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)

Twenty-eight patients with refractory advanced malignancies were treated with a 24-hour infusion of 5-fluorouracil (5-FU), leucovorin (LV), and N-(phosphonacetyl)-L-aspartic acid (PALA) weekly. Twenty-seven patients were evaluable to assess toxicity and antitumor activity. The PALA was administered as an intravenous bolus over 15 minutes at a fixed dose (250 mg/m2) 24 hours before the start of the 5-FU and leucovorin infusions. Initially the dose of 5-FU was 750 mg/m2; this was increased incrementally to 2600 mg/m2. The LV was administered in a fixed dose of 500 mg/m2 concurrently with the 5-FU over a 24-hour period. This regimen was repeated weekly. Diarrhea, stomatitis, nausea, and vomiting were among the dose-limiting toxicities. Others were hand-foot syndrome, hair loss of the scalp and eyelashes, overall weakness, rhinitis, and chemical conjunctivitis. The maximum tolerated dose of 5-FU in this combination and schedule was 2600 mg/m2. Seven of 14 patients treated with 2600 mg/m2 were able to tolerate the chemotherapy on a weekly basis without interruption. The other seven patients required dose reductions, but most received 5-FU at a dose of 2100 mg/m2. Twenty-three of 27 patients were treated previously. Eight patients had a partial response; five of these were treated previously. A complete response was observed in one patient with pancreatic carcinoma, previously untreated. The overall response rate for patients treated with 2100 or 2600 mg/m2 of 5-FU was nine of 18 patients (50%). Three of four previously untreated patients with pancreatic cancer responded to this treatment (two responded partially, and one had a complete response). One of three heavily pretreated patients with non-small cell lung cancer had a partial response as did a patient with breast cancer. Four of ten patients with colorectal cancer responded to the treatment (four partial responses), of whom three had been treated previously.
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PMID:A phase I, II study of high-dose 5-fluorouracil and high-dose leucovorin with low-dose phosphonacetyl-L-aspartic acid in patients with advanced malignancies. 187 76

Thirty-six patients with recurrent carcinoma of the head and neck and no prior exposure to chemotherapy were treated with Ifosfamide. This drug was administered, concomitantly with Mesna, as a 24-hr infusion at a dose of 5-6.25 g/m2 every 3 weeks. Objective activity in 32 evaluable patients was 28% (9/32, 95% C.I. 17%-39%); 40% of patients had leukocyte values less than 2000 mm3 and 6% platelets less than 50,000 mm3. Nonhematologic toxicity consisted mainly of nausea/vomiting (66% greater than or equal to grade 2) and alopecia (80% greater than or equal to grade 2). The activity encountered warrants further studies with this drug in head and neck cancer.
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PMID:Phase II trial of ifosfamide in recurrent and metastatic head and neck cancer. 190 50

We conducted a phase II clinical trial of 5-fluorouracil (5 day continuous infusion), cis-diamminedichloroplatinum and etoposide in previously untreated patients with metastatic carcinoma of unknown primary origin. Of the thirty-six evaluable patients (21 adenocarcinoma, 14 undifferentiated carcinoma and 1 squamous cell carcinoma), eight patients responded to this treatment (4 CR, 4 PR). Responses were seen in both soft tissue and visceral disease. Toxicity was significant and included grade III/IV myelosuppression in over 90% of patients treated. Non-hematologic toxicity included nausea/vomiting and stomatitis. Although the remissions obtained in this study appear to be durable (median duration of complete remission greater than 24 months), the regimen does not appear to offer significant advantages over other less toxic and more easily administered cisplatin-based combinations.
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PMID:Continuous infusion 5-fluorouracil, etoposide and cis-diamminedichloroplatinum in patients with metastatic carcinoma of unknown primary origin. 191 61

Giving chemotherapy and radiotherapy simultaneously (concomitant therapy) is one approach to improving results in advanced head and neck cancer. To assess the feasibility of one such regimen, 25 patients with advanced squamous carcinoma of the head and neck were treated with a continuous intravenous infusion of 5-fluorouracil, 1 g/m2 per 24 h for Days 1-5 (105 h) and mitomycin-C 14 mg/m2 intravenously on Day 3 during the first week of radiotherapy. Twenty had Stage IV disease; four Stage III; and one Stage II. Ages ranged from 21 to 73 years (median 60 years). The tumours involved were as follows: oral cavity (6); nasopharynx (8); oropharynx (5); secondary node from unknown primary (3); hypopharynx (2); paranasal sinus (1). Radiotherapy was delivered as 10 Gy per week (total dose 60-70 Gy). Chemotherapy was well tolerated and all received the intended dose. Mild nausea occurred in five patients and three experienced transient vomiting. A generalized "early" mucositis affected 16 out of 25 (64%), caused interruption of radiotherapy in three patients, and is thought to be chemotherapy related. Twenty-two patients received the dose of radiotherapy intended, and two stopped prematurely at 53 and 56 Gy. Three episodes of neutropaenic infection occurred. Two recovered uneventfully, but one toxic death occurred in a patient with alcoholic cirrhosis. A complete response was seen in 21 (84%). For 17 patients with non-nasopharyngeal carcinoma the 2-year survival is 40%, 24% disease free. The concomitant use of 5-fluorouracil, mitomycin and radiotherapy is well tolerated in this group of patients.
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PMID:Concomitant chemo/radiotherapy for advanced carcinoma of the head and neck. 195 37

The safety, tolerance, and clinical effects of a home therapy regimen of recombinant human interleukin-2 (rIL-2) and interferon-alpha 2b (IFN-alpha 2b) self injected subcutaneously have been assessed in 35 patients with advanced cancer refractory to standard therapy. 52 treatment cycles were given, each consisting of a 2-day rIL-2 pulse of 9.0 million IU/m2 every 12 h, followed by 6 weeks of rIL-2 1.8 million IU/m2 twice daily for 5 days per week and of IFN-alpha 2b 5.0 million U/m2 thrice a week. The main adverse effects were fever, chills, nausea, anorexia, and hypotension and were limited to WHO grades of severity I and II in 29 of 35 patients. No treatment-related deaths occurred. The response rates among patients with renal-cell carcinoma were similar to those reported for high-dose intravenous regimens of interleukin-2 that are toxic and have to be given in hospital.
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PMID:Home therapy with recombinant interleukin-2 and interferon-alpha 2b in advanced human malignancies. 197 42

Tumor necrosis factor (TNF) is a cytokine with pleiotropic biological and antitumor effects in vitro and in mouse models. The immunological effects of the molecule as a single agent, however, have not been well studied clinically. We conducted a Phase I trial of TNF in 53 patients with advanced malignancies in order to determine the biological and clinical effects of TNF when administered as a 30-min i.v. infusion three times/week. Dose levels of TNF ranged from 5 to 275 micrograms/m2; doses of TNF were escalated between patient groups. The most common clinical toxicities of TNF consisted of rigors, anorexia, headache, and fatigue. Dose-limiting toxicity consisted of hypotension, fatigue, and nausea. Four patients treated at the maximally tolerated dose of 225 micrograms/m2 received dexamethasone to determine whether the toxicities of TNF could be ameliorated. No significant differences in hypotension or subjective symptomatology were observed in those patients receiving dexamethasone and those who did not or between injections in which dexamethasone was administered and when it was not. One patient with colorectal carcinoma treated with 50 micrograms/m2 had a partial response lasting about 9 months. Biological responses were evaluated in 8 patients treated at the maximally tolerated dose before therapy and 24 h afterward. TNF significantly (P less than 0.05 for all) enhanced serum beta 2-microglobulin, serum neopterin, and serum interleukin-2 receptor (Tac antigen) levels. Indoleamine 2,3-dioxygenase activity was also increased 24 h following the administration of TNF, although this increase was only of borderline statistical significance (P = 0.07). TNF did not enhance granulocyte bactericidal activity. The expression of cell surface proteins on monocytes, including HLA-DR, HLA-DQ, beta 2-microglobulin, and the Fc receptor, and serum interleukin-1 activity also were not significantly increased by the administration of TNF. Thus, in humans TNF caused biological response modulation with evidence of HLA Class I (beta 2-microglobulin) increase and T-cell (Tac antigen) and monocyte (neopterin) activation.
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PMID:Biological and clinical effects of intravenous tumor necrosis factor-alpha administered three times weekly. 199 56

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

Diaziquone (AZQ), a synthetic quinone with demonstrated activity against acute nonlymphocytic leukemia (ANLL), primary CNS tumors, and non-Hodgkin's lymphoma (NHL), is virtually devoid of nonhematopoietic toxicity at conventional doses. As a prelude to its inclusion into bone marrow transplant (BMT) preparative regimens, a phase I study of high-dose AZQ with autologous BMT (ABMT) was performed. Patients with refractory solid tumors and lymphomas were treated with a single 24-hour infusion of AZQ at 50 to 355 mg/m2 in dose escalations of 20%. Fifty-six patients received 69 courses. Those receiving greater than 60 mg/m2 had nadir granulocyte and platelet counts less than 500/microL and 20,000/microL, respectively. Nausea, vomiting, stomatitis, and diarrhea were mild, transient, and not dose-related. Transient minimal elevations of liver function tests were seen in five patients and were also not dose-related. The maximally tolerated dose (MTD) of high-dose AZQ was found to be 245 mg/m2, with nephrotoxicity being dose-limiting. Significant azotemia was seen in four of 12 patients treated at 295 and 355 mg/m2, including fatal anuric renal failure in three of these patients. Reversible proteinuria also occurred in 24 of 26 courses above 150 mg/m2, including nephrotic range proteinuria in eight courses, all at doses of 205 to 355 mg/m2. The proteinuria was also associated with multiple proximal tubular defects including generalized aminoaciduria and proximal renal tubular acidosis. There were six early deaths including two of early renal failure (295 and 355 mg/m2), two of sepsis (205 and 245 mg/m2), one of a pulmonary embolus (85 mg/m2), and one of progressive disease (60 mg/m2). Of 50 patients who were assessable for response, there were seven responses including two of 10 with primary CNS tumors, one of 12 with malignant melanoma, one of five with non-small-cell lung carcinoma, two of two with breast carcinoma, and one of one with ovarian carcinoma. Because of its activity in ANLL and NHL and its unique toxicity spectrum, high-dose AZQ may improve the efficacy of current BMT preparative regimens without significantly increasing their nonhematopoietic toxicity.
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PMID:A phase I trial of high-dose diaziquone and autologous bone marrow transplantation: an Illinois Cancer Council study. 207 48

A total of 32 evaluable patients with measurable advanced colorectal carcinoma were treated with continuous-infusion alpha-difluoromethylornithine (DFMO) at a median daily dose of 8 g/m2 (range, 6-14 g/m2). DFMO was infused over 24 h daily for 28 days, followed by a rest period of 7 days. Of the 32 patients, 14 had received no prior chemotherapy. A total of 65 courses was given, with the median being 2 (range, 1-9 courses). None of the patients achieved a partial or complete response; however, 3 patients achieved a minor response and 14 had stable disease. The frequent toxic effects of DFMO included thrombocytopenia (which was dose-limiting), malaise, nausea, vomiting, reversible hearing loss, and diarrhea. Our data suggest that continuous-infusion DFMO therapy is feasible and results in only mild gastrointestinal toxicity. Although DFMO proved to be ineffective as a single agent in this trial, it could probably best be used in combination with cytotoxic agents known to enhance its antitumor activity in a preclinical setting.
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PMID:Evaluation of continuous-infusion alpha-difluoromethylornithine therapy for colorectal carcinoma. 211 39

Doxifluridine (5'-dFUR) is a prodrug of 5 fluorouracil (5-FU) synthesized in an attempt to improve the therapeutic index compared with 5-FU. In this phase I study, cohorts of three patients were treated by a 5-day continuous infusion with the dose increased daily, total doses ranging from 3.75 g/m2 to 20 g/m2/120 h. Twenty-nine patients received 54 courses (median 2, range 1-4). The dose-limiting toxicities were mucositis (Miller grade 3 in three patients and grade 4 in another) and grade 4 neutropenia and thrombocytopenia in two patients. Other toxicities included nausea, vomiting, and diarrhea, rash, and fever. Neurological toxicity was mild and no cardiovascular toxicity was recorded. Plasma and urine levels of 5'-dFUR and 5-FU were quantitated by high-performance liquid chromatography. Steady-state plasma levels between 167 ng/ml and 6,519 ng/ml were recorded and at these levels there was no evidence of saturation of doxifluridine metabolism. One patient at the maximum tolerated dose of 20 g/m2/120 h had a complete response in a nasopharyngeal carcinoma.
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PMID:A phase I study of doxifluridine as a five-day stepped-dose continuous infusion. 214 51


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