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

A phase I multicenter evaluation of a novel antiestrogen, toremifene, was undertaken in postmenopausal women with various advanced difficult-to-treat malignancies. One hundred and seven women were treated at one of six dosage levels (10, 20, 40, 60, 200, or 400 mg/d orally) for at least 8 weeks. Weekly evaluations for toxicity were conducted. The most common side effects were nausea (31%), vomiting (12%), and hot flashes (29%). Five patients were removed from the study for possible adverse reactions: three patients experienced hypercalcemia; one experienced tremulousness, fatigue, and inability to think clearly; and one had vaginal bleeding. Twelve patients died while on study, 11 with disease progression and one with a pulmonary embolus. Sex hormone-binding globulin (SHBG) levels increased and there was a modest decline in serum antithrombin III levels. Four of 48 assessable patients had partial responses: three with breast cancer and one with endometrial cancer. Toremifene was generally well tolerated at the doses tested.
 ...
PMID:Phase I study of toremifene in patients with advanced cancer. 183 8

Both single-agent cisplatin and the combination of doxorubicin and cyclophosphamide demonstrated moderate activity against endometrial carcinoma in earlier salvage trials. Since January 1979, 102 patients with advanced primary (n = 42) or recurrent (n = 60) endometrial carcinoma were prospectively treated with cisplatin (50 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2) (PAC). PAC was administered monthly until disease progression or toxicity precluded additional therapy. Patients received a median of five treatment cycles (range 1-13). Of the 87 patients with measurable disease, 12 had a complete clinical response, while 27 had a partial clinical response, for an overall objective response rate of 45%. No differences in response rates between primary and recurrent disease patients were noted. Median time to response was 2.5 months with a median response duration of 4.8 months. Nonresponders included 33 patients with stable disease and 15 with progression. Median progression-free survival for all patients was 6 months. Dose escalation was possible in 25% of patients; however, 52% of patients required dose reductions during treatment. Clinically significant toxicities included neutropenia (65%), anemia (47%), emesis (21%), nephrotoxicity (17%), and neurotoxicity (4%). Our study indicates that endometrial cancer is significantly responsive to PAC. Enthusiasm for this regimen should be tempered by the limited duration of response and substantial treatment toxicity.
 ...
PMID:Prospective treatment of advanced or recurrent endometrial carcinoma with cisplatin, doxorubicin, and cyclophosphamide. 201 51

Toremifene is a triphenylethylene derivative structurally and pharmacologically similar to tamoxifen. This Phase I trial assessed the safety, pharmacokinetics, anti-estrogenic, and estrogenic effects of toremifene at six dose levels (10, 20, 40, 60, 200, and 400 mg/day). The most common side-effects associated with therapy included gastrointestinal (nausea/vomiting 43%), anti-estrogenic (hot flashes 29%), and CNS (dizziness/vertigo 12%). Three patients with bone metastases from breast cancer developed hypercalcemia. At doses greater than or equal to 40 mg/day a decline in LH and FSH occurred which was not statistically significant. At all doses tested SHBG rose during therapy. A dose dependent estrogenic blockade was seen on the vaginal epithelium following challenge with transdermal estradiol. Steady-state concentrations of toremifene were reached within 4 weeks, and at doses greater than or equal to 60 mg/day ranged from 879-3445 ng/ml. The half-life was found to be 5 days, and at three weeks following discontinuation of treatment concentrations greater than 24 ng/ml were detected. The N-desmethyl and 4-hydroxy metabolites achieved steady state levels within 4 weeks and had half-lives of 6 and 5 days respectively. Partial responses were seen in 4 patients, 3 with breast cancer treated at 200 mg/day and 1 with endometrial cancer treated at 400 mg/day.
 ...
PMID:Phase I study of the tolerance and pharmacokinetics of toremifene in patients with cancer. 214 80

A phase II study of the effectiveness and toxicity of carboplatin in the treatment of metastatic or locally advanced endometrial cancer was carried out by the Southwest Oncology Group. Thirty-two patients were registered in the study and 23 were fully evaluable for response and toxicity. Carboplatin was administered in a dose of 400 mg/m2 at 28-day intervals without concomitant hydration if blood counts had recovered sufficiently. There were seven responses (two complete and five partial responses) among the 23 evaluable patients, for an overall response rate of 30%. Four (two of two complete responders and two of five partial responders) of the seven responding patients remain alive at 839+ to 987+ days from the start of therapy. The two complete responders and one of the partial responders had small-volume disease, which may have contributed to their prolonged survival. Myelosuppression was the most prominent toxicity encountered. Seventeen of 27 patients evaluable for toxicity developed platelet counts of less than 75 X 10(3)/muL during therapy, but no hemorrhagic complications were encountered. Leukopenia was less prominent, with only nine of 27 patients developing white blood cell counts of less than 3.0 X 10(3)/microL. No important nephrotoxicity or neurotoxicity was observed. Emesis occurred in ten of 27 patients but was not dose-limiting. No unexpected toxicities were encountered. Carboplatin appears to be an active agent in the treatment of endometrial carcinoma.
 ...
PMID:Carboplatin therapy in advanced endometrial cancer. 217 83

Autologous lymphokine-activated killer (LAK) cells and recombinant human interleukin-2 (rIL-2) were administered intraperitoneally (IP) to 24 patients with malignancies limited to the peritoneal space. Ten patients had ovarian cancer, 12 had colorectal cancer, and one patient each had endometrial carcinoma and primary small-bowel adenocarcinoma. All ovarian cancer patients, three of twelve colorectal cancer patients, and one patient with endometrial carcinoma had received prior therapy. Patients received IL-2 100,000 U/kg every 8 hours intravenously (IV) for 3 days, and 2 days later underwent daily leukapheresis for 5 days. LAK cells were generated in vitro by incubating the peripheral blood mononuclear cells in IL-2 for 7 days and were then administered IP daily for 5 days through a Tenckhoff catheter (Davol, Inc, Cranston, RI) together with IL-2 25,000 U/kg IP every 8 hours. All but one patient completed at least one cycle of therapy. Toxic side effects included minor to moderate hypotension, fever, chills, rash, nausea, vomiting, abdominal pain and distension, diarrhea, oliguria, fluid retention, thrombocytopenia, and minor elevations of liver function tests; all of these rapidly improved after discontinuation of IL-2. One patient had a grand mal seizure, and one suffered a colonic perforation; these were felt to be treatment-related. IP fibrosis developed in 14 patients and limited repeated cyclic administration of this therapy in five patients. Two of 10 (20%) ovarian cancer patients and five of 12 (42%) colorectal cancer patients had laparoscopy- or laparotomy-documented partial responses. We conclude that LAK cells and rIL-2 can be administered IP to cancer patients, resulting in moderate to severe short-term toxicity and modest therapeutic efficacy. Further investigation of this form of adoptive immunotherapy modified to address the problem of IP fibrosis and with lower IP IL-2 doses is justified by these initial results.
 ...
PMID:Intraperitoneal lymphokine-activated killer-cell and interleukin-2 therapy for malignancies limited to the peritoneal cavity. 221 99

Four patients with recurrent or advanced endometrial cancer have undergone combination chemotherapy with Cyclophosphamide, Adriamycin and Cisplatin (CAP). All drugs were administered by I.V. on day 1 in the following doses: Cyclophosphamide 500 mg/m2, Adriamycin 50 mg/m2 and Cisplatin 50 mg/m2. The treatment was repeated every 4 weeks and continued as long as there was disease progression. Two complete clinical responses and two partial responses were achieved. Based on these good results, we have initiated post-operative prophylactic chemotherapy using CAP in high risk patients. Adverse effects including myelo-suppression, nausea, and vomiting, and alopecia were seen in almost all patients. In no case, however, did any patient experience life-threatening toxicity. Based on our experience, CAP therapy appears tolerable when used per our schedule.
 ...
PMID:[Combination chemotherapy using cyclophosphamide, adriamycin, and cisplatin in recurrent or advanced endometrial cancer--a preliminary report]. 292 85

To evaluate the role of hexamethylmelamine (HMM) in the treatment of endometrial cancer, 20 women with metastatic or recurrent endometrial carcinoma received HMM orally at a dose of 8 mg/kg/day. Six patients (30%) showed a partial response, with a median duration of response of 3.5 months and a range of 1 to 7 months. Two patients responded to HMM as a second-line agent following previous treatment with nonhormonal chemotherapy. There were no complete responses. The major toxicities noted with HMM therapy were nausea, vomiting, and neurotoxicity. In 6 patients (30%), therapy with HMM was discontinued because of toxicity. Although HMM is active against endometrial cancer when given at a dose of 8 mg/kg/day, it appears to have limited usefulness because toxicity precludes its prolonged administration.
 ...
PMID:Hexamethylmelamine chemotherapy for disseminated endometrial cancer. 679 Oct 63

THP-ADM is a new antitumor antibiotic which belongs to the anthracycline group. This agent was administered to 42 histology proven various malignant disease patients with a schedule of 60-80 mg per body (40-55 mg per m2) iv bolus, every three weeks. THP-ADM administration revealed mild upper GI toxicity (vomiting 19%, stomatitis 21%) and leukopenia (less than 2,000 per mm3) in 80% and thrombocytopenia (less than 60,000 per mm3) in 38% with good rebound. There was no signs or symptoms of cardiac failure including the patient who had received 740 mg per body (500 mg per m2). Definite response (CR, PR) was observed in ovarian carcinoma 4/11, cervix carcinoma 2/7, breast carcinoma 1/6, malignant lymphoma 5/5 and mesothelioma 1/2. Furthermore, some response (MR) was observed in lung metastasis from endometrial carcinoma 2/4, and stomach carcinoma 1/3. The above indicated usefulness of this agent and further study should be continued, especially a controlled study with adriamycin.
 ...
PMID:[Preliminary phase II clinical study of 4'-O-tetrahydropyranyl doxorubicin (THP-ADM)]. 688

Twenty-six women with advanced or recurrent endometrial cancer were treated with cisplatin at a dose of 50, 70, or 100 mg/m2 every 4 weeks. An objective response was obtained in 11 of 26 patients (42%), with 10 partial responses and 1 complete response. The median duration of remission was 5 months, with a range of 2 to 11 months. The complete response lasted 8 months. Five patients had stable disease lasting an average of 5 months. One of 6 patients (16.6%) responded to cisplatin at a dose of 50 mg/m2, 4 of 7 (57%) responded to the dose of 70 mg/m2, and 6 of 13 (46%) responded to the dose of 100 mg/m2, but the differences were not statistically significant (P = .2). In 8 of 26 cases (31%) cisplatin was discontinued because of toxicity. Three patients developed a peripheral neuropathy, 1 patient refused further therapy because of vomiting, 2 patients had nephrotoxicity, and 2 others had both nephrotoxicity and neurotoxicity. The average total cumulative dose of cisplatin administered when renal deterioration and neuropathy occurred was approximately 500 mg/m2. Cisplatin is definitely active against endometrial cancer, but toxicity precludes its prolonged administration in high doses on an outpatient basis. By maintaining a forced diuresis, toxicity can probably be decreased, thereby permitting continued administration of cisplatin. The drug may also be more useful when used at a lower dose in combination with other active agents against endometrial cancer.
 ...
PMID:Cisplatin chemotherapy for disseminated endometrial cancer. 704 39

Methyl-GAG was given to 71 patients with advanced malignancies as a weekly brief infusion (30-120 minutes) or as a biweekly 24- or 120-hour infusion. Mucositis (stomatitis, pharyngitis, esophagitis, and, rarely, inflammation of other mucous membranes) was dose-limiting in all three schedules. Generalized fatigue, malaise, myalgia, dysesthesias, nausea, and vomiting were more frequent in the brief-infusion schedule. Myelosuppression was mild and not dose-related. Fever, ventricular arrhythmias, skin rash, tender swelling of the palms, neuropathy, and paralytic ileus were rare. Toxicity was increased in patients with renal insufficiency or "third-space" fluid but was not increased by hepatic dysfunction. Cumulative and overlapping toxicity was evident only in the weekly schedule. Higher doses of methyl-GAG were tolerated when the duration of infusion was increased. The recommended doses for phase II trials are 700 mg/m2 weekly as a 1-2 hour infusion, 850 mg/m2/24 hours biweekly, and 1500 mg/m2/120 hours biweekly. Therapeutic effects were seen in all schedules and included objective responses in colon carcinoma (one of 13 patients), renal cell carcinoma (one of nine), and Hodgkin's lymphoma (one of two) and objective improvements in esophageal carcinoma (one of three), endometrial carcinoma (two of two), and leiomyosarcoma (one of three).
 ...
PMID:Methyl-GAG in patients with malignant neoplasms: a phase I re-evaluation. 705 68


1 2 3 Next >>