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)

Marcellomycin is a new anthracycline that was proposed for clinical trials on the basis of experimental data suggesting reduced potential for hematologic and cardiac toxicity as compared to conventional anthracyclines. This phase I trial was designed to determine the maximum tolerated dose of marcellomycin at a single-dose schedule. The drug was given as a 15-to 30-min i.v. injection. Eighteen patients with a variety of solid tumors received a median of 2 courses (range: 1-5) at doses of 5-60 mg/m2. Myelosuppression was dose-limiting and somewhat unpredictable. It was characterized by early thrombocytopenia and late leukopenia. It occurred at doses greater than or equal to 40 mg/m2 and resulted in a few cases of infection and hemorrhage. Nausea, vomiting and stomatitis were frequent and occasionally severe. Other common non-hematological toxic effects consisted of local phlebitis and fatigue. Electrocardiographic changes were also encountered. Hair loss was rare and negligible. No antitumor activity could be detected. It appears that phase II trials should be preferably restricted to ambulatory patients and that a dose schedule of 50 mg/m2 repeated every 3 weeks may be proposed for this favorable patient population.
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PMID:Clinical phase I trial of marcellomycin with a single-dose schedule. 668 82

The pharmacology, chemistry, pharmacokinetics, clinical studies, and adverse effects of amsacrine, an investigational antineoplastic agent, are reviewed. Amsacrine's mechanism of action is not clearly understood, although the drug is known to inhibit DNA synthesis. As an investigational NCI "Group C" agent, amsacrine is available to physicians for the treatment of adult patients with refractory acute nonlymphocytic leukemia (ANLL) under an established protocol. Following intravenous administration, amsacrine has a biphasic plasma clearance. It is extensively metabolized by the liver to inactive compounds that are excreted in the bile. Phase I studies indicated that amsacrine was potentially effective in patients with solid tumors and acute leukemias. Patients with solid tumors could tolerate much lower doses of amsacrine than leukemia patients because of dose-limiting bone-marrow suppression in the former. In Phase II studies, amsacrine appeared effective in treating the acute leukemias, with response rates of 31% and 23% for acute lymphocytic leukemia and ANLL, respectively. Patients with other types of cancers have not responded to amsacrine therapy. Frequently occurring adverse effects of amsacrine include leukopenia and thrombocytopenia in patients with solid tumors; nausea, vomiting, and diarrhea; mucositis in patients receiving higher doses (leukemia patients); alopecia; hepatotoxicity; and phlebitis. The clinical usefulness of amsacrine appears limited to treatment of the acute leukemias. Studies of combination therapies that include amsacrine are currently underway and should further define the therapeutic role of amsacrine.
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PMID:Review of amsacrine, an investigational antineoplastic agent. 676 91

A phase II study of KW2083 [7-N-(p-Hydroxyphenyl)-Mitomycin C], a derivative of Mitomycin C, was carried out in 20 patients with carcinoma of the lung and in 19 patients with metastatic pulmonary tumor. KW2083 was administered by single intravenous injection at a dose of 20-30 mg/m2 weekly or a single 70 mg/m2 dose. Patients treated with a dose of 20-30 mg/m2 should be given at least 3 doses for eligibility. Of 17 evaluable patients with carcinoma of the lung (11 adenocarcinomas, 3 squamous cell carcinomas, 2 small cell carcinomas and 1 large cell carcinoma), two patients with adenocarcinoma showed a partial response (11.8%). Two patients who achieved PR had adenocarcinoma without prior therapy received KW2083 at a single dose of 70 mg/m2 Objective response rates were 18.2% for 11 patients with adenocarcinoma and 25% for 8 patients with adenocarcinoma treated with a single dose of 70 mg/m2 of 15 evaluable patients with metastatic pulmonary tumor, no patients showed any objective responses. The hematologic toxicities were thrombocytopenia (less than 5 X 10(4)/mm3, 41.6%) and leukocytopenia (less than 2000/mm3, 28.1%); it was observed in 19% of the patients, that thrombocytopenia continued for more than 6 weeks after stopping therapy. Gastrointestinal symptoms such as anorexia (81%), nausea (66%) and vomiting (16%) were severe in patients treated with a single dose of 70 mg/m2. Fever in 19%, alopecia in 13%, phlebitis in 9%, eruption in 6%, stomatitis in 6% and liver insufficiency in 13% were also observed.
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PMID:[Phase II study of KW2083 [7-N-(p-hydroxyphenyl)-mitomycin C] in patients with carcinoma of the lung and metastatic pulmonary tumor]. 688 1

alpha-1,3,5-Triglycidyl-s-triazinetrione (TGT) is a triepoxide derivative with alkylating properties discovered by random screening. TGT has been found to be active against a wide variety of murine tumors, including a P388 subline resistant to cyclophosphamide. The starting dose in this phase-I study was 30 mg/m2 as a single dose IV, repeated every 3-4 weeks, increasing up to 2,700 mg/m2. Severe dose-limiting toxicity took the form of phlebitis becoming apparent a few days after treatment. This was initially seen at the 480 mg/m2 dose level, and was observed with increasing frequency and intensity at higher dose levels. Leukopenia occurred regularly at dose levels above 1,800 mg/m2 and resulted in life-threatening leukopenia in one patient, and in a toxic death at 2,700 mg/m2 in another patient. Other toxic side-effects included moderate reversible thrombocytopenia, nausea, and vomiting. It is recommended that further trials with TGT await the development of more water-soluble formulations or of other triepoxide derivatives.
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PMID:Phase-I study of alpha-1,3,5-triglycidyl-s-triazinetrione (NSC 296934). 688 26

Twenty-three patients with advanced solid tumors received 9-hydroxy-2N-methyl-ellipticinium acetate at a single daily i.v. dose of 15-80 mg/m2 for 5 consecutive days, repeated every 3 weeks. One partial and one minor response were achieved in two patients with breast cancer. Dryness of the mouth was dose-related and dose-limiting. Local phlebitis was also dose-related and frequently severe at the highest dose levels. Other non-hematologic toxic effects were essentially mild to moderate and included nausea, vomiting, diarrhea, stomatitis, fever, weakness, transient renal and hepatic impairment, alopecia and chest pain. Minimal myelosuppression was encountered. It appears that 60 mg/m2/day is the maximum tolerated dose with a five-day schedule. According to our findings, this schedule does not seem to offer any advantage over the previously tested weekly administrations.
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PMID:Phase I clinical study of 9-hydroxy-2N-methyl-ellipticinium acetate (NSC-264137) administered on a 5-day i.v. schedule. 688 28

AMSA, an acridine derivative with significant antitumor activity in experimental tumors, was administered to 17 patients with advanced tumors refractory to standard chemotherapies. A phase I study was undertaken in 10 patients with solid tumors and lymphomas. Dose-limiting toxicity was myelosuppression. With a median dose of 90 mg/m2 (75-148 mg/m2), median lowest WBC count was 1,000/mm3 (100-3,200) on day 11 and its recovery up to 4,000/mm3 was seen on day 21, while lowest platelet count was 42 X 10(3)/mm3 (7-300 X 10(3) on day 12 and its recovery up to 100 X 10(3)/mm3 was on day 20. Non-hematological toxicities were nausea (39%), vomiting (11%) and phlebitis (17%) in 18 courses of therapy. The result indicated that the recommended dose schedule for a phase II evaluation was 90 mg/m2, every three weeks. Therapeutic activity was observed in patients with non-Hodgkin's lymphoma (one partial response and two minor responses out of four). Two out of five breast, one ovarian, and one melanoma patients showed stable diseases. Five leukemic patients (three AMLs, one MoL, and one blastic CML) were treated with AMSA, and in these cases cytoreduction of peripheral and bone marrow blasts was seen, but it was not adequate to induce remission. Further clinical trials with this agent are warranted, especially in patients with acute leukemia, lymphoma and breast cancer.
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PMID:[Phase I-II studies of a new antineoplastic agent, 4'-(9-acridinylamino)-methanesulfon-m-anisidide (AMSA)]. 689 58

Forty-six patients with inoperable cancer and leukemia in relapse were given vindesine (VDS) either by iv bolus weekly at doses ranging from 2.0 to 5.5 mg/m2 or by 24-hour continuous infusion weekly at doses ranging from 1.0 to 7.0 mg/m2 of estimated body surface area. VDS was well-tolerated by patients with normal liver function who had previously been minimally treated with myelosuppressive agents at a dose of less than or equal to 4 mg/m2 either by iv bolus or by 24-hour infusion weekly. The dose-limiting toxic effects of VDS were leukopenia and neurotoxicity. Leukopenia was cumulative but easily reversible by interruption of weekly dose. Neurotoxicity was insidious and hardly reversible. Patients with liver dysfunction appeared to develop more neurotoxicity. Other toxic effects included a decrease in hemoglobin level, transient hepatic dysfunction, cellulitis or phlebitis at the iv site, stomatitis, nausea, and vomiting. Degrees and parameters of toxic effects observed after iv bolus and 24-hour infusion of the same doses were indistinguishable except for an increased incidence of local cellulitis in the infusion group.
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PMID:Initial clinical study with vindesine: tolerance to weekly iv bolus and 24-hour infusion. 692 28

In a Phase I trial patients with advanced malignant melanoma were treated with high-dose nitrogen mustard (HN2) and autologous bone marrow transplantation. Three patients were entered into the protocol. After procurement of 1.1--5.5 x 10(5) committed stem cells (CFU-C) per kg body wt, 33 mg/m2 of HN2 was administered i.v. as a bolus. Forty-eight hours later the noncryopreserved bone marrow was reinfused i.v. Side effects consisted of nausea, vomiting, anorexia, alopecia, phlebitis, hepatotoxicity, and neurotoxicity. Cardiotoxicity and hypocalcemia were encountered as unanticipated side effects not described so far by using lower dosages of HN2. Granulocytopenia of less than 10 x 10(9)/l and thrombocytopenia of less than 50.0 x 10(9)/l lasted for a mean of 10 and 8 days, respectively. Measureable disease present in two of three patients did not respond to the dose of HN2 used in this protocol. This study shows that hematologic recovery was shorter than previously reported in studies using HN2 without autologous bone marrow transplantation. The nonhematologic side effects of this dose of HN2, however, were severe and preclude the use of higher doses.
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PMID:High-dose nitrogen mustard (HN2) with autologous nonfrozen bone marrow transplantation in advanced malignant melanoma. A phase I trial. 701 56

Etoposide is a semisynthetic podophyllotoxin derivative with a broad spectrum of antitumor activity and a relatively high therapeutic index. The synergism in animal with cis-platinum, cyclophosphamide, BCNU, and cytosinarabinoside is interesting for combination regimen. Mechanisms of action are inhibition of nucleoside transfer and of DNA and RNA synthesis, single stranded breaks, inhibition of protein synthesis and of microtubular assembly. While in lower concentrations etoposide is acting cell-cycle-dependent with accumulation of cells in the G2-phase it has, in high concentrations, also a cellcycle-phase-unspecific lethal effect. Most suitable is the oral and i.v. application of etoposide in fractionated doses of 80--120 mg/m2 on 3--5 consecutive days and repetition after 21 [14--28] days. Side effects are dose-limiting bone marrow toxicity, nausea, vomiting, fever, hypotension, phlebitis, mucositis, neuropathy, cardiotoxicity, alopecia. Etoposide is one of the most active single agents in small-cell bronchus carcinoma with a remission rate of 37% (10% CR), and is very active in NHL (36%), testicular carcinoma (37%), AMML (35%), choriocarcinoma (35%), and neuroblastoma (29%). The role of etoposide in combination with other active drugs in these tumors is currently investigated in bronchus and testicular carcinoma and NHL, where etoposide will belong to the drugs of the first choice in the future.
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PMID:[Etoposide VP 16--213)--a podophyllotoxinderivative with high antitumor activity (author's transl)]. 703 50

A variety of agents are used as premedication for upper gastrointestinal endoscopy (U.G.E.). To our knowledge, no double blind studies have been performed to compare their value. In this study phenoperidine (2 mg i.v.) was compared with diazepam (t mg i.v.) in 200 consecutive patients undergoing elective U.G.E. The study was randomized and double blind in regard to both endoscopists and patients. All patients were given atropine (0.4 mg i.v.) and a throat spray with 2% amethocaine. Patients who needed supplemental medication were given diazepam and excluded from final analysis. A graded questionnaire was recorded by endoscopists and patients after U.G.E., and a further anonymous questionnaire was returned by patients four days later. Statistical analysis revealed that phenoperidine was superior at facilitating intubation and providing more relaxation as judged by the endoscopist. Patient questionnaires, four days after U.G.E., indicated less distress during intubation and examination with phenoperidine. Nausea, vomiting, amnesia and phlebitis were uncommon after either phenoperidine or diazepam.
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PMID:A comparison of diazepam and phenoperidine in premedication for upper gastrointestinal endoscopy: a randomized double blind controlled study. 704 71


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