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)

A clinical phase I-II evaluation of 2-amino-1,3,4-thiadiazole (A-TDA) administered daily, twice a week, or weekly was undertaken, in which 71 patients were treated with a range of doses from 2 mg/m2 to 200 mg/m2. Pharmacokinetic studies employing high-performance liquid chromatography (HPLC) demonstrated a terminal (beta) serum half-life of 2.19 h. Stomatitis, dermatitis, nausea, vomiting, and lethargy were observed. No significant leukopenia or thrombocytopenia, however, was noted. A-TDA administration led to hyperuricemia, which was adequately controlled with concurrent administration of allopurinol. Antitumor responses included one partial response in a patient with large cell carcinoma of the lung and three objective responses (2 non-small cell lung and 1 squamous cell carcinoma of the esophagus). Two patients with adenocarcinoma of the lung had a marked improvement of psoriasis during A-TDA therapy. Further phase II studies in patients with cancer and trials in patients with psoriasis are recommended.
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PMID:Clinical and clinical pharmacologic studies of 2-amino-1,3,4-thiadiazole (A-TDA:NSC 4728). 293 41

Twenty-four patients with advanced epidermoid carcinoma of the esophagus were treated with trimetrexate (TMTX), a lipid soluble non-classical antifol. Patients were given TMTX 8 mg/m2 intravenously day 1-5 every 28 days. In nine of these patients the dose was escalated to 12 mg/m2 day 1-5 every 28 days. Three patients had a partial response (95% confidence limit 3-32%) with a median response duration of 14 weeks. No hematologic toxicity was documented. Two patients developed moderate stomatitis and only 3 patients experienced any nausea or vomiting. The median survival of all patients is 12 weeks. It is concluded that a higher dose of TMTX should be studied in patients with esophageal cancer in order to assess the true therapeutic value of the agent at a dose closer to the median tolerated dose. A phase II ECOG study using TMTX 12 mg/m2 intravenously day 1-5 every 21 days is currently being conducted.
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PMID:Trimetrexate in advanced carcinoma of the esophagus. 297 10

A clinical trial of a new semi-synthetic podophyllotoxin, VP-16, was undertaken in patients with primary lung cancer; 56 of the 81 evaluable patients had small cell carcinoma, 9 adenocarcinoma, 8 epidermoid carcinoma, 7 large cell carcinoma, and 1 adenosquamous carcinoma. A dose of 200 mg/body/day orally for 5 consecutive days was administered every 3 to 4 weeks. Partial response (PR) was attained in 19 out of 81 (23%) and PR + MR was 35 out of 81 (43%). PR and minor response (MR) were seen as follows; small cell carcinoma, 17 PR (30%), 13 MR; epidermoid carcinoma, 2 PR (25%), 1 MR; adenocarcinoma, 1 MR; adenosquamous carcinoma, 1 MR. The dose-limiting factor was leukopenia, while thrombocytopenia was experienced in 2 cases. Clinical toxicities noted were anorexia, nausea, vomiting, stomatitis, diarrhea and alopecia, but these were well tolerated in all cases. The result indicated that VP-16 has considerable efficacy in small cell carcinoma and epidermoid carcinoma of the lung and hence its usefulness in combination chemotherapy was suggested.
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PMID:[A phase II study of oral VP-16 in primary lung cancer]. 299 76

In a phase II study of 67 patients with upper gastrointestinal carcinomas and measurable disease without previous chemotherapy, we have evaluated the combination of intensive course 5-fluorouracil (5-FU) (300 mg/m2/d for five days) doxorubicin (40 mg/m2 on day 1), and cisplatin (60 mg/m2 on day 1). Courses were repeated every 5 weeks. Among 26 patients with gastric carcinoma, a 50% regression rate was obtained with a median survival for all patients of 9 months. Among 29 patients with pancreatic carcinoma, the regression rate was 21% and the median survival was 4 months. Regressions were also observed in smaller numbers of patients with carcinomas of the gallbladder and ampulla of Vater, as well as in cholangiocellular carcinoma of the liver. Toxic reactions were usually clinically tolerable and consisted primarily of nausea, vomiting, stomatitis, diarrhea, leukopenia, and alopecia. Phase III studies are in progress to place the value of this experimental regimen into clinical perspective.
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PMID:A phase II study of combined 5-fluorouracil, doxorubicin, and cisplatin in the treatment of advanced upper gastrointestinal adenocarcinomas. 301 83

Twenty patients with disseminated cancer both untreated and previously treated received bialkylator chemotherapy, thiotepa, and cyclophosphamide and reinfusion of cryopreserved autologous bone marrow (ABMR). The cyclophosphamide dose was constant at 7.5 g/m2 over three days, while thiotepa was started at 1.8 mg/kg for three days in escalating dose by a modified Fibonacci schema to 7 mg/kg. The median time to recovery of more than 500 granulocytes and more than 50,000 platelets/microL was 18 and 27 days, respectively. Four patients died as a consequence of severe, overwhelming infections or progressive disease during their period of aplasia. Of the 18 evaluable patients, a complete response (CR) was achieved in three patients and a partial response (PR) in ten patients for an overall response rate of 72%. The median duration of response was 14 weeks. Other nonhematologic toxicities included nausea/vomiting, diarrhea, stomatitis, skin rash, and cardiomyopathy. The maximum tolerated dose (MTD) of thiotepa was 700 mg/m2 or 6 mg/kg for three doses. Although there are substantial toxicities associated with this regimen, high-dose thiotepa and cyclophosphamide produce high response rates in patients with disseminated cancer.
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PMID:A phase I-II study of bialkylator chemotherapy, high-dose thiotepa, and cyclophosphamide with autologous bone marrow reinfusion in patients with advanced cancer. 302 71

A phase II evaluation of vindesine (VDS) was performed in 16 patients with non-small cell lung cancer (ten patients with adenocarcinoma, six patients with squamous cell carcinoma, and one patient with large cell carcinoma). All except one of the patients had had prior chemotherapy. VDS at a dose of 3 mg/m2 was given intravenously every week for more than three weeks. Among 16 evaluable patients, two patients with pretreated adenocarcinoma of the lung showed partial response. The response rate for VDS was 12.5%. Toxic effects included leukopenia (94%), anemia (44%), thrombopenia (13%), alopecia (38%), peripheral neurotoxicity (38%), liver injury (19%), constipation (13%), anorexia (13%), nausea (13%), stomatitis (6%) and fever (6%).
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PMID:[A phase II study of vindesine for pretreated non-small cell lung cancer]. 303 21

Two trials of CF-FUra in patients with metastatic colorectal cancer were performed, both using a 3 day loading dose and then weekly maintenance doses to minimize toxicity. The first trial used CF by IV infusion with constant dose of FUra 400 mg/m2, and the second trial used oral CF with escalating doses of FUra. In the first trial, 45 eligible patients (20 with and 25 without prior therapy) were treated. Toxicity usually consisted of diarrhea or weakness and was controlled by delaying or decreasing 5FU dose. Subjective responses occurred in 75% of patients but did not correlate with antineoplastic effect. Objective responses were seen in 36% and stabilization of disease in 31% of patients, and correlated with prolonged survival. Median survival was 8 months for patients with prior treatment and 10 for those without, and 12 month survival was 32% and 40%, respectively. There was no correlation between the development of toxicity and response or survival. The second trial was recently conducted in cooperation with Duke University to determine toxicity and efficacy of oral CP with IV FUra prior to a randomized trial of this combination versus placebo with IV FUra. Eighteen patients were treated and serum levels of folates were obtained on 10. First toxicity occurred at FUra doses ranging from 375 to 850 mg/m2, and consisted of diarrhea in 9, lethargy in 7, nausea/vomiting in 4, dermatitis in 4, conjunctivitis in 2, hypersalivation in 2, stomatitis in 1, and profound granulocytopenia in 1. Response rate was 35% and stabilization was 35% with median survival of 14 months and 12 month survival of 56%.
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PMID:Clinical experience with CF-FUra. 307 55

The toxicities of oral Ftorafur (1 g/m2/day 1-21) and intravenous 5-fluorouracil (5-FU) (500 mg/m2/day 1-5) were compared in a prospective randomized study in patients with colorectal cancer. The treatment courses were repeated every 6th week. Leucopenia was more common after 5-FU. Leucocyte nadir in connection with first treatment cycle was on average seen on day 15 in patients receiving 5-FU and on day 28 in patients receiving Ftorafur. Significantly more patients on 5-FU developed stomatitis. There was no difference in the number of patients with diarrhea or nausea/vomiting. Median survival and response rates were not significantly different after the two treatment schedules.
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PMID:Oral ftorafur versus intravenous 5-fluorouracil. A comparative study in patients with colorectal cancer. 312 9

Twenty-three patients with metastatic adenocarcinomas were treated with long-term, continuous, ambulatory iv infusion of 5-FU. Length of infusion ranged from 54 to 324 days. The usual daily dose was 300 mg/m2. Toxicity was primarily stomatitis. Hand/foot syndrome occurred in 11 patients. Nausea, vomiting, myelosuppression, and alopecia were not observed. Thirteen patients had stomatitis. Eighteen patients had evaluable lesions; eight achieved partial response, five had stable disease, and five had progressive disease. Further studies are necessary to confirm the level of tumor response and survival period of patients treated with this method.
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PMID:Long-term, ambulatory, continuous IV infusion of 5-FU for the treatment of advanced adenocarcinomas. 315 49

Fifteen children with acute leukemia in relapse, refractory to conventional therapy, were treated with idarubicin administered orally for 3 consecutive days in dosages ranging from 30 to 50 mg/m2 per day at 19- to 21-day intervals. Gastrointestinal complications, including nausea, vomiting, abdominal pain, diarrhea and stomatitis, were the major forms of dose-limiting toxicity, affecting the majority of patients at all levels of idarubicin dosage. Two patients who had received total-body irradiation for bone marrow transplantation developed life-threatening gastrointestinal toxicity suggestive of a radiation "recall" phenomenon. Echocardiographic evidence of depressed cardiac function, without clinical symptoms or signs, was noted in six of 11 patients, although the changes were judged to be significant in only one child. The maximal tolerated oral dose of idarubicin was 40 mg/m2 per day. The medium terminal plasma half-life of idarubicin was 9.2 h (range, 6.4-25.5 h). Both idarubicin and its metabolite, idarubicinol, accumulated during the 3 days of therapy. Among the five patients with acute nonlymphoblastic leukemia whose cells were tested for drug sensitivity in vitro, the idarubicin concentration resulting in 50% inhibition (IC50) of cluster and colony formation ranged from 1.6 x 10(-10) M to 5 x 10(-7) M. There was no obvious relationship between the IC50 for idarubicin and that for epirubicin or daunorubicin. Oral idarubicin produced definite antileukemic effects, clearing blast cells from the circulation in 13 of the 14 evaluable patients. Future studies should define an optimal dose schedule to circumvent the limiting gastrointestinal complications associated with this agent.
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PMID:Phase I clinical trial of orally administered 4-demethoxydaunorubicin (idarubicin) with pharmacokinetic and in vitro drug sensitivity testing in children with refractory leukemia. 316 8


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