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 hr infusion of 5-fluorouracil (5-FU), Leucovorin (LV), and N-(phosphonacetyl)-L-aspartic acid (PALA) weekly. Twenty-seven patients were evaluable for the assessment of toxicity and anti-tumor activity. PALA was administered as intravenous bolus over 15 min at a fixed dose, 250 mg/m2 24 hr before the start of 5-FU and LV infusions. 5-FU was initially administered at 750 mg/m2 and was incrementally increased to 2600 mg/m2. LV was administered in a fixed dose of 500 mg/m2 concurrently with 5-FU over a 24-hr period. The course was repeated weekly. Diarrhea, stomatitis, nausea, and vomiting were among dose-limiting toxic effects. Other toxicities observed were hand-foot syndrome, hair loss of scalp/eyelashes, overall weakness, rhinitis, and chemical conjunctivitis. Maximum tolerated dose (MTD) of 5-FU in this combination and schedule was 2600 mg/m2. Seven of 14 patients treated at 2600 mg/m2 were able to tolerate the chemotherapy on a weekly basis without interruption. The other seven patients required dose de-escalation, a majority of whom contained 5-FU at a dose of 2100 mg/m2. Twenty-three of 27 patients had been previously treated. Eight patients achieved a partial response, all of whom were previously treated, except three patients. A complete response was observed in a patient with pancreatic carcinoma, previously untreated. Overall response rate for the patients who were treated at the 5-FU dose of 2100 mg/m2 or 2600 mg/m2 is 9 of 18 patients (50%).
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PMID:Phase I study of high dose 5-fluorouracil and high dose Leucovorin with low dose phosphonacetyl-L-aspartic acid in patients with advanced malignancies. 173 89

Forty-nine patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) were treated with 3 cycles of induction chemotherapy prior to definitive local treatment (surgery and/or radiation therapy). Chemotherapy consisted of carboplatin 300 mg/m2 on day 1, fluorouracil 1000 mg/m2 daily as a continuous infusion on days 1 to 5 and high-dose methotrexate 1.2 g/m2 with leucovorin rescue on day 14. After completing the induction chemotherapy, 9 patients (18%) achieved a complete remission (CR), 26 (54%) a partial remission (PR), 7 had stable disease and 7 a progression. The response rates increased to 53% CR and 18% PR following locoregional treatment. Survival at 12 months was 61% and its actuarial probability at 24 months 31%. Median time to progression was 14 months. Toxicity from chemotherapy was generally mild. Nausea was observed in 35%, vomiting in 26%, stomatitis in 57%, anemia in 22%, leukopenia in 36%, thrombocytopenia in 26% and diarrhea in 6% of the patients. In conclusion, the combination of carboplatin, 5-day continuous-infusion fluorouracil and mid-cycle high-dose methotrexate is a moderately effective, well tolerated regimen in patients with SCCHN but does not seem superior to the combination of carboplatin and fluorouracil only.
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PMID:Carboplatin, continuous infusion fluorouracil and mid-cycle high-dose methotrexate as initial treatment in patients with locally advanced head and neck cancer. Hellenic Co-operative Oncology Group Study. 178 Oct 38

Based on clinical evidence that prolonged exposure to anti-neoplastic agents may ameliorate dose-limiting toxicity while facilitating anti-tumor activity, we conducted a phase I trial of 14-day continuous intravenous infusion mitoxantrone. Study objectives were to: (1) determine the maximally tolerated dose for phase II trials; (2) determine the incidence and severity of side effects; and (3) study the pharmacokinetics of continuous infusion mitoxantrone. Sixteen patients with drug-resistant advanced cancers were entered into the trial. Three or more patients were treated at each dose level (1.0, 1.25, and 1.5 mg/m2/day) for a total of 33 courses (mean 2.1 courses/patient, range, 1-4). Courses were repeated every 4 weeks. The maximally tolerated dose (MTD) was found to be 1.5 mg/m2/day. At this dose four of six patients had grade III or IV leukopenia (mean WBC nadir 1900/microliters, range, 800-3600/microliters). Other toxicities were grade I or II stomatitis (two patients), grade I diarrhea (one patient), and grade I nausea (one patient). Renal and hepatic toxicity were not observed. No alopecia or infectious complications occurred. Pharmacokinetic studies were performed using high-performance liquid chromatography (HPLC). Steady-state plasma levels at the 1.5 mg/m2/day dose were reached by 48 h, with a mean steady-state plasma concentration of 3.2 +/- 0.7 ng/ml, mean total body clearance of 340 +/- 79 ml/min/m2, and mean area under the plasma disappearance curve (AUC) of 955 +/- 185 micrograms h/l. No responses were observed, although no patients with mitoxantrone-sensitive tumors were treated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A phase I trial of 14-day continuous intravenous infusion mitoxantrone. 180 19

Nineteen patients with non-small cell lung cancer (eight patients with adenocarcinoma, nine patients with squamous cell carcinoma, one patient with large cell carcinoma and one patient with sarcoma) who had not received previous chemotherapy were treated with a combination of adriamycin (30 mg/m2, i.v., on day 1), cisplatin (80 mg/m2, i.v., on day 1) and etoposide (70 mg/m2, i.v., on day 1-5). This chemotherapy regimen was repeated as long as possible for patients in whom PR was induced. Among all patients, CR was induced in none and 6 showed a PR (response rate 32%). However, 4 (56%) squamous cell carcinoma patients also showed PR. The median response duration in 6 PR patients was 28 weeks, and the median survival time in all patients was also 28 weeks. Mild to severe hematologic toxicities were induced and one patient died during myelosuppression. However almost all cases were reversible. Other toxicities included alopecia, nausea/vomiting, diarrhea, stomatitis, peripheral neuropathy and myocardial infarction which were reversible and manageable. The APVp therapy may be a valuable regimen for non-small cell lung cancer, especially squamous cell carcinoma.
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PMID:[Adriamycin, cisplatin and etoposide combination chemotherapy in non-small cell lung cancer]. 184 90

Fifty-two women with advanced breast cancer were treated with 6 cycles of epirubicin. Even though the study was started with a dose schedule of 110 mg/m2 every 3 weeks, the average treatment interval was 26 days and the median weekly dose 78% of the protocol requirement. Forty-eight patients were evaluable for response; 3 achieved a complete remission which lasted for 17, 24 and 65 weeks, respectively, and 14 a partial remission. Median survival was 32 weeks. Toxicity included nausea/vomiting (68%), anemia (24%), leukopenia (37%), thrombocytopenia (8%), alopecia (81%), stomatitis (24%), diarrhea (14%), fever (19%) and fatigue (14%). Also 1 treatment-related death occurred and 2 cases of arrhythmia. Monotherapy with high doses of epirubicin has definite activity in advanced breast cancer and deserves further study in combination with hematopoietic growth factors which might allow a higher dose intensity.
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PMID:High-dose epirubicin as a single agent in the treatment of patients with advanced breast cancer. A Hellenic Co-operative Oncology Group study. 186 51

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

Ten patients with non-resectable gastric cancer were subjected to a neo-adjuvant chemotherapy (FLEP therapy), consisting of 4 drugs (leucovorin and 5-FU i.v., CDDP and etoposide i.a.) combination therapy from August 1989 to April 1991. The response rate of this therapy with primary lesions, metastatic lymph-nodes (mainly paraaortic lymph nodes), metastatic liver tumor and peritoneal dissemination were 50, 50, 25 and 33%, respectively. Five cases underwent total gastrectomy. Pathological evaluation of these cases was Grade 1 or 2. Side effects were mainly gastrointestinal disturbances, namely stomatitis, nausea, vomiting and anorexia, along with bone marrow suppression. Performance status of these patients improved to a significant degree by the therapy. This therapy seemed to be effective in controlling paraaortic lymph-node metastasis. The advantage of i.a. delivery was investigated by Tc-MAA scintigraphy. The distribution of Tc-MAA after i.a. injection suggested that i.a. chemotherapy enhanced intraabdominal drug concentration. There is no established treatment for far advanced cases, so this therapy seems to be worth a try.
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PMID:[Evaluation of effective neo-adjuvant chemotherapy (FLEP therapy) in the treatment of advanced gastric cancer]. 187 15

Because of the synergy seen in adult trials when 5-fluorouracil is combined with leucovorin, we initiated a Phase I trial of this combination in children's refractory cancer. Leucovorin, an equal mixture of the (6R,S)-diastereoisomers, was administered p.o. for 6 consecutive days as 4 equal doses at 0, 1, 2, and 3 h totaling 500 mg/m2/day. 5-Fluorouracil was given daily on days 2 to 6 as an i.v. bolus immediately following the last dose of leucovorin. The leucovorin dose was held constant while the 5-fluorouracil dose was escalated in cohorts of patients from 300 mg/m2/day to its maximally tolerated dose. Thirty-five patients (19 with acute leukemia and 16 with solid tumors) were evaluable for toxicity. The maximally tolerated dose of FUra was 450 mg/m2/day for 5 treatments for patients with solid tumors and 650 mg/m2/day for 5 treatments for the children with leukemia. The dose-limiting toxicities were myelosuppression and stomatitis. Other side effects included transient, mild elevations of serum transaminases, mild nausea, vomiting, and diarrhea. The pharmacokinetics of high-dose p.o. leucovorin was studied in 23 children. There was considerable interpatient variability in the plasma concentrations of total bioactive folates (TBAF), (6S)-leucovorin, and (6S)-5-methyltetrahydrofolic acid. The maximum plasma concentration (Cmax) of TBAF was 821 +/- 97 (SE) nM, occurring at a median of 8 h; the Cmax of (6S)-leucovorin was 77 +/- 11 nM, occurring at 4 h. The TBAF concentration fell to 146 +/- 42 nM by 24 h. (6S)-5-Methyltetrahydrofolic acid accounted for 90 +/- 7% of the TBAF at the Cmax. The plasma concentration of (6R)-leucovorin, the unnatural isomer, was equal to that of TBAF. Thus, p.o. leucovorin reduced the 5-fold excess of (6R)-leucovorin over TBAF seen after i.v. doses. The relative amounts of the three major plasma species were approximately the same as in adults, even though the Cmax of each compound was lower.
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PMID:Pharmacology and phase I trial of high-dose oral leucovorin plus 5-fluorouracil in children with refractory cancer: a report from the Children's Cancer Study Group. 189 77

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

To assess the efficacy and tolerance of fluconazole in the treatment of oesophageal candidiasis, 47 AIDS patients with this infection were enrolled in an open prospective study using fluconazole 100 mg given orally once daily. Clinical cure was obtained in all of 41 evaluable patients, with confirmation of cure in all of 31 patients who underwent post-treatment oesophagoscopy. Forty patients were followed up for at least 30 days; none suffered a relapse of oesophagitis but seven had a recurrence of stomatitis which was effectively treated with fluconazole. Fluconazole was well tolerated. Nausea was noted in three patients one of whom interrupted therapy. Transient mild elevation of ALT/AST was noted in five of 41 patients (12%). Fluconazole appears to be a safe and effective agent for oral therapy of oesophageal candidiasis associated with AIDS.
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PMID:Efficacy of oral fluconazole in the treatment of AIDS associated oesophageal candidiasis. 191 85


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