Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fluorouracil (5-FU) and cisplatin display marked therapeutic synergy in preclinical models and are effective in the treatment of a number of solid tumors when combined and administered intravenously (IV). Each drug has also been administered intraperitoneally (IP) and displays a favorable pharmacologic profile and acceptable clinical toxicity. We therefore undertook a phase I study to determine the feasibility and toxicity of combination IP chemotherapy with these agents. Thirty-one patients with histologically documented malignancy confined to the peritoneal space were treated with cisplatin 90 mg/m2 mixed with 5-FU in 2 L of lactated Ringer's solution and given IP for 4 hours every 28 days. Cohorts of at least three patients received starting 5-FU concentrations ranging from 5 mmol/L (1,300 mg in 2 L) to 20 mmol/L. The dose-limiting toxicity was neutropenia with a median granulocyte nadir of 156 cells per microliter occurring at a 5-FU dose of 20 mmol/L. Intrapatient escalation of the 5-FU dose was permitted and 15 cycles of chemotherapy were delivered at 5-FU concentrations greater than 20 mmol/L, the highest concentration being 30.7 mmol/L (8 g of 5-FU in 2L). Other toxicities included mild to moderate nausea during all cycles of therapy, vomiting in 54% of cycles, and diarrhea in 15% of cycles. Abdominal pain, renal dysfunction, peripheral neuropathy, and oral mucositis occurred infrequently and were not related to the 5-FU dose. Peritoneal fluid and plasma 5-FU concentrations were measured by high-performance liquid chromatography (HPLC) in selected patients. Mean peak plasma 5-FU concentrations ranged from 6.19 mumol/L to greater than 60 mumol/L, and peritoneal fluid to plasma 5-FU area under the curve (AUC) ratios ranged from 85 to 1,150. Nine of 15 patients with nonbulky disease had resolution of malignant ascites or at least a 50% reduction of peritoneal studding by tumor at repeat laparotomy. We conclude that combination IP chemotherapy with cisplatin and 5-FU is technically feasible and has acceptable clinical toxicity and a favorable pharmacologic profile. The recommended starting 5-FU dose for phase II trials is 3,900 mg mixed with 90 mg/m2 of cisplatin in 2 L of isotonic fluid.
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PMID:Phase I clinical and pharmacologic study of intraperitoneal cisplatin and fluorouracil in patients with advanced intraabdominal cancer. 223 Aug 97

Intra-arterial hepatic chemotherapy (IAHC) with adriamycin (ADM) has not increased its therapeutic index. For our preclinical studies, we selected pirarubicin (THP), an ADM derivative with faster cellular uptake. In rabbits with VX2 tumor in the liver we compared plasmatic and cellular pharmacokinetics of ADM and THP after i.v. and IAH therapy. For ADM, there were no differences in plasma and heart concentrations, with only a slight increase in tumoral levels after IAH compared to i.v. administration; on the other hand, with IAH THP, there was important reduction in systemic exposure with a major increase in tumoral drug distribution. In the phase I study, involving nine patients with implanted catheters, the starting dose of THP was 30 mg/m2 with a 10 mg/m2 intrapatient escalation every 3 weeks in the absence of toxicity. Pharmacokinetics were compared for i.v. and IAH administration in seven patients. The limiting toxicity was neutropenia and the maximal tolerated dose (MTD) ranged from 50 to 110 mg/m2. Moderate nausea-vomiting (grade 1-2) and alopecia (grade 1) occurred at the MTD. No arterial occlusion, gastroduodenal ulcer, hepatitis, or sclerosing cholangitis were seen. In the phase II study, in colorectal cancer patients (CRC) with metastasis confined to the liver, patients were enrolled until June 1990. THP (40 min infusion every 3 weeks) was initiated at 60 mg/m2 with 10 mg/m2 increment until grade 2 hematotoxicity. The median MTD was 85 mg/m2 (range of 60-120 mg/m2), and the median number of cycles was 7 (range of 2-11) with cumulated doses from 180 to 1,030 mg/m2. Grade 2-4 neutropenia was reached in 15 patients. Other toxicities included two arterial occlusions, one episode of gastritis, but no hepatic toxicity and no heart failure. Antitumor effect (in 18 patients) included 1 CR, 5 PR, 3 MR, 6 NC, and 3 PD. The median survival was 18+ months and 1-year survival was 73% +/- 12%. Seven patients had extrahepatic progression at this time. In conclusion, besides 5-FU or Fudr, THP is active in IAHC (probably in relation with high local extraction) on CRC liver metastases usually unresponsive to ADM. It can be given in an outpatient setting with minimal toxicity.
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PMID:Intra-arterial hepatic chemotherapy with pirarubicin. Preclinical and clinical studies. 229 52

Seven patients with acute myeloid leukemia (AML) in first complete remission were treated with escalating high doses of cyclophosphamide, etoposide, and cytosine arabinoside (Ara-C). In all patients autologous bone marrow preservation was performed prior to therapy. Bone marrow was stored in blood bags in a refrigerator for 48-72 h at 4 degrees C and then reinfused over a central line. All patients had a full hematological recovery. The mean time of neutropenia (neutrophils less than 500/microliters) was 14 days (range 9-24 days), and the mean time of thrombocytopenia (platelets less than 20,000/microliters) was 9 days (range 7-11 days). The nonhematological toxicity was tolerable with mild to moderate nausea/vomiting, mucositis and diarrhea, and so far not dose-limiting. Six patients remain in complete remission 17+, 9+, 5+, 5+, 4+, and 1+ months after autotransplantation. One patient relapsed 8 months after autotransplantation. High-dose chemotherapy with noncryopreserved bone marrow autotransplantation may be useful as intensified consolidation for patients with AML in first complete remission.
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PMID:High-dose chemotherapy with noncryopreserved autologous bone marrow transplantation for acute myeloid leukemia in first complete remission. 232 69

The toxic effects and tissue uptake of both cisplatin and oxaliplatin--[(1R, 2R)-1,2-cyclohexanediamine-N,N'] [oxalato(2-)-O,O']platinum--were previously shown to vary similarly according to dosing time in mice. A 4-hour infusion of cisplatin resulted in fewer side effects and allowed administration of higher doses at 16 hours than at 4 hours in patients with cancer. We hypothesized that the continuous venous infusion of oxaliplatin for 5 days would be less toxic and would deliver a higher dose to the patient if the drug were infused at a circadian rhythm-modulated rate (peak at 16 hr; schedule B) rather than at a constant rate (schedule A). We tested this hypothesis in a randomized phase I trial. We escalated the dose of oxaliplatin to the patient by 25 mg/m2 per course. Courses were repeated every 3 weeks. An external, multichannel, programmable-in-time pump was used for the infusions. Toxicity was assessable for 94 courses in 23 patients (12 patients with breast carcinoma, nine with hepatocellular carcinoma, and two with cholangiocarcinoma). The incidence of neutropenia of World Health Organization grades II-IV and the incidence of distal paresthesias were 10 or more times higher (P less than .05) with schedule A than with schedule B. In addition, vomiting was 55% higher (P = .15) with schedule A than with schedule B. Furthermore, with schedule B, the mean dose of oxaliplatin (P less than .001) and its maximum tolerated dose (P = .06) could be increased by 15% over those doses with schedule A. An objective response was achieved in two of the 12 patients with previously treated breast cancer. We recommend that the dose of oxaliplatin for phase II trials be 175 mg/m2, delivered according to the circadian rhythm-modulated rate.
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PMID:Phase I trial of 5-day continuous venous infusion of oxaliplatin at circadian rhythm-modulated rate compared with constant rate. 234 69

Fifteen dogs with relapsed lymphoma were treated with doxorubicin and dacarbazine (ADIC) to reinduce remission. All the dogs' lymphomas had become resistant to prior therapy with doxorubicin alone. Five of the 15 dogs had a complete response to the first treatment with ADIC, and three had partial responses. Of the eight dogs receiving a second cycle, two had complete responses, and one had a partial response. One dog that received a third ADIC treatment no longer responded. The median survival time from the first ADIC treatment for all dogs was 45 days (range, 18-241 days). The five dogs having complete responses to the first ADIC treatment had a median survival time of 105 days (range, 45-241 days) after this treatment. Toxicity due to ADIC treatment was acceptable and did not exceed that seen when doxorubicin was given as a single agent. The treatment resulted in severe neutropenia in three dogs. One dog died due to neutropenic sepsis. Vomiting, diarrhea, and anorexia occurred, but were tolerable, resulting in hospitalization in only one instance. ADIC is apparently a useful chemotherapeutic combination to reinduce remission in some dogs with relapsed lymphoma.
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PMID:Treatment of relapsed canine lymphoma with doxorubicin and dacarbazine. 240 65

Although consequences of zinc deficiency have been recognized for many years, it is only recently that attention has been directed to the potential consequences of excessive zinc intake. This is a review of the literature on manifestations of toxicity at several levels of zinc intake. Zinc is considered to be relatively nontoxic, particularly if taken orally. However, manifestations of overt toxicity symptoms (nausea, vomiting, epigastric pain, lethargy, and fatigue) will occur with extremely high zinc intakes. At low intakes, but at amounts well in excess of the Recommended Dietary Allowance (RDA) (100-300 mg Zn/d vs an RDA of 15 mg Zn/d), evidence of induced copper deficiency with attendant symptoms of anemia and neutropenia, as well as impaired immune function and adverse effects on the ratio of low-density-lipoprotein to high-density-lipoprotein (LDL/HDL) cholesterol have been reported. Even lower levels of zinc supplementation, closer in amount to the RDA, have been suggested to interfere with the utilization of copper and iron and to adversely affect HDL cholesterol concentrations. Individuals using zinc supplements should be aware of the possible complications attendant to their use.
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PMID:Zinc toxicity. 240 97

Standard chemotherapy for disseminated germ cell tumors (GCT) cures most patients but causes considerable acute toxicity, including treatment-related death due to septicemia during neutropenia and pulmonary fibrosis. In addition, chronic and delayed toxicities, particularly Raynaud's phenomenon, have been reported in 6% to 37% of treated patients. In an attempt to minimize the acute and chronic effects of treatment which are related primarily to vinblastine and bleomycin, a randomized trial comparing the efficacy and toxicity of vinblastine + bleomycin + cisplatin + cyclophosphamide + dactinomycin (VAB-6) and etoposide + cisplatin (EP) was conducted on 164 eligible patients with good-prognosis GCT. Seventy-nine of 82 (96%) patients receiving VAB-6 and 76/82 (93%) receiving EP achieved a complete remission (CR) with or without adjunctive surgery. Similar proportions of patients in both arms were found at surgery to have necrosis/fibrosis or mature teratoma. With a median follow-up of 24.4 months in the VAB-6 arm and 25.9 months in the EP arm, the total, relapse-free, and event-free survival distributions were similar in the two arms. Patients receiving EP experienced less emesis (P = .05), higher nadir WBC (P = .06) and platelet counts (P = .01), less magnesium wasting (P = .0001), less mucositis (P = .09), and no pulmonary toxicity. No treatment-related mortality was observed. EP is an efficacious and less toxic regimen and is recommended for good-prognosis patients with disseminated GCT.
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PMID:A randomized trial of etoposide + cisplatin versus vinblastine + bleomycin + cisplatin + cyclophosphamide + dactinomycin in patients with good-prognosis germ cell tumors. 245 57

We designed a phase II study to determine whether induction chemotherapy (CT) consisting of leucovorin, vincristine, methotrexate, doxorubicin, and cyclophosphamide (LOMAC) followed by high-dose intensification chemotherapy (ICT) with cyclophosphamide, thiotepa, and autologous stem cell rescue (ASCR) could increase the complete response (CR) rate and survival in women with stage IV breast cancer. Twenty-nine women were enrolled on study; 16 patients had received prior adjuvant chemotherapy and no patient had received chemotherapy for stage IV disease. Two patients were found to be ineligible and excluded from further analysis. Of the 27 patients treated, four (15%) obtained a CR and 15 (56%) a partial response (PR) after LOMAC induction, for an overall response rate of 70%. Of the 22 patients treated with ICT, 12 patients had a CR, and nine were in PR after induction and converted to CR after ICT. The toxicities included nausea/vomiting, mucositis, diarrhea, dermatitis, alopecia, and infections secondary to neutropenia. The 1-year survival is 60%; the median has not yet been reached. The time to treatment failure for patients on study is 10 months. The treatment approach of ICT and ASCR following induction chemotherapy can lead to an improved CR rate in stage IV breast cancer. How this increased CR rate leads to a prolonged disease-free survival requires further follow-up.
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PMID:High-dose consolidation therapy with autologous stem cell rescue in stage IV breast cancer. 251 Dec 76

The effect of the addition of radiosensitizers to low-dose total-body irradiation was studied. SR2508 (1 g/kg) or misonidazole (0.35 g/kg) was given 30 min prior to single-dose total-body irradiation, delivered at 0.1 Gy/min. Six dogs received either SR2508 or misonidazole and 2 Gy irradiation, and 14 dogs served as controls, receiving no drug and either 2 or 3 Gy of total-body irradiation. All dogs had a decline in their white blood cell and platelet counts and were supported with prophylactic antibiotics and platelet transfusions. High plasma levels of both radiosensitizers were achieved. The degree of cytopenia with 2 Gy total-body irradiation when combined with either radiosensitizer was not significantly greater than that seen with 2 Gy alone, and the neutropenia was significantly less than that seen with 3 Gy alone. The only observed toxicity of the drugs was vomiting, which started shortly after the infusion of SR2508 and before the radiation treatment. A single high-dose infusion of a radiosensitizer combined with total-body irradiation appears to cause a mild increase in bone marrow toxicity but is otherwise well tolerated.
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PMID:Bone marrow toxicity of total-body irradiation combined with radiosensitizers. 253 59

Based on the independent activity of cisplatin, vinblastine, and dimethyl-triazeno-imidazole-carboxamide (DTIC) (CVD), a combination of these agents was used in the treatment of patients with advanced melanoma. Vinblastine was used in a dose of 1.6 mg/m2/d for 5 days, DTIC was used in a dose of 800 mg/m2 intravenously (IV) on day 1, and cisplatin was used in a dose of 20 mg/m2/d for 4 days starting on day 2 of chemotherapy. The courses of chemotherapy were repeated at 3-week intervals. All patients were premedicated with antiemetics, and IV hydration was used before cisplatin. Fifty-two consecutive patients were registered and 50 were evaluable for response. Two patients achieved a complete response (CR) and 18 patients had a partial response (PR) for an overall response rate of 40% (95% confidence interval, 27% to 55%). The median duration of response was 9 months and the median survival time of the responders was 12 months. The overall median survival time of patients treated on this protocol was 9 months. The treatment was associated with significant toxicity consisting of nausea, vomiting, diarrhea, and partial hair loss. Additionally, neutropenia with a median nadir granulocyte count of 500/microliters was observed, and significant anemia required blood transfusions in a majority of the patients after three to four courses of chemotherapy. The dose-limiting toxicity was peripheral neuropathy which required discontinuation of cisplatin after six to eight courses of chemotherapy. We believe that this triple-drug regimen has significant activity that appears to be superior to the single-agent activity of these drugs, both in terms of increased response rate and duration of response.
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PMID:A prospective evaluation of a triple-drug regimen containing cisplatin, vinblastine, and dacarbazine (CVD) for metastatic melanoma. 280 90


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