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)

During the 9-year period from 1982 to 1991, 72 patients with melanoma were treated with a 5-day quadruple drug chemotherapy regime (BELD) comprising bleomycin, vindesine (Eldesine), CCNU (Lomustine) and DTIC. Forty-three patients had stage III melanoma, 34 of whom had evaluable disease. Of these 34, six (17.6%) achieved a complete response (CR), eight (23.5%) had a partial response (PR), five (14.7%) had stabilized disease (SD) and 15 (44.1%) had progressive disease (PD). Overall median survival of stage III melanoma patients was 38 weeks. Median survival of responders (CR + PR) was 47 weeks and 21 weeks for non-responders (SD + PD) (P < 0.005). Median follow-up time was 38 weeks. Following these encouraging results, 30 patients with stage II melanoma received BELD chemotherapy as adjuvant therapy after regional node dissection and clearance. Adjuvant BELD chemotherapy did not alter survival in these patients. BELD combination chemotherapy is well-tolerated, the main problems being nausea, vomiting, and leucopenia. We have maintained a combined response rate (CR + PR) of 41.1% for stage III disease. This is comparable with other combination chemotherapy regimes, which have as yet not been superseded by the newer biological therapies.
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PMID:Nine years' experience of BELD combination chemotherapy (bleomycin, vindesine, CCNU and DTIC) for metastatic melanoma. 128 72

We conducted a phase I study of CI-898 (trimetrexate), a new diaminoquinazoline antifolate in 22 patients with solid cancer in a multicenter collaborative study. The dosage schedule was single-dose intravenous administration (single treatment), followed by one or two courses of 5-day intravenous administration (5-day treatment) at 3-week intervals. Starting at 2 mg/m2 (1 n), the dose was increased up to 15 mg/m2 (7.5 n) for single treatment and 12 mg/m2 (6 n) for 5-day treatment. Evaluable cases numbered 18 for single treatment and 17 for 5-day treatment. In single treatment, the highest dose of 15 mg/m2 caused no serious side effect and did not reach the maximum tolerated dose (MTD). In 5-day treatment, leukocytopenia and thrombocytopenia were found dose dependently, the dose-limiting factor was bone marrow depression, and MTD was 10 mg/m2/day. The leukocyte and platelet counts reached the nadir in 1-3 weeks after initiation of 5-day treatment. The recovery from the nadir required about one week. Subjective side effects included mucitis (mouth, anus), malaise and gastro-intestinal symptoms (nausea, anorexia, diarrhea). None of alopecia, cardiotoxicity and nephrotoxicity were found. In the present phase I study, a tendency of tumor reduction was found in one case each of breast cancer (adenoma) and lung cancer (squamous cell carcinoma). The plasma concentration of the unchanged compound after single treatment showed a biphasic elimination pattern (t1/2 alpha 0.8-1.4 hr, t1/2 beta 9.4-13.0hr). The urinary excretion of the unchanged compound was 14.7-23.5% of the administered dose. In 5-day treatment, no accumulation was found. From the results of the present study, the recommended dosage of CI-898 in the early phase II study was considered to be 8 mg/m2/day intravenously for 5 days (every 3-4 weeks).
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PMID:[Phase I study of CI-898. CI-898 Study Group]. 183 40

Fifteen patients with metastatic malignant melanoma, including 10 who had not previously received systemic therapy, were treated with recombinant alpha2-interferon (IFN-alpha 2) in a dose of 20 million IU/m2 by 30-min i.v. infusion daily for 5 days each 14 days. Evaluable metastatic sites included lung, subcutaneous tissue, liver, nodes, adrenals, and bone. Subjective toxicity was generally mild to moderate, with fever (38.2-40.2 degrees C), occasional rigors, fatigue, myalgia, headache, and nausea. Objective toxicity included transient neutropenia and elevation of hepatic enzymes, particularly gamma-glutamyl transpeptidase. In 1 of the 10 patients receiving more than one cycle, IFN dosage was reduced because of toxicity, but later reescalated. All patients were evaluated for response. No overall partial or complete responses were observed, but two site responses (lung and subcutaneous tissue) were seen. Median survival from start of IFN treatment was 19 weeks. High doses of IFN were reasonably well tolerated in this study, but the results suggest little activity against malignant melanoma.
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PMID:Phase-II study of recombinant alpha 2-interferon in advanced malignant melanoma. 287 Nov 16

The possible synergism of cisplatin (P) and 5-fluorouracil was studied in 38 consecutive patients with advanced or metastatic colorectal carcinoma. Cisplatin 60 mg/m2 i.v.q. 4 weeks and fluorouracil 600 mg/m2 i.v. weekly were administered for at least 2 cycles, on an out-patient basis, to 24 males and 14 females with a median age of 57 years and a median PS of 80 (Karnofsky). Evaluable lesions were: primary unresectable tumor in 2 patients, local recurrence in 11, liver, lung, bone and soft tissue metastases in 21, 7, 2 and 3 patients respectively. With a median number of 3 cycles administered to 35 evaluable patients, 6 partial responses, 16 unchanged and 13 progressions were observed. Responses were observed in the liver (2 patients), lungs (1) and soft tissues (3). Median remission duration was 15 weeks, median duration of 'unchanged' was 12 weeks. The overall median survival was 24 weeks (30.5 weeks for responders and 22.5 weeks for non-responders). Six patients were pretreated with chemotherapy not containing cisplatin (mainly adjuvant 5-FU). None of them responded. Toxicity was very tolerable with moderate nausea, vomiting and alopecia in the majority of the patients; bone marrow toxicity was generally mild with no blood transfusions required, no complications of myelosuppression (sepsis or bleeding) and no chemotherapy-related deaths. In this experience the combination of low dose cisplatin with fluorouracil, does not appear to significantly enhance 5-FU toxicity and the response rate is not superior to that reported with 5-FU alone. However, better designed schedule combinations with optimal doses, sequences and exposure time of the 2-drug regimen, seem necessary to obtain the biochemical events that support the potentiation.
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PMID:Cisplatin and 5-fluorouracil combination chemotherapy in advanced and/or metastatic colorectal carcinoma: a phase II study. 365 87

The clinical pharmacology and toxicity of a novel anthracycline derivative, 4'-O-tetrahydropyranyladriamycin (THP-adriamycin), was investigated in patients with advanced malignant diseases. The starting dose was 30 mg/m2 which was escalated by increments of 10 mg/m2. Twelve patients with a median age of 42 (range, 19-69) years and a median Eastern Cooperative Oncology Group performance score of 2 (range, 1-2) were entered into the study. The diagnoses included four testicular cancers, two breast cancers, two small cell lung cancers, two acute myeloid leukemias, one colon cancer, and one hemangiosarcoma. THP-adriamycin was given as an i.v. bolus injection every 3 weeks. Evaluable were 18 courses for general toxicity, 16 courses for hematological toxicity, and 16 courses for pharmacokinetics. THP-adriamycin had a short initial half-life of 1.4 +/- 0.3 min (mean +/- SD) due to rapid cellular uptake. Peak concentrations in unseparated blood cells were reached 5 min after drug injection and remained higher than in plasma throughout the observation period of 72 h. The half-lives of THP-adriamycin in plasma were 19 +/- 2.8 min in an intermediate and 13 +/- 1.6 h in the terminal phase. A linear correlation was observed between the dose and the areas under the concentration curves for THP-adriamycin in plasma (r2 = 0.97) and blood cells (r2 = 0.99). The volume of distribution was 2124 +/- 221 liters/m2 and the total clearance rate 115 +/- 11 liters/m2h. THP-adriamycin was metabolized to Adriamycin, THP-adriamycinol, and adriamycinol. The major metabolite was Adriamycin with a terminal half-life in plasma of 33 +/- 10 h. The area under the curve of Adriamycin was also correlated to the administered dose (r2 = 0.96). Since excessive peak concentrations of Adriamycin were avoided, the treatment with THP-adriamycin might be an alternative to continuous infusions or weekly administrations. The maximum tolerated dose was 70 mg/m2, and the dose-limiting toxicities were leukopenia and thrombocytopenia. Anemia, nausea, and vomiting were mild to moderate, and no other toxicity was observed. All side effects were dose dependent and reversible. In a patient with breast cancer, a disease stabilization was achieved lasting for 9 weeks. No objective remission was observed. We suggest 60 mg/m2 in pretreated or poor risk and 70 mg/m2 in untreated or good risk patients every 3 weeks for further clinical trials.
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PMID:Clinical pharmacology and toxicity of 4'-O-tetrahydropyranyladriamycin. 381 48

Antiemetic effects of perphenazine and prochlorperazine, both administered by continuous i.v. infusion after a loading dose, were compared in patients receiving cisplatin. Study subjects were 6 men and 13 women for whom other antiemetic therapy had failed; each patient was studied during two courses of cisplatin therapy. Patients were randomly selected to receive either perphenazine or prochlorperazine during the first course; for the second course, each received the other antiemetic. During drug administration, nausea, retching, vomiting, and side effects of the antiemetic were recorded hourly by the patient and concurrently by a pharmacist observer (both blinded). Each patient's scores on nausea, retching, and vomiting were compared by drug and by treatment sequence. Evaluable data for 17 patients showed that aggregate differences between responses to the two drugs were not significant. Fourteen patients had significantly less nausea, retching, and vomiting during the second course of treatment. Few side effects were reported. Nervousness was experienced with prochlorperazine in four patients and perphenazine in one, and drowsiness occurred with prochlorperazine in four patients and perphenazine in three. Perphenazine and prochlorperazine, when given in equal doses and administered by continuous i.v. infusion after a loading dose, were equally effective in controlling nausea and vomiting associated with cisplatin therapy.
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PMID:Antiemetic effect of perphenazine versus prochlorperazine intravenously before cisplatin therapy. 636 17

Studies previously performed in our laboratory demonstrated synergistic cytotoxicity and DNA strand break formation in human tumor cells following exposure to a combination of bromodeoxyuridine and bleomycin. Synergy was evident when bromodeoxyuridine was administered prior to or simultaneously with bleomycin and occurred over a wide range of concentration ratios. We therefore undertook a phase I clinical trial of the combination of iododeoxyuridine (IdUrd) and bleomycin to determine the maximally tolerated dose of IdUrd that could be administered with a standard dose of bleomycin and to determine the toxicities of the combination. Eligible patients were those with advanced cancer refractory to standard therapy who had a performance status of 0-2, measurable or evaluable disease, and adequate organ function. IdUrd was administered as a 5-day continuous i.v. infusion beginning at a dose of 250 mg/m2/day with escalation in cohorts of 3-6 patients according to a modified Fibonacci scheme. Bleomycin was administered at a dose of 15 mg/m2/day as a continuous i.v. infusion during the last 3 days of the IdUrd infusion. Cycles of therapy were repeated every 28 days. Plasma levels of IdUrd and iodouracil were determined by high performance liquid chromatography. Thirty patients received a total of 79 cycles of IdUrd/bleomycin. Dose-limiting toxicity was bone marrow suppression. At the maximally tolerated IdUrd dose of 2780 mg/m2/day, the median neutrophil nadir after the first cycle of therapy was 805/microliters and the median platelet nadir was 48,000/microliters. Other toxic effects included mucositis, fatigue, nausea, diarrhea, fever, and skin toxicity. Plasma steady-state concentrations of IdUrd increased proportionally to administered IdUrd dose. IdUrd clearance varied from 0.253 liters/min/m2 to 0.503 liters/min/m2 and did not correlate with IdUrd dose. IdUrd dose and concentration correlated significantly with granulocyte and platelet nadirs, and a pharmacodynamic model for white blood cell count nadir could be defined by pretreatment white blood cell count, IdUrd dose, and gender. The recommended IdUrd dose for phase II testing of this combination is 2140 mg/m2/day. Phase II studies will be of particular interest in those diseases, such as carcinomas of the head, neck, and esophagus, where bleomycin has documented activity as a single agent.
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PMID:Phase I clinical and pharmacological study of iododeoxyuridine and bleomycin in patients with advanced cancer. 768 Feb 82

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is an effective drug in the treatment of metastatic breast cancer (MBC). In the salvage setting, 5-fluorouracil (5-FU) and folinic acid have proved to be effective against MBC as well. Recent preclinical data suggest that paclitaxel plus 5-FU has additive cytotoxicity. Given these observations, we initiated a phase II trial in which 38 women with MBC have been treated with a combination of all three drugs. All patients are currently evaluable for toxicity and 34 are evaluable for response. All women had histologically proven and assessable disease. Patients with prior exposure to paclitaxel were ineligible. Patient characteristics include a median age of 51 years (age range, 31 to 73 years) and a median performance status of 1 (range, 0 to 2). Thirty-three patients have received prior chemotherapy, of whom 23 had adjuvant chemotherapy only. Fifty-eight percent of the patients (22 of 38) had received prior doxorubicin or mitoxantrone; four patients had only hormonal therapy. Four patients had bone-only disease, and three patients had lymphangitic spread or cytologically positive pleural effusion as the only evaluable disease. Treatment consisted of paclitaxel 175 mg/m2 over 3 hours (day 1 only), followed by folinic acid 300 mg over 1 hour, followed by 5-FU 350 mg/m2 on days 1 to 3. Patients received standard paclitaxel premedications. To date, 175 cycles have been administered (median cycle length, 29 days; median number of cycles per patient, five). Toxicities included grade 3/4 infections in nine cycles (5%), grade 3/4 mucositis in three cycles, grade 3/4 nausea/vomiting in three cycles, grade 1 paresthesias in 12 patients (32%), alopecia 100%, and 17 cycles (10%) associated with dose reduction. Based on Cancer and Leukemia Group B toxicity criteria, arthralgia/myalgias were modest and graded mild (32 cycles), moderate (nine cycles), or severe (two cycles). There were two major hypersensitivity reactions, prompting removal of those patients from further protocol treatment. Four patients are unassessable for response due to hypersensitivity reactions (two) and unevaluable disease (two). Among the 34 patients evaluable for response, there were three complete responses, 18 partial responses, one minor response, nine stable disease, and three progressive disease (response rate, 62%). Responses were seen in patients who had received prior doxorubicin or mitoxantrone (11 of 22 patients) and in anthracycline/naive patients (10 of 16 patients). Responses were observed in all metastatic sites: soft tissue, viscera, and bone. Paclitaxel/5-FU/folinic acid appears to be an effective and well-tolerated outpatient regimen for women with MBC, even after failure of anthracycline-containing therapy.
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PMID:Paclitaxel and 5-fluorouracil in metastatic breast cancer: the US experience. 862 38

A Phase I study of the novel angiogenesis inhibitor TNP-470 was performed. Patients with inoperable recurring or metastatic squamous cell cancer of the cervix with evaluable disease, no coagulopathy, and adequate renal, hepatic, and hematological function were eligible. One course of treatment consisted of an i.v. infusion of TNP-470 over 60 min every other day for 28 days, followed by a 14-day rest period. The starting dose was 9.3 mg/m2. Eighteen evaluable patients were treated, with a median age of 48 years (range 27-55) and performance status Zubrod 1 (range 0-2). Grade 3 neurotoxicities consisting of weakness, nystagmus, diplopia, and ataxia were encountered in two patients receiving the 71.2 mg/m2 dose. An intermediate dose level of 60 mg/m2 was evaluated and found to be well tolerated by three patients. Only one patient experienced grade 3 nausea on the 60 mg/m2 dose level. No myelosuppression, retinal hemorrhage, weight loss, or significant alopecia were observed. One patient had a complete response, which continues for 26 months, and three patients with initially progressive disease stage had stable disease for 5, 7.7, and 19+ months. Other Phase I studies, including over 200 patients, were performed concurrently with this study. Based on this experience, the dose of TNP-470 recommended for further studies is 60 mg/m2 as a 60-min i.v. infusion every Monday, Wednesday, and Friday. Neurotoxicity was dose limiting, but appears to be reversible. Otherwise, the treatment was well tolerated. The drug may be active in squamous cell cancer of the cervix. Further studies of TNP-470 in squamous cell cancer of the cervix are warranted.
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PMID:A phase I study of TNP-470 administered to patients with advanced squamous cell cancer of the cervix. 981 36

High-dose megestrol acetate has been reported to be effective salvage therapy for women with ovarian carcinoma. The Eastern Cooperative Oncology Group performed this phase II study of oral megestrol acetate, 200 mg four times daily until disease progression, in 33 patients either with stage III or IV histologically confirmed ovarian carcinoma or with unresectable tumor in the pelvis with measurable or evaluable disease who progressed after treatment with one prior chemotherapy regimen. Thirty and 31 patients were evaluable for response and toxicity, respectively. No patient had an objective response and none had subjective improvement after a median treatment period of 1.4 months. Nausea or vomiting occurred in most patients, usually grade 1-2. Megestrol acetate is ineffective salvage therapy for patients with inoperable, previously treated ovarian carcinoma.
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PMID:High-dose megestrol acetate in the treatment of patients with ovarian cancer who have undergone previous treatment: Eastern Cooperative Oncology Group Study PD884. 985 56


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