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)

To evaluate the efficacy and toxicity of high-dose epirubicin (EPI) plus cyclophosphamide (CPA) therapy, a phase II study of EPI, 130 mg/m2, plus CPA, 1000 mg/m2, with G-CSF every 3 weeks was carried out for 51 advanced or recurrent breast cancer patients by the Japan Clinical Oncology Group (JCOG). Fifty out of the 51 patients who were eligible for our criteria were treated with this regimen as first-line chemotherapy for visceral metastases or hormone-independent tumors. In this trial, 203 cycles were administered with an average of four cycles per patients. In 50 patients who were evaluable for response, there were 7 complete (CR) and 25 partial responses (PR) with an overall response rate of 64% (95% confidence interval, 50.1-75.9%). Symptomatic and hematological acute toxicity more than grade 3 occurred frequently; however, no treatment-related death occurred. The incidence of toxicities (> or = grade 3) was as follows: leukopenia 98%, thrombocytopenia 42%, nausea/vomiting 56% and hair loss 12%. In each cycle, daily administration of 2 micrograms/kg G-CSF (granulocyte-colony stimulating factor) was given on days 2-15 subcutaneously. The incidence of cardiotoxicity was low. Arrhythmia (< or = grade 2) was observed in 8% and a slight decrease of ejection fraction index (< or = grade 2) was observed in 2% in this trial. The median follow-up period for patients was 37.2 (24.6-51.5) months and the median survival period was 17.4 months. These data indicate that high-dose EPI + CPA combination chemotherapy was effective and well tolerated for breast cancer patients with visceral metastases or hormone-independent tumors. A randomized trial of high-dose EPI vs conventional chemotherapy is required to ascertain the usefulness of this regimen.
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PMID:A phase II study of high-dose epirubicin (EPI) plus cyclophosphamide (CPA) with G-CSF for breast cancer patients with visceral metastases or hormone-independent tumors: a trial of the Japan Clinical Oncology Group. 939 Feb 10

The purpose of this study was to determine the maximally tolerated dose of doxorubicin administered during two cycles of intensive chemotherapy with cyclophosphamide and doxorubicin without stem cell support in patients with advanced cancer and to assess the cumulative cardiac toxicity of the regimen by noninvasive radionuclide imaging and by pre-and postchemotherapy endomyocardial biopsies. Thirty-eight patients (thirty-six with high risk or metastatic breast cancer) were treated in a dose-escalation trial using a fixed dose of i.v. cyclophosphamide (4.2 g/m2) administered over 2 h on day 5 and escalating doses of doxorubicin (50-175 mg/m2) given as a 96-h continuous i.v. infusion on days 1-4, using Filgrastim (granulocyte colony-stimulating factor) for hematological support beginning on day 6. All patients underwent pretreatment, and 28 patients underwent postchemotherapy endomyocardial biopsies. Twenty-nine of 38 patients received two cycles of treatment (median number of days between cycles, 44; range, 34-62). Twenty-one patients had received doxorubicin previously at cumulative dose levels </=150 mg/m2; all patients had pretreatment endomyocardial biopsy scores less than 1. One patient treated at the highest dose level of doxorubicin (175 mg/m2) developed symptoms of mild congestive heart failure following two cycles of chemotherapy. Pre- and posttreatment radionuclide ejection fractions were 65 and 45%, respectively; this patient had a posttreatment endomyocardial biopsy score of 1 (damage to <5% of myocytes). One additional patient at this dose level had an asymptomatic biopsy score of 1, with a decrease in ejection fraction from 62 to 43%; this recovered to 58% 5 months after completion of chemotherapy. Six additional patients treated at lower dose levels had abnormal posttreatment endomyocardial biopsies without abnormal posttreatment ejection fractions. Nine patients received only one cycle of chemotherapy: five patients due to decreased cardiac ejection fraction following cycle 1 (two of these patients had normal endomyocardial biopsies, and two patients had biopsy scores of 1); one patient secondary to tumor progression following cycle one; one patient due to persistently detectable Clostridium difficile toxin in the stool; one patient refused cycle two; and one patient died following cycle one of complications related to sepsis. A single patient experienced a grand mal seizure associated with orthostatic hypotension, which was considered the dose-limiting toxicity. The median duration (over two cycles) of granulocytopenia (absolute granulocyte count <500/microliter) at the maximally tolerated dose level of 150 mg/m2 was 8.5 days (range, 5-13 days), and the median duration of thrombocytopenia (platelets <20,000/microliter) was 2.5 days (range, 0-9 days). The median duration of hospitalization including chemotherapy administration was 23 days (range, 19-36 days). Other toxicities included stomatitis, fever, diarrhea, and emesis. One patient developed acute leukemia 54 months posttreatment. We conclude that two courses of high-dose cyclophosphamide and doxorubicin using granulocyte colony-stimulating factor are feasible and safe with tolerable myocardial toxicity as evidenced by serial endomyocardial biopsies. The dose-limiting toxicity encountered was a grand mal seizure. The recommended Phase II dose is doxorubicin 150 mg/m2 administered as a 96-h infusion on days 1-4, with cyclophosphamide 4. 2 g/m2 on day 5 and G-CSF 5 microgram/kg/day started on day 6 and administered until the total WBC is above 10,000/microliter for three consecutive days.
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PMID:High-dose infusional doxorubicin and cyclophosphamide: a feasibility study of tandem high-dose chemotherapy cycles without stem cell support. 981 32

A 78-year-old female was admitted with complaints of malaise and fatigue in the legs. The patient was diagnosed as severe aplastic anemia and treatment was started with metenolone and steroid pulse therapy. Administration of antibiotics and granulocyte-colony stimulating factor which led to a resolution of the high fever. About four months after admission, the patient developed vomiting and abdominal pain with a spiking fever. The next day after suddenly losing consciousness, she died. B. cereus was isolated from blood cultures. Autopsy specimens of the liver, cardiac muscle and lung showed changes due to B. cereus. This pathogen is widely distributed in nature. We should not overlook B. cereus as a contamination, but rather should consider it a potential pathogen in immunocompromised hosts, when it is isolated from blood cultures.
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PMID:[Bacillus cereus septicemia in a patient with severe aplastic anemia]. 991 22

Escalating doses of cyclophosphamide were given every 3 weeks as adjuvant treatment for women operated for breast cancer to determine the maximum tolerated dose of cyclophosphamide that can be given with constant doses of methotrexate (40 mg/m2) and 5-FU (600 mg/m2; CMF) as an outpatient treatment without the routine use of granulocyte colony-stimulating growth factor (G-CSF). The dose of cyclophosphamide was increased by 250 mg/m2 starting from the dose of 1,000 mg/m2. Mesna was given to prevent cystitis. The criteria for dose-limiting toxicity were grade IV granulocytopenia lasting for longer than 48 h, granulocytopenic infection or other grade IV toxicities. G-CSF and ofloxacin were used if grade IV granulocytopenia continued for longer than 48 h or if granulocytopenic infection occurred. At the dose level of 1,500 mg/m2 (500 mg/m2/week) 22 (92%) of the 24 patients had grade IV granulocytopenia during the 6 CMF cycles given, but only 3 (13%) had granulocytopenic fever. G-CSF was used in 28% of the cycles at this dose level. Other toxicities included complete alopecia (79%), nausea and vomiting. Sixteen (80%) of the premenopausal women became postmenopausal. At the dose level of 1,750 mg/m2 all 3 patients treated had to be hospitalized after the first cycle due to neutropenic infection (n = 2) or intractable vomiting even though prophylactic G-CSF was used. We conclude that intravenous CMF with a cyclophosphamide dose of 1,500 mg/m2 given at 3-week intervals with the selective use of prophylactic G-CSF is feasible as adjuvant treatment for patients with breast cancer.
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PMID:Intensified adjuvant cyclophosphamide, methotrexate and 5-fluorouracil therapy: a dose-finding study for ambulatory patients with breast cancer. 994 94

Isovaleric acidemia, an autosomal recessive disorder, is due to isovaleryl-coenzyme A dehydrogenase deficiency and is one of the branched-chain aminoacidopathies. Isovaleric acidemia may present in the neonatal period with an acute episode of severe metabolic acidosis, ketosis, and vomiting and may lead to coma and death in the first 2 months of life. This report concerns an infant who presented at 10 days of age because of lethargy, poor feeding, hypothermia, cholestasis, and thrombocytopenia, leukopenia, and profound pancytopenia. Death occurred at 19 days of age. Autopsy showed mild fatty change in the liver and extramedullary hematopoiesis, generalized Escherichia coli sepsis, and myelodysplasia of the bone marrow with arrest of the myeloid series at the promyelocytic stage. The appearance resembled promyelocytic leukemia, but the diagnostic 15:17 translocation was not present. The maturation arrest in granulopoiesis in isovaleric acidemia appears to be most likely due to a direct metabolic effect on granulocyte precursor cells.
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PMID:Isovaleric acidemia with promyelocytic myeloproliferative syndrome. 1019 53

Clinical study has been conducted to evaluate the efficacy of chemotherapy with docetaxel and cisplatin in six patients with advanced non-small cell lung cancer. Treatment schedule consisted of docetaxel 60 mg/m2 and cisplatin 80 mg/m2 on day 1 and repeated every 4 weeks. Eligible patients had histologically proven locally advanced or metastatic non-small cell lung cancer, PS < or = 2, age < or = 74, normal hematological, hepatic and renal functions and informed consent in writing. Six patients have been included; all were males, median age 64 (range 47-74), histology; adenocarcinoma 4, squamous cell carcinoma 2, stage III B 4, stage IV 2. Among these 6 patients, 3 PR (50%) were observed. Neutropenia was the most common adverse event (83%). The lowest granulocyte counts were most frequently seen on day 9.4 (range: 6-14). Non hematologic adverse events included alopecia (6 cases), general fatigue (5 cases), anorexia (5 cases) and emesis (3 cases). These events were recovered rapidly with no therapy. The results suggest that combination chemotherapy of docetaxel and cisplatin will be effective and safe under careful observation.
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PMID:[Evaluation of chemotherapy with docetaxel and cisplatin in advanced non-small cell lung cancer]. 1039 19

9-Aminocamptothecin (9-AC) is a camptothecin derivative with broad antitumor activity in preclinical studies. Prior investigations suggested that prolonged maintenance of 9-AC lactone plasma concentrations above 10 nmol/l and frequent administration of the drug are important determinants of antitumor activity. Our phase II study, therefore, examined a 5-day continuous infusion of 9-AC weekly for 3 weeks in patients with advanced colorectal cancer. Eighteen patients previously untreated for metastatic disease received 480 microg/m2/day of 9-AC. No responses were observed in 17 evaluable patients. Severe toxicities included granulocytopenia, nausea, vomiting and diarrhea. The median absolute granulocyte count (AGC) nadir was 2,300/microl (range 0-9,000/microl) and occurred on day 10. Eight patients received an escalated dose of 600 microg/m2/day. The median AGC nadir at the escalated dose was 1,500/microl (range: 300-2,700/microl) and occurred on day 22. The median number of courses given was 2 (range: 1-8); and the median time to disease progression was 8 weeks (range: 1-40 weeks). 9-AC administered by this schedule lacked antitumor activity in patients with advanced colorectal carcinomas.
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PMID:Phase II trial of 9-aminocamptothecin (NSC 603071) administered as a 120-hr continuous infusion weekly for three weeks in metastatic colorectal carcinoma. 1042 69

We reported previously that the addition of recombinant Escherichia coli human granulocyte-macrophage colony stimulating factor (GM-CSF) to a 5-fluorouracil (5-FU) and leucovorin (LV) regimen seemed to ameliorate diarrhea and permit increased 5-FU dose intensity (J. L. Grem et al., J. Clin. Oncol., 12: 560-568, 1994). We then tested the effect of GM-CSF given with a more toxic regimen of 5-FU/LV/IFN-alpha (IFN alpha-2a). Thirty-one patients with a good performance status and no prior chemotherapy for systemic disease received IFN alpha(-2a (5 MU/m2 s.c., days 1-7), 5-FU (370 mg/m2 i.v., days 2-6), LV (500 mg/m2 i.v., days 2-6), and GM-CSF (Saccharomyces cerevisiae 250 microg/m2 s.c., days 7-18) every 3 weeks. Toxicities and 5-FU dose intensity were compared with that observed in our prior Phase II trial with 5-FU/LV/IFN alpha-2a (J. L. Grem et al., J. Clin. Oncol., 11: 1737-1745, 1993). In comparison with the prior Phase II study, the WBC and granulocyte nadirs in the present trial were significantly higher. When trends in toxicity grades for all cycles were compared, stratifying for 5-FU dose, the incidence and severity of mucositis, skin rash, WBC toxicity, and granulocyte toxicity were significantly lower in the present trial, whereas nausea/vomiting and fatigue were significantly worse. The delivered 5-FU dose intensity for all cycles of therapy appeared to be significantly higher in the present trial. Six of 28 evaluable patients had a partial response (21.4%), and 13 (46%) had stable disease for > or =12 weeks. Despite treatment-related toxicity, patient quality of life did not worsen during the study. No correlation was observed between thymidylate synthase content in primary tumor specimens and response, time to treatment failure, or survival. The addition of GM-CSF appeared to decrease the severity of leukopenia, granulocytopenia, mucositis, and skin rash when compared with our prior experience with this regimen of 5-FU/LV/IFN alpha-2a, at the cost of greater nausea/vomiting and fatigue. The potential impact of increased 5-FU dose intensity on clinical response, however, remains to be determined.
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PMID:A pilot study of interferon alpha-2a, fluorouracil, and leucovorin given with granulocyte-macrophage colony stimulating factor in advanced gastrointestinal adenocarcinoma. 1049 10

Malignant fibrous histiocytoma arising from the alimentary tract is extremely rare. We experienced a young patient with an inflammatory type of malignant fibrous histiocytoma in the jejunum which produced granulocyte-colony stimulating factor. A 16-year-old male was admitted to Umehara Hospital with abdominal pain, frequent vomiting of 2 days' duration, high fever and leukocytosis. Serum level of granulocyte-colony stimulating factor was 61.2 pg/mL. Plain abdominal X-ray, ultrasonography and computed tomography led to the diagnosis of intussusception with small intestinal tumor. On the 2nd hospital day, the patient underwent exploratory laparotomy. The jejunum showed intussusception with a hen's egg-sized tumor. After manual reduction, a 20-cm segment of the jejunum was removed. The patient was alive and doing well 29 months after the operation. Microscopic examination of the resected tumor disclosed an inflammatory type of malignant fibrous histiocytoma in the jejunum, and immunohistochemistry was positive for granulocyte-colony stimulating factor. This is the 5th case of malignant fibrous histiocytoma arising from the small intestine that has been described in the English literature.
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PMID:G-CSF producing malignant fibrous histiocytoma in the jejunum: a case report. 1114 20

A 55-year-old man was admitted to our hospital with fever and vomiting. Abdominal computed tomography (CT) revealed multiple low density masses in the liver. A diagnosis of primary adenosquamous carcinoma of the liver was confirmed by histological examination of a necropsy specimen. The present case showed leukocytosis and hypercalcemia with high levels of serum granulocyte-colony-stimulating factor (G-CSF) and parathyroid hormone related protein (PTHrP). Recent studies have shown that G-CSF and PTHrP are responsible for the paraneoplastic syndromes with leukocytosis and hypercalcemia. The tumor cells demonstrated positive cytoplasmic immunohistochemistry staining with anti-G-CSF and anti-PTHrP antibodies. This result suggested that the tumor produced G-CSF and PTHrP.
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PMID:Primary adenosquamous carcinoma of the liver which produces granulocyte-colony-stimulating factor and parathyroid hormone related protein: association with leukocytosis and hypercalcemia. 1150 5


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