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)

Altretamine is a National Cancer Institute-designated group C antineoplastic agent used in the treatment of advanced ovarian cancer. Altretamine is a highly lipid-soluble drug available only for oral administration as a capsule. The drug is activated through metabolic oxidation to intermediate methylol derivatives and formaldehyde. It is unclear which metabolite is the major species responsible for cytotoxicity or the primary mechanism of cytotoxicity. As a single agent in the treatment of ovarian cancer, altretamine demonstrates a response rate similar to other active agents in this disease (21-39 percent). The major utility of altretamine is in combination with other agents such as cyclophosphamide, doxorubicin, fluorouracil, melphalan, and cisplatin. However, few randomized trials have evaluated the contribution of altretamine in these multiagent combinations. Dose-limiting toxicities include gastrointestinal (nausea, vomiting, anorexia), hematologic, and neurotoxic (peripheral neurotoxicity). The therapeutic role of altretamine is limited because of a toxicity profile similar to that of cisplatin, one of the more active agents in ovarian cancer. Its use should be reserved for patients who are not candidates for more standard platinum-based regimens.
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PMID:Altretamine. 190 41

An early Phase II study of CTP-11, a new derivative of Camptothecin, in gynecologic cancers was carried out by a cooperative study group of 9 institutions. Forty-six patients were enrolled, and there were 14 cases of ovarian cancers, 7 of cervical cancer, 6 of uterine body cancers and 1 of endometrial stromal sarcoma which satisfied study criteria. The response rate in ovarian cancers was 21.4%, and in cervical cancers 42.9%, among an overall rate of 21.4%. Three out of 6 patients with objective response had undergone previous chemotherapies including cisplatin, suggesting that CPT-11 was effective for patients with no response or refractory to these therapies. Leukopenia was a major adverse reaction with an incidence of 60.0% (grade 2 or more). Gastrointestinal symptoms such as nausea vomiting, anorexia and diarrhea were frequently observed (grade 2 or more; 13.3-43.3%). These were generally tolerable except in a few cases. Besides these reactions, alopecia was also observed (33.3%), but severe adverse reactions such as nephropathy were not. These results suggested that CPT-11 was effective against ovarian cancer and cervical cancer. The recommended dose regimen for a late phase II study is considered to be 100 mg/m2 once weekly and 150 mg/m2 once every 2 weeks.
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PMID:[An early phase II study of CPT-11 in gynecologic cancers. Research Group of CPT-11 in Gynecologic Cancers]. 201

Treatment options for patients with ovarian cancer who have failed systemic and intraperitoneal (ip) cisplatin-based chemotherapy are limited. We conducted a phase I clinical study of ip thiotepa in patients with refractory ovarian cancer to determine the maximum tolerated dose (MTD). Ten patients were given 39 courses of thiotepa (median number of courses per patient, 3.5; range, 1-10+). All patients had received prior ip cisplatin; 7 also had received iv cisplatin, and 5 had three or more prior regimens. Thiotepa (30-80 mg/m2) was given ip in 2 liters normal saline every 4 weeks. The therapy was well tolerated. There was no vomiting, stomatitis, alopecia, or peritonitis. The dose-limiting toxicity was myelosuppression. With repeated doses, patients had a delayed marrow recovery and required a 1- to 2-week delay in treatment. Six patients had stable disease (duration 2-14+ months; median duration 5 months); 1 patient had a 50% decrease in CA-125 level, and 1 patient with no measurable disease remained clinically disease-free. In summary, ip thiotepa had clinical activity in heavily pretreated patients with refractory ovarian cancer with disease stabilization seen in 6 of 9 evaluable patients and a partial response seen in 1 patient. Myelosuppression was the only toxicity encountered. A dose of 60 mg/m2 ip is recommended for phase II studies.
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PMID:A phase I clinical trial of intraperitoneal thiotepa for refractory ovarian cancer. 210 79

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.
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PMID:Intraperitoneal lymphokine-activated killer-cell and interleukin-2 therapy for malignancies limited to the peritoneal cavity. 221 99

In prospective alternative crossover test, we confirmed significant superiority of a three-drug combination of clonazepam (C) lorazepam (L) and dexamethasone (D) to (L) and (D) to control vomiting induced by 50 mg/m CDDP containing chemotherapy for gynecological malignancies (p less than 0.001). Vomiting frequency in initial 24 hours was 2.28 +/- 2.21 and 6.00 +/- 3.80 times a day respectively. According to this result, clonazepam, dexamethasone, metoclopramide and diphenhydramine (B) were used as a second regimen to control the vomiting in 80 mg/m CDDP containing chemotherapy for ovarian cancer patients. Clonazepam (2 mg 2 times p.o. -4 and 0 hrs before CDDP drip), dexamethasone (8 mg 5 times iv from -3 hrs each 3 hrs), metoclopramide (2.5 mg/kg iv loading from -2 hrs with 0.4 mg/kg/hr continuous infusion for 9 hrs) and diphenhydramine (30 mg/body 2 times im -2.6 hrs) were chosen to control CDDP-induced nausea and vomiting. These four drugs (C+L+D+B) prominently inhibited the chemo-induced vomiting up to 0.44 +/- 1.50 times a day, and 87.5% of courses was completely satisfactory.
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PMID:[Evaluation of antiemetic effect of clonazepam, metoclopramide, dexamethasone and diphenhydramine for prevention of cisplatin-induced vomiting]. 238 45

When used as first-line treatment for advanced ovarian cancer in phase III trials, single-agent carboplatin has produced clinical complete response rates comparable with or exceeding those of single-agent cisplatin. Phase I/II trials of combination chemotherapy have yielded overall objective response rates of 44% to 75% when carboplatin was combined with either cyclophosphamide or chlorambucil. In randomized phase III trials of carboplatin combination chemotherapy, response rates similar to those of cisplatin combinations have been achieved but with greatly reduced toxicities. The data from these phase I, II, and III trials show that carboplatin is as active as cisplatin in patients with advanced ovarian cancer and is associated with a significantly lower incidence and is associated with a significantly lower incidence of emesis, ototoxicity, peripheral neuropathy, and renal dysfunction. Thus, carboplatin should be considered the platinum compound of choice in the firstline treatment of advanced ovarian cancer.
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PMID:Carboplatin in the first-line chemotherapy of ovarian cancer. 240 22

A prospective phase II study was performed to evaluate the effect and tolerability of a peroral combination chemotherapy consisting of hexamethylmelamine, cyclophosphamide, and carmofur in patients with epithelial ovarian cancer previously heavily treated by cisplatin-based chemotherapy but no longer responding to it. Of the 27 patients 1 showed a clinical complete remission lasting 15+ months and 4 a partial remission of 6+ to 21 months. A further 7 patients had an unchanged situation of 4 to 13+ months. The median survival of the nonresponders was 3 months. The side effects were tolerable, mostly nausea and vomiting. Only 4 of 27 patients suffered from severe vomiting causing discontinuation of the therapy. The peroral ambulatory chemotherapy prolonged markedly the overall survival of about one-half of the patients with ovarian cancer who previously failed to respond to cisplatin-based chemotherapy.
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PMID:Phase II evaluation of peroral carmofur, cyclophosphamide, and hexamethylmelamine as a second-line therapy in advanced epithelial ovarian carcinoma. 250 Mar 86

Carboplatin, a new cisplatin analogue, appears as active as cisplatin in patients with advanced ovarian cancer, but in phase I and II trials has proven significantly less toxic. In single-agent phase II trials, carboplatin has been associated with clinical complete response (CR) rates of up to 13% and overall objective response rates of up to 32% in patients with prior cisplatin exposure. As first-line treatment in phase II trials, single-agent carboplatin has produced clinical CR rates ranging from 9% to 62% and overall objective response rates of 45% to 85%. In phase III trials in this patient population, single-agent carboplatin has been associated with clinical CR rates comparable with or exceeding those of single-agent cisplatin. Phase I/II trials of combination chemotherapy have yielded overall objective response rates of 44% to 75% when carboplatin was combined with either cyclophosphamide or chlorambucil. In randomized phase III trials of combination chemotherapy, response rates similar to those of cisplatin have been achieved. However, toxicities were greatly reduced in the carboplatin-treated patients. The data from these phase I, II, and III trials document that carboplatin is as active as cisplatin in patients with advanced ovarian cancer and is associated with a significantly lower incidence of emesis, ototoxicity, peripheral neuropathy, and renal dysfunction. Thus, carboplatin may become the platinum compound of choice in the first-line treatment of advanced ovarian cancer.
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PMID:Carboplatin in the treatment of ovarian cancer. 265 95

Twenty-three previously untreated ovarian cancer patients were treated, from January 1986 to March 1987, with combination chemotherapy consisting of cisplatin, cyclophosphamide and cytarabine (DAC regimen). All patients had advanced disease, which included 18 stage III and 5 stage IV patients. Sixteen patients had serous, 6 undifferentiated and 1 mixed histotype. Surgery consisting of total abdominal hysterectomy, bilateral salpingo-oophorectomy, partial omentectomy and appendicectomy was performed in only 11/23 patients. Seventeen patients had bulky disease when the treatment was started. Four courses of chemotherapy were initially administered to all patients; second look laparotomy was performed in patients with no clinically measurable disease or with presumable entirely resectable tumor. Vomiting was the major side effect of chemotherapy: myelotoxicity was mild and in only one patient permanent renal damage occurred. A total of 14 objective clinical responses (73.7%) were observed, of which 9 were complete (47.4%). Six clinical complete remissions (37.5%) occurred in the group of patients with bulky disease. At second-look laparotomy six patients were found disease free (26%), 4 of whom originally had bulky disease (25%). Short-term DAC regimen seems to be a very effective treatment, with acceptable toxicity, in patients with ovarian cancer.
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PMID:The adjuvant treatment of ovarian cancer: result of the pilot study of a new combination chemotherapeutic regimen (DAC). 268 May 9

Corynebacterium parvum was administered intraperitoneally to 21 patients with epithelial ovarian cancer. Nineteen patients had surgically measurable disease and two received adjuvant therapy. Surgically confirmed responses were documented in six of 19 patients (31.6%), with two complete responses (10.5%) and four partial responses (21.1%). Three patients (15.8%) had stable disease, and 10 patients (52.6%) had disease progression. The mean survival of the patients who had a complete response was 35.5 months; the four patients who had a partial response the mean survival was 26.6 months, and of the nonresponders the mean survival was 12.6 months (p less than 0.02). The mean survival of the entire group was 18.2 months. Initial response and patient survival correlated with the amount of disease pretreatment. Thus six responding patients had less than or equal to 5 mm maximum diameter tumors, that is, minimal residual disease. Toxicity in the 86 courses of therapy included abdominal pain in 78% of cases, fever in 56%, nausea in 40%, and vomiting in 22%. Stimulation of cytotoxic lymphocytes resulted from the administration of C. parvum, which induced a significant increase of both intraperitoneal natural killer lymphocyte cytotoxicity and antibody-dependent cell-mediated cytotoxicity in six of nine patients tested; these two types of cytotoxicity correlated with response to therapy and may be partially responsible for the surgically documented tumor regression. While the clinical usefulness of intraperitoneal C. parvum is limited because of its toxicity, intraperitoneal immunotherapy may prove useful in patients with minimal residual ovarian cancer when more refined agents become available.
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PMID:Intraperitoneal immunotherapy of epithelial ovarian carcinoma with Corynebacterium parvum. 299 76


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