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

In vitro studies have documented the synergistic activity of interferon (IFN) and fluorouracil (5-FU) in human cancer cell lines, and recent clinical trials have demonstrated the efficacy of this combination in metastatic colon cancer. The current study was undertaken to evaluate the combination of IFN alpha-2a plus 5-FU in previously untreated patients with metastatic renal cell carcinoma. From May 1990 through August 1990, 14 patients with metastatic renal cell carcinoma were treated with 5-FU 750 mg/m2/day continuous infusion IV days 1-5, followed by weekly IV infusions of 5-FU 750 mg/m2 beginning on day 12. Patients concurrently received IFN alpha-2a 9 x 10(6) IU subcutaneously 3 times per week beginning on day 1. The median age of patients treated was 57 (range 38-80) with a median Karnofsky performance status of 90 (range 60-100). Sites of metastases included lung only in 6 patients, liver only in 1 patient, 1 patient had bilateral disease at presentation, and the remaining patients had multiple sites of metastases. The median duration of therapy was 2 months. The predominant toxicities seen were stomatitis, nausea, flu-like symptoms and neurotoxicity. The only grade IV toxicity observed was severe vomiting in 1 patient, though 5 patients discontinued therapy within 2 months because of poor subjective response. With a minimum follow-up of 13 months no objective responses were seen. Thirteen of the 14 patients have had progressive disease and 11 have died. The median time to progression was 2 months (range 0.5-6 months) and the median survival was 5 months (range 2-14.5 + months).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A phase II trial of interferon alpha-2A plus fluorouracil in advanced renal cell carcinoma. A Hoosier Oncology Group study. 142 32

The chemistry, pharmacology, pharmacokinetics, assay methodologies, adverse effects, and dosage of levamisole are described, and the clinical studies of levamisole therapy in patients with colorectal carcinoma are reviewed. Levamisole is a synthetic, orally active agent that has antihelmintic and immunomodulatory properties. It is capable of inducing T-cell differentiation and restoring depressed effector functions of peripheral lymphocytes and phagocytes to normal. The drug is well absorbed from the gastrointestinal tract after oral administration and is extensively metabolized by the liver. Gas chromatography and high-performance liquid chromatography are the most common methods used to measure concentrations of levamisole in biologic fluids. Levamisole combined with fluorouracil has been associated with a one-third reduction in recurrence and risk of death in patients with surgically resected Dukes stage C colon cancer; this combination is now recommended as standard therapy in these patients. Uses in patients with rectal carcinoma, Dukes stage B colon cancer, metastatic colon cancer, other malignancies, or nonmalignant disorders remain investigational. Common adverse effects include nausea, abdominal pain, vomiting, diarrhea, metallic or altered taste, flulike symptoms, mood elevation, insomnia, hyperalertness, dizziness, and headache. The most serious adverse effect associated with levamisole is granulocytopenia. The FDA-approved dosage of levamisole is 50 mg orally every eight hours for three days every two weeks. Levamisole therapy is to be initiated no earlier than 7 and no later than 30 days after surgery and is to be continued for one year. Levamisole combined with fluorouracil has been associated with a one-third reduction in recurrence and risk of death in patients with resected stage C colon cancer. Further research is needed to more clearly define the mechanism of action, optimum dose and scheduling, and clinical efficacy of levamisole in treating other malignancies.
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PMID:Levamisole in the adjuvant treatment of colon cancer. 200 37

2B1 is a bispecific murine monoclonal antibody (BsMAb) with specificity for the c-erbB-2 and Fc gamma RIII extracellular domains. This BsMAb promotes the targeted lysis of malignant cells overexpressing the c-erbB-2 gene product of the HER2/neu proto-oncogene by human natural killer cells and mononuclear phagocytes expressing the Fc gamma RIII A isoform. In a Phase I clinical trial of 2B1, 15 patients with c-erbB-2-overexpressing tumors were treated with 1 h i.v. infusions of 2B1 on days 1, 4, 5, 6, 7, and 8 of a single course of treatment. Three patients were treated with daily doses of 1.0 mg/m2, while six patients each were treated with 2.5 mg/m2 and 5.0 mg/m2, respectively. The principal non-dose-limiting transient toxicities were fevers, rigors, nausea, vomiting, and leukopenia. Thrombocytopenia was dose limiting at the 5.0 mg/m2 dose level in two patients who had received extensive prior myelosuppressive chemotherapy. Murine antibody was detectable in serum following 2B1 administration, and its bispecific binding properties were retained. The pharmacokinetics of this murine antibody were variable and best described by nonlinear kinetics with an average t 1/2 of 20 h. Murine antibody bound extensively to all neutrophils and to a proportion of monocytes and lymphocytes. The initial 2B1 treatment induced more than 100-fold increases in circulating levels of tumor necrosis factor-alpha, interleukin 6, and interleukin 8 and lesser rises in granulocyte-monocyte colony-stimulating factor and IFN-gamma. Brisk human anti-mouse antibody responses were induced in 14 of 15 patients. Several minor clinical responses were observed, with reductions in the thickness of chest wall disease in one patient with disseminated breast cancer. Resolution of pleural effusions and ascites, respectively, were noted in two patients with metastatic colon cancer, and one of two liver metastases resolved in a patient with metastatic colon cancer. Treatment with 2B1 BsMAb has potent immunological consequences. The maximum tolerated dose and Phase II daily dose for patients with extensive prior myelosuppressive chemotherapy was 2.5 mg/m2. Continued dose escalation is required to identify the maximally tolerated dose for patients who have been less heavily pretreated.
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PMID:Phase I trial of 2B1, a bispecific monoclonal antibody targeting c-erbB-2 and Fc gamma RIII. 755 34

Fazarabine (Arabinofuranosyl-5-azacytosine) is a synthetic pyrimidine nucleoside which combines the arabinose sugar of cytosine arabinoside with the triazine base of 5-azacytidine. It has demonstrated activity against a variety of human solid tumor xenografts including colon, lung and breast cancers. Eighteen patients with refractory metastatic colon cancer were enrolled in a phase II trial of fazarabine. The drug was administered as a 72 hr continuous infusion every 3-4 weeks; the starting dose was 2 mg/m2/hr as established in a previous phase I study. The major toxicity was neutropenia, as predicted from the phase I study. The median time to nadir for cycle 1 was 20 days, with a median granulocyte count of 437/microliters (range 36-1600/microliters); recovery was within 2-4 days, with only one incidence of fever and neutropenia in 42 cycles. Especially noted for their absence were thrombocytopenia, nausea, vomiting and stomatitis. No objective clinical responses were seen; one patient had stabilization of rapidly growing liver metastases for a period of 7 months. In view of fazarabine's narrow range of toxicities, future dose intensification trials utilizing fazarabine in combination with hematopoietic growth factors are worthy of consideration.
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PMID:Phase II study of fazarabine (NSC 281272) in patients with metastatic colon cancer. 768 14

Preclinical and clinical models have demonstrated that cyclooxygenase-2 (COX-2) is overexpressed in primary and metastatic colorectal tumors. In preclinical models, there appears to be additive or synergistic effects when combining 5-Fluorouracil (5-FU) with nonsteroidal anti-inflammatory agents (NSAIDs) for the treatment of colorectal neoplasms. This data raised the question as to whether adding a COX-2 inhibitor to 5-FU-based regimens would increase the response rates with an acceptable toxicity profile in patients with metastatic colon cancer. In the current study, patients with metastatic colorectal cancer, who were either untreated or previously treated (more than 1 year ago) with adjuvant 5-FU and Leucovorin (LV) received 5-FU and LV (Mayo regimen) in addition to Rofecoxib. Tumor samples from all patients exhibited evidence of moderate COX-2 over-expression. 4 patients entered on the study developed upper gastrointestinal bleeding (grade III). Other toxicities included grade II stomatitis (3 patients), grade II thrombocytopenia (1 patient), grade II diarrhea (2 patients) and grade I nausea (1 patient). There were no partial or complete responses in the first 10 patients entered on the study so the study was terminated (probability of success < 0.3 with type 1 error of 0.05 and power of 0.8). Thus, Rofecoxib did not appear to increase antitumor activity and resulted in increased gastrointestinal toxicity when combined with 5-FU/LV. Future studies will need to consider the added gastrointestinal toxicity of Rofecoxib when combined with chemotherapy for the treatment of patients with colorectal cancer.
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PMID:Increased toxicity and lack of efficacy of Rofecoxib in combination with chemotherapy for treatment of metastatic colorectal cancer: A phase II study. 1506 99

The objective of this study was to define the maximally tolerated dose (MTD) and response rate of a combination of two topoisomerase I inhibitors, topotecan and irinotecan, in patients with metastatic colon cancer. Eleven patients, the majority with previously progressive disease on 5-fluorouracil-based regimens, were enrolled onto a phase I/II dose escalation trial utilizing continuous infusion topotecan for 2 weeks and weekly irinotecan x 3 with cycles repeated every 28 days. Dosages of topotecan utilized included 0.2 and 0.25mg/m2/day. Irinotecan was administered at a dose of 62 mg/m2 by i.v. bolus. Patients were followed for toxicity and response. The MTD of the combination of agents was found to be 0.25mg/m2/day for topotecan and 62 mg/m2 for irinotecan. The most common serious toxicities were diarrhea and nausea/vomiting. Only one patient experienced grade III neutropenia. There were no complete or partial responses. However, four patients had prolonged disease stabilization (SD) of up to 324 days and this group remained on protocol therapy for an average of 227 days (p=0.0005 versus patients not achieving SD). We concluded that the MTD for this combination of topoisomerase I inhibitors, given on this particular schedule, has been defined. This combination cannot be recommended as a first- or second-line therapy for patients with metastatic colon cancer based on the responses observed. However, approximately one-third of patients achieved prolonged disease stabilization. Topotecan with irinotecan may be useful as a palliative regimen for a subgroup of colon cancer patients.
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PMID:Combined topoisomerase I inhibition for the treatment of metastatic colon cancer. 1520 98

Hypercalcemia is rarely associated with colon cancer. It is related to overexpression of parathyroid hormone-related protein (PTH-rp) in malignant cells of the primary colon tumor and metastases. A 44 year old lady presented for evaluation of severe hypercalcemia (15.7 mg/dL) associated with abdominal pain, nausea and constipation. She was diagnosed with metastatic colon cancer involving the liver. Therapy for hypercalcemia consisted of intravenous bisphosphonate and saline hydration. Hypercalcemia remained resistant and refractory to treatment despite resection of the colon tumor. She died soon after admission to hospice. It is proposed that malignant cells of the primary colon tumor and distant metastases, in this patient, were the site of ectopic PTH-rp secretion resulting in hypercalcemia. This case illustrates the significance of recognizing hypercalcemia as a potential clue in detecting underlying colon cancer involving overproduction of PTH-rp. It also exemplifies the poor prognosis expected with this type of humoral hypercalcemia of malignancy and the difficulty encountered when trying to achieve normalization of calcium in this setting.
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PMID:Hypercalcemia as a Presenting Clinical Manifestation of Adenocarcinoma of the Colon. 2914 4

A 61-year-old man underwent CapeOX plus bevacizumab chemotherapyafter right hemicolectomyfor metastatic ascending colon cancer. On the 7th dayafter the first administration, he had sudden abdominal pain and nausea. Contrast-enhanced computed tomographyrevealed aortic thrombosis and a superior mesenteric artery(SMA)embolism that was considered to be associated with bevacizumab. Bevacizumab was discontinued and anticoagulation therapyusing heparin and urokinase was performed. Brain infarction of the left middle cerebral arteryoccurred on the 15th dayafter the first administration and thrombectomywas performed. Anticoagulation therapyusing heparin, bayaspirin, and edoxaban tosilate hydrate was performed. The aortic thrombosis and SMA embolism resolved with treatment, but the patient died following an increase in peritoneal dissemination. It should be noted that unexpectedlysevere aortic thrombosis occurred during the first administration of CapeOX plus bevacizumab for metastatic colon cancer.
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PMID:[A Case of Severe Aortic Thrombosis during the First Chemotherapy Regimen of CapeOX plus Bevacizumab for Metastatic Colon Cancer]. 3254 Nov 81