Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In Columbus, OH, 46 patients with measurable metastatic colorectal cancer were treated with leucovorin (LV) 80 mg/m2/20 h intravenous (IV) infusion followed by 5-fluorouracil (5-FU) 400 mg/m2 IV bolus daily for three days and then once weekly. Many patients had liver (62%) and/or multisite metastases (53%), carcinoembryonic antigen (CEA) greater than 10 (76%), documented tumor progression before entry (51%), and tumor-related symptoms (36%), but also good performance status (84%). Prior therapy consisted of radiotherapy (RT) in 18%, chemotherapy in 22%, both in 4%, and none in 56%. There were 36% objective responses and 31% stabilization, which we believe is a significant change in the natural history of these patients. Median survival was 8 months. Improved survival was seen in patients with single- rather than multiple-site involvement. Decreasing CEA levels were seen in 59% (always in responders or patients with stable disease), and correlated with longer survival time (11.0 v 5.5 months, P = 0.01). Palliation of tumor related symptoms occurred in 75%, with or without antitumor effect. One patient with prior RT died of neutropenic sepsis after only the three-day load, so we now recommend only weekly therapy in previously radiated patients. Otherwise, toxicity was mild, manifest as weakness in 62%, nausea in 53%, or diarrhea in 47%, which was the most common dose-limiting side effect. The occurrence or absence of toxicity did not predict outcome. Because of equivalent efficacy, mild toxicity, and less expense, this regimen should be considered for patients who desire therapy.
 ...
PMID:Leucovorin plus 5-fluorouracil: an effective treatment for metastatic colon cancer. 349 15

Sodium cyanate, a drug that selectively suppresses amino acid incorporation for protein synthesis in tumor tissue, was given to patients with advanced colorectal carcinoma who had failed to conventional therapy, with the purpose of assessing a maximum tolerable oral dose. At 35 mg/kg p.o. daily, the drug had to be stopped in approximately half (4) of the patients because of gastrointestinal toxicity (nausea, vomiting) and neurologic toxicity (hallucinations, disorientation). However, in 5 other patients, at the same dose, the drug was well tolerated for up to 147 days and for a total cumulative dose of 308 g. In this group of patients, sodium cyanate was stopped because of evidence of tumor progression. No hematologic toxicity was observed. We observed no therapeutic effects. We therefore recommend a starting dose of 30 mg/kg p.o. if a phase-II study is considered.
 ...
PMID:Phase-I clinical trial of sodium cyanate in patients with advanced colorectal carcinoma. 401 Nov 10

Twenty-three patients with non-small cell lung cancer were treated with a combination of cis-dichlorodiammineplatinum (II) 100 mg/m2 IV on day 1 and VP 16-213 80 mg/m2 IV on days 1-3. Eighteen patients are evaluable for response. Seven partial remissions with a median duration of 3 months (range, 1-13+) have been observed. Three patients exhibit stable disease, and eight patients show tumor progression. Overall survival was 5+ months (range, 1-13+); 7.5 months (range, 3-13+) for responders and 3+ months (range, 1-9+) for non-responders. Hematologic toxicity was acceptable, but poor subjective tolerance (nausea, vomiting, loss of appetite) was the main factor limiting treatment duration.
 ...
PMID:Cis-dichlorodiammineplatinum (II) and VP 16-213 combination chemotherapy for non-small cell lung cancer. 626 80

Sixty-two patients with previously untreated limited stage small cell lung cancer were treated in a prospectively randomized trial comparing thoracic irradiation plus combination chemotherapy with VP-16-213, vincristine (Oncovin), cyclophosphamide, and Adriamycin (VOCA) or those same four drugs plus low-dose (40 mg/m2) cisplatin (VOCAP). The addition of the cisplatin in eight courses of planned chemotherapy did not significantly improve either time to tumor progression of survival or alter sites of disease progression. It did, however, worsen the degree and frequency of nausea, vomiting, and myelosuppression. We did not identify any benefit from the usage of low-dose cisplatin as employed in this study.
 ...
PMID:An evaluation of low-dose cisplatin as part of combined modality therapy of limited small cell lung cancer. 626 70

Eleven women with advanced ovarian cancer were treated with a sequential and combined hormonal regimen designed to induce and bind tumor progesterone receptors. Two partial responses were seen, and two patients with a recent history of rapid tumor progression achieved disease stabilization. One patient experienced a transient ischemic cerebrovascular episode while on therapy, and a second patient discontinued therapy because of nausea. The regimen was able to induce progesterone receptors in vivo. One patient had no progesterone receptor in a pretreatment tumor biopsy, but did have a high titer of receptors after her first cycle of treatment.
 ...
PMID:Estrogen and progestogen therapy in advanced ovarian cancer: preliminary report. 665 79

Forty-one patients with advanced squamous cell lung cancer and no prior chemotherapy were entered in a prospectively randomized trial comparing dianhydrogalactitol plus Adriamycin (DA) versus DA plus cis-dichlorodiammineplatinum(II) (DAP). The DAP regimen was superior to the DA regimen in regression rate (53% versus 27%), median regression duration (255 versus 122 days), median time to tumor progression (approximately 175 versus 58 days), and median survival time (185 versus 126 days). Patients who were greater than 60 years old responded particularly well to the DAP regimen and accounted for most of the survival advantage. Nausea, vomiting, and myelosuppression were more frequent and severe with the DAP regimen. This study seems to indicate a role of cis-dichlorodiammineplatinum(II) in patients with advanced squamous cell lung cancer. The particular advantage noted for older patients needs further evaluation.
 ...
PMID:A role of cis-dichlorodiammineplatinum(II) in squamous cell lung cancer. 699 Nov 7

Androgen deprivation displays the mean therapy of advanced stage prostatic cancer. The development of hormone-resistant disease leads to a fatal tumor progression. High-dose fosfestrol (diethylstilbestrol disphosphate) has been suggested to circumvent hormone resistance and to induce a direct cytotoxic effect. Twenty-one patients with hormone-refractory prostate cancer were enrolled in a phase I trial of continuous infusion of high, daily escalating dose of fosfestrol. Fosfestrol was given in a 3.5 hr infusion in 0.9% normal saline at a starting dose of 1.5 g/d. The dose was increased daily in the same patient according to the following schedule: 1.5, 1.8, 2.4, 3.0, 3.6, 3.9, 4.5, 5.1 and 5.7 g/d. The duration of the infusion was prolonged to 7 or 10.5 hr, if a major side effect occurred. There was neither hematological nor cardiovascular toxicity. The main dose-limiting toxicities were nausea/vomiting in 17 patients, edema in 2 patients, and more than 5% weight gain in 3 patients. The planned maximal dose was reached in 10 patients during a 3.5 hr infusion, and in 3 additional patients, after infusion prolongation. Seven patients experienced a subjective improvement: Prostatic acid phosphatase and prostatic specific antigen decreased in 4 out of 11 and in 7 out of 12 patients, respectively. The suggested dose to phase II trial is 4 g/d in 3.5 hr infusion for a duration of up to 10 days.
 ...
PMID:Phase I trial of high-dose fosfestrol in hormone-refractory adenocarcinoma of the prostate. 750 21

Previous work has demonstrated the importance of the Protein Kinase C (PKC) signal transduction system in regulating the growth rate of malignant gliomas in vitro. Tamoxifen inhibits PKC in a minority of malignant gliomas within the micromolar concentration range in vitro, a property distinct from its estrogen receptor blockade effect. Tamoxifen was administered orally in very high dosages to 11 patients (9 males:2 females, age range 26-73, mean 45 years) with malignant gliomas (anaplastic astrocytoma or glioblastoma multiforme) who had failed treatment with external beam radiation therapy (and additional chemotherapy in 2). The dosage administered was estimated to be that necessary to achieve tissue concentrations within the low micromolar range, shown necessary to inhibit PKC in these tumors in vitro, and is approximately 5 times that used for standard antiestrogen therapy. Tumor reduction on radiographic images (MRI and PET [18FdG uptake]) with clinical improvement occurred in 3 patients; halting of tumor progression clinically and radiographically occurred in an additional patient. Of the remaining seven patients, three patients had marked and rapid progression of their disease despite treatment (dead after 3, 4, and 6 months respectively). Complications of treatment included a deep venous thrombosis requiring anticoagulation in one patient, nausea in one patient, and "hot-flashes" in a third patient. Tumor biopsy and measurement of tamoxifen and its active metabolite within the tumor of one patient (non-responder) showed levels within the middle of the in vitro therapeutic range. Follow-up of alive patients ranges from 4-18 months (mean 10 months). These encouraging preliminary results in a minority of these patients suggests some potential for this type of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Clinical and radiographic response in a minority of patients with recurrent malignant gliomas treated with high-dose tamoxifen. 838 28

Carboxyamido-triazole (CAI) is a synthetic inhibitor of non-excitable calcium channels that reversibly inhibits angiogenesis, tumor cell proliferation, and metastatic potential. Inhibition of calcium influx and calcium-dependent events is a potential common mechanism underlying these effects of CAI. The cytostatic and antiangiogenic properties of CAI led to its development for clinical investigation. In a Phase I clinical trial open to patients with refractory solid tumors, 49 patients received p.o. administered CAI daily or every other day. Two oral formulations, PEG-400 CAI solution and a gelatin capsule containing CAI in PEG-400, were tested. All administered dosages of CAI yielded plasma concentration at or above the range demonstrated to be effective in inhibiting signaling and cancer progression in vitro and in preclinical models (1 microgram/ml, 2.3 microM). Toxicity of p.o. administered CAI most commonly consisted of dose-related grade 1-2 nausea, vomiting, and occasional anorexia. CAI administration at bedtime ameliorated gastrointestinal complaints in many patients; others required addition of simple antiemetic regimens, usually consisting of metoclopropamide or prochlorperazine. Gastrointestinal complaints were the cause for compliance-limiting toxicity at 175 mg/m2/day of the liquid formulation and 125 mg/m2/day of the gelatin capsule formation. Reversible and rare sensory axonal neuropathy (grade 3, 1 patient) and neutropenia (grade 4, 1 patient) were dose-limiting toxicities observed at the 330 mg/m2 every-other-day liquid CAI dose level. No evidence of cumulative end organ damage or central nervous system injury was observed. Disease stabilization and improvement in performance status was observed. Disease stabilization and improvement in performance status was observed in 49% of evaluable patients who had disease progression before CAI. Disease stabilization and associated improvement in performance status was seen in patients with renal cell carcinoma (7 months), pancreaticobiliary carcinomas (3, 5, and 5 months), melanoma (7 months), ovarian cancer (7 months), and non-small cell lung cancer (3 months). The recommended Phase II doses from this trial are 150 mg/m2/day in the liquid formation and 100 mg/m2/day in the gelatin capsule formation.
 ...
PMID:Clinical investigation of a cytostatic calcium influx inhibitor in patients with refractory cancers. 856 73

This trial tested the assumed efficacy and safety of external beam-radiotherapy combined with daily administration of low dose cisplatin (CDDP) (ERCLC therapy) for patients with glioblastoma multiforme (GBM). Thirty adult patients with supratentorial GBM received daily postoperative treatment with low dose intravenous CDDP (4-6 mg/m2) administered 30 minutes before external irradiation. In 10 patients, intraoperative radiotherapy (IORT) following surgery was given prior to ERCLC therapy. Tumor response on MRI, interval to tumor progression, survival, and toxicities were analyzed. None of the patients showed a tumor response to ERCIC therapy. Overall, the median time to tumor progression was 6 months with a 1-year tumor progression-free rate of 26.7% and a 2-year rate of 0%. The median survival time was 15 months with a 1-year survival rate of 69.9% and a 2-year rate of 31.5%. The survival rate of patients with IORT was better than that of those without IORT, however, there was no significant difference. Anorexia associated with nausea occurred in 70% and general fatigue in 10.0%. Leukopenia and thrombocytopenia occurred in 26.7% and 33.3%, respectively. However, none of the patients had to be withdrawn from therapy due to these toxicities. Other toxicities were not observed. This clinical study showed that daily administration of low dose CDDP did not enhance tumor response to irradiation for GBM on MRI. Regarding toxicity, however, ERCLC therapy was well tolerated. Although this trial did not provide sufficient data to determine whether ERCLC therapy was effective for GBM due to the small number of patients, additional clinical trials of this therapy may be warranted because that the survival rate in this study was equal to the better results recently reported for newly diagnosed GBM.
 ...
PMID:Clinical trial of external beam-radiotherapy combined with daily administration of low-dose cisplatin for supratentorial glioblastoma multiforme--a pilot study. 926 43


<< Previous 1 2 3 4 5 6 7 Next >>