(8:21) and trisomy 8. 1169 34

ET-743 is a novel antineoplastic DNA-binding agent derived from the marine tunicate Ecteinascidia turbinata. It has significant cytotoxic activity against soft tissue sarcomas (STS). It also has in vitro activity against melanoma, breast, ovarian, colon, renal, non-small cell lung and prostate carcinomas. The drug has unique mechanism of action which includes in vitro inhibition of transcription-dependent nucleotide excision repair pathways and inhibition of cell cycle progression leading to p53-independent apoptosis. It also selectively inhibits transcriptional activation of multidrug-resistance (MDR1) gene in human sarcoma cells in vivo. The efficacy of ET-743 has been investigated in patients with advanced STS in three multicentre phase II clinical trials. Patients receiving ET-743 as second- or third-line treatment had partial tumour response rates of 6 to 8%. Patients receiving ET-743 as first-line chemotherapy had a partial response rate of 18%. Forty-two to 50% of all patients in these trials achieved stable disease. All responses were durable up to 14 months. A pooled analysis of the three multicentre phase II trials showed the following: median overall survival time of 10.2 months, 1-year survival rate of 40% and 6-month progression-free rate of 27.2%. ET-743 is generally well tolerated. The most common adverse events in clinical trials were non-cumulative haematological and hepatic toxicities. Transient and reversible elevation of hepatic transaminases, nausea, vomiting and asthenia were common but seldom severe and never treatment-limiting. Mucositis, alopecia and cardiac or neurotoxicities were not observed.
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PMID:ET-743. 1201 79


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