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)

There is a critical need to find new chemotherapeutic agents that are active in platinum-refractory ovarian cancer. A phase II trial of zeniplatin (CL 286,558), a third-generation platinum compound, was conducted in 31 patients with advanced ovarian cancer to examine the safety and activity of the agent when used as a salvage treatment in individuals previously exposed to organoplatinum-based therapy. In general the drug was well tolerated, with moderate emesis and bone marrow suppression being observed in most patients. An unexpected side-effect was significant fever, of unknown etiology, which was noted in 16% of patients. Out of 20 patients, 2 (10%; 95% confidence intervals: 1%-32%) with clinically defined platinum-refractory disease achieved a partial response. Unfortunately, although we have defined definite but modest activity for zeniplatin in platinum-refractory ovarian cancer, further development of this drug has been discontinued because of the severe renal toxicity observed in other clinical trials of this cytotoxic agent.
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PMID:Phase II trial of zeniplatin (CL 286,558), a new patinum compound, in patients with advanced ovarian cancer previously treated with organoplatinum-based therapy. 842 99

Twenty-two patients with ovarian cancer stage III and IV received combination chemotherapy with CDDP, adriamycin (ADM) and cyclophosphamide (CPM), and were studied for response and side-effects. Patients were divided into two groups according to the following CDDP infusion schedules. (CAP 1) CDDP 7mg/sqm/8 hrs/saline 500 ml/d1-d10, ADM 35 mg/sqm/d1, CPM 350 mg/sqm/d1: 8 cases; (CAP 2) CDDP 70 mg/sqm/2 hrs/d1, ADM 35 mg/sqm/d1, CPM 350 mg/sqm/d1: 14 cases. The overall response rate (CR + PR) was 62.5% in CAP 1, and 50% in CAP 2 (on statistical difference: NS). The 3-year survival rate was 54.7% in CAP 1 and 38.5% in CAP 2 (NS). Side effects of nausea, vomiting and nephrotoxicities were remarkably reduced in CAP 1. These data suggest that lower concentration and longer infusion time of CDDP administration increases the therapeutic index. This infusion schedule is suitable for chemotherapy at home or on an outpatient clinic basis, especially in patients with ovarian cancer.
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PMID:[Increase in CDDP therapeutic index by lower concentration and longer infusion time--home chemotherapy for ovarian cancer]. 843 65

This phase II study was designed to assess the therapeutic potential of intensive course treatment with three anticancer agents: 50 mg of cisplatin on day 1, 40 mg/m2 of epirubicin on day 2, and 250 mg of 5-fluorouracil on days 2 through 5. Drug courses were repeated every 2 weeks and most patients received between 4 and 6 courses. Thirty-five patients with measurable advanced solid cancers entered the study. They consisted of 16 gastric, 5 colorectal, 4 gallbladder, 3 pancreatic, 3 lung, 2 esophageal, 1 uterine, and 1 ovarian cancers. Of the 35 patients, 29 were evaluated for therapeutic effect of the regimen, and the overall response rate was 31.0% (5 CR + 4 PR/29). A 33.3% rate of tumor regression, consisting of 2 complete responses (CR) and 3 partial responses (PR) out of 15 patients (2 CR + 3 PR/15), was seen for gastric cancers. For the other types of tumors the responses were achieved in 2 lung cancers (1 CR + 1 PR/3). 1 uterine cancer (1 CR/1), and 1 ovarian cancer (1 CR/1). The esophageal, colorectal, pancreatic, and gallbladder cancers were unresponsive to this regimen. Toxicities of the drug treatment were clinically tolerable and consisted of general malaise, nausea, vomiting, stomatitis, alopecia, and leucopenia. However, two patients died of uncontrollable metabolic acidosis after 1 and 2 courses, respectively. This intensive course treatment appears to promote the regression of gastric, lung, and gynecologic cancers.
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PMID:A phase II study of 5-fluorouracil, cisplatin, and 4'-epirubicin in the treatment of advanced solid cancers. 845 15

Forty-two patients affected by either stage III and IV ovarian cancer with residual tumor after surgery or recurrent ovarian cancer entered a phase II study of the combination carboplatin 300 mg/m2 and cyclophosphamide 600 mg/m2 every 28 days. Thirty-eight patients were evaluable for response and of these 27 obtained complete or partial remission with a 71% overall remission (clinical complete remission 45%; partial remission 26%). Treatment tolerability was on the whole good. The most frequent side effects were leukopenia (76%), anemia (67%) and nausea/vomiting (60%). Thrombocytopenia was present in 31% of the patients, but nearly always to a mild degree except for one grade 4 case. No other grade 4 side effect was observed. We did not observe any cases of nephrotoxicity and only two patients complained of paresthesia. This carboplatin-cyclophosphamide combination in advanced ovarian carcinoma produces comparable results, in terms of objective responses, to those obtained with standard cisplatin-based regimens, with suggestion of a better toxicological profile.
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PMID:A phase II study of carboplatin and cyclophosphamide in advanced ovarian carcinoma. 845 65

Over the last couple of decades a reduction of estrogen by at least 80% in combined oral contraceptives (OCs) and much research have resulted in effective and safe contraception. We still do not know longterm effects of OCs however. OCs may protect against endometrial and ovarian cancer. A link between current OC use and liver cancer exists in areas where liver cancer is rare. An association between OC use and cervical cancer disappears when researchers control for sexual activity and barrier method use. Some research shows OC use increases the risk of breast cancer, while other research does not. There does appear to be an increased risk of breast cancer developing in women younger than 46 years of age and who have used OCs for at least 10 years. Women who have a preexisting cardiovascular condition and/or smoke should not use OCs. OC progestogens may impair glucose metabolism in healthy women, but just for 6 months. Women with diabetes mellitus can use OCs, but may need to increase insulin intake. OCs can cause hypertension in 4-5% of healthy women and worsen hypertension in about 9-16% of hypertensive women. Progestogen-only OCs have fewer systemic side effects than combined OCs, but often cause menstrual changes. Their long term effects are not yet known. Injectables containing a progestogen cause few, if any, adverse effects. The subdermal implant, Norplant, tends to cause menstrual disturbances, but is safe and effective. Progestogen - only vaginal rings are as effective as progestogen-only OCs, but menstrual irregularities are common. Failure rates for combined vaginal rings match those of combined OCs. Long-term effects of vaginal rings are not known. Postcoital contraception does not cause serious side effects, but may cause vomiting and menstrual irregularities. A levonorgestrel-releasing IUD is effective and reduces menstrual blood loss, sometimes resulting in amenorrhea. Hormonal injections in men are unlikely in the near future.
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PMID:Hormonal contraception. 829 64

Sixty-six patients with ovarian cancer were treated with low-dose consecutive CP (LDC-CP) consisting of cyclophosphamide (CPM: 500 mg/m2, day 1) and CDDP (10 mg/m2, days 1-7). Two-9 (median: 4) courses of LDC-CP were given following reduction surgery (42 cases) or preceding primary debulking (24 cases). Among 66 cases, 12 with stage Ic were not evaluable (NE). The response rate (CR + PR/evaluable) for stages II-IV was 57.4% (12 + 19/54). Histologically, serous and endometrioid type showed a significantly (p < 0.001) higher response rate (77.5% among 40 evaluable) compared to the other histologic type (0% among 14). Toxicities including nausea/vomiting and renal impairment were markedly mild or almost absent despite the lack of any particular care. Grade 3 leucopenia and thrombocytopenia were observed only in 4.2%, and 2.5% of total 284 courses, respectively. Mean survival time by stage was 1,309 days for stage I, 809 days for stage II, 1,180 days for stage III, and 691 days for stage IV, with a significant difference among stages (p = 0.0452). In stages III and IV disease, significant prognostic factors included 1) response to chemotherapy, 2) no. of LDC-CP courses, 3) histologic subtype, 4) performance status, and 5) tumor size. Thus, LDC-CP is considered to be a useful chemotherapeutic regimen for serous and endometrioid type ovarian cancer.
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PMID:[Chemotherapy of ovarian cancer with a combination of low-dose consecutive CDDP and cyclophosphamide]. 849 34

A dose-finding study was performed in 27 ovarian cancer patients to define the maximum tolerated dose of a 3-hour infusion of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in combination with a fixed dose of carboplatin. The median age of the patients was 55 years (age range, 30 to 74 years), the median performance status was 0 (range, 0 to 2), and the sizes of tumors residual to first surgery were identified as > or = 1 cm (14 patients) or less than 1 cm (13 patients). All patients received carboplatin at a fixed dose of 300 mg/m2 over 1 hour. Paclitaxel was administered as a 3-hour infusion at five dose levels, starting at 150 mg/m2 and increasing in 25 mg/m2 increments to 250 mg/m2. In the absence of toxicity, courses were repeated every 4 weeks for a total of six cycles. Mild emesis, general alopecia, and moderate myalgias occurred. Hypersensitivity and cardiotoxicity were observed in 7.4% and 14.8% of patients, respectively. Moderate peripheral neuropathy was experienced by 30% of patients. Grade 3 and 4 neutropenia lasted less than 7 days; no patients required hospitalization for sepsis or febrile neutropenia, and no supportive treatment with granulocyte/granulocyte-macrophage colony-stimulating factor was needed. Twenty-one patients were evaluable for response. Overall response rate (complete response+partial response) was 81%, and responses were observed at all paclitaxel dose levels. The maximum tolerated dose was not achieved. In conclusion, with a fixed dose (300 mg/m2) of carboplatin, paclitaxel can be administered by 3-hour infusion at 250 mg/m2 with manageable toxicity and no supportive care is needed.
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PMID:Pilot study with fixed-dose carboplatin and escalating paclitaxel in advanced ovarian cancer. 855 81

Carboxyamido-triazole (CAI) is a synthetic inhibitor of non-excitable calcium channels that reversibly inhibits angiogenesis, tumor cell proliferation, and metastatic potential. Inhibition of calcium influx and calcium-dependent events is a potential common mechanism underlying these effects of CAI. The cytostatic and antiangiogenic properties of CAI led to its development for clinical investigation. In a Phase I clinical trial open to patients with refractory solid tumors, 49 patients received p.o. administered CAI daily or every other day. Two oral formulations, PEG-400 CAI solution and a gelatin capsule containing CAI in PEG-400, were tested. All administered dosages of CAI yielded plasma concentration at or above the range demonstrated to be effective in inhibiting signaling and cancer progression in vitro and in preclinical models (1 microgram/ml, 2.3 microM). Toxicity of p.o. administered CAI most commonly consisted of dose-related grade 1-2 nausea, vomiting, and occasional anorexia. CAI administration at bedtime ameliorated gastrointestinal complaints in many patients; others required addition of simple antiemetic regimens, usually consisting of metoclopropamide or prochlorperazine. Gastrointestinal complaints were the cause for compliance-limiting toxicity at 175 mg/m2/day of the liquid formulation and 125 mg/m2/day of the gelatin capsule formation. Reversible and rare sensory axonal neuropathy (grade 3, 1 patient) and neutropenia (grade 4, 1 patient) were dose-limiting toxicities observed at the 330 mg/m2 every-other-day liquid CAI dose level. No evidence of cumulative end organ damage or central nervous system injury was observed. Disease stabilization and improvement in performance status was observed. Disease stabilization and improvement in performance status was observed in 49% of evaluable patients who had disease progression before CAI. Disease stabilization and associated improvement in performance status was seen in patients with renal cell carcinoma (7 months), pancreaticobiliary carcinomas (3, 5, and 5 months), melanoma (7 months), ovarian cancer (7 months), and non-small cell lung cancer (3 months). The recommended Phase II doses from this trial are 150 mg/m2/day in the liquid formation and 100 mg/m2/day in the gelatin capsule formation.
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PMID:Clinical investigation of a cytostatic calcium influx inhibitor in patients with refractory cancers. 856 73

A large study of tumors of low malignant potential confirmed the favorable survival in this group of patients compared to invasive epithelial ovarian tumors. Only 8% of patients died with recurrent disease after surgery. Patients with stage IA borderline tumors with mucinous histology tended to recur later and carried a poorer prognosis than patients with serous histology and similar stage. The group at highest risk for relapse were age greater than 70, stage II or III tumors, and histology other than serous. Long-term survival in this group was less than 75%. This high-risk group of patients should be targeted for innovative adjuvant treatment strategies. This year several well-designed studies with large sample sizes showed DNA ploidy to be an important new independent prognostic factor in stage I ovarian carcinoma. In patients with well-differentiated early stage ovarian cancer, DNA flow cytometric analysis may indicate subgroups with less favorable prognostic characteristics. This method of analysis may be beneficial in determining the need for additional treatments after surgery for early stage ovarian carcinoma. Recommendations for the definitive management of early stage ovarian cancer awaits completion of current GOG and European randomized prospective studies. Paclitaxel given in combination with platinum-containing agents is an intense area of research for treatment of advanced stage disease. Early data from a prospective randomized trial of patients with advanced ovarian cancer showed a higher response rate and longer disease-free survival in patients treated with paclitaxel and cisplatin compared to a standard regimen of cyclophosphamide and cisplatin. The impact of this treatment on long-term survival awaits maturation of data. Preliminary results evaluating G-CSF in combination with paclitaxel and cisplatin for dose escalation was reported. Paclitaxel, 250 mg/m2, and cisplatin, 75 mg/m2, were the maximally tolerated doses, with peripheral neuropathy or myalgias the dose limiting toxicities. Further studies are now underway to test the effect of dose-response with escalation therapies and to determine the optimal dose and schedule for the management of patients with advanced ovarian cancer. IL-3 significantly ameliorated neutropenia but did not prevent cumulative platelet toxicity in a regimen utilizing high-dose carboplatin. This mild improvement in myelosuppression was obtained at the cost of significant toxicity. Nausea, vomiting, malaise, bone pain, headache, fever, chills and facial flushing were frequent. Intraperitoneal chemotherapy was tested as a means of consolidation treatment for patients after having a negative second-look laparotomy. These treatments were shown to be feasible; however, prospective randomized trials will be necessary to determine a benefit over operative therapy alone. Several studies addressed to problem of residual disease after primary surgery and adjuvant chemotherapy. A large phase II study conducted by the GOG confirmed the activity of salvage cisplatin-based intraperitoneal chemotherapy in patients with small-volume residual ovarian cancer with favorable pretreatment characteristics. Whether intraperitoneal platinum-based therapy represents an advantage over systemic platinum therapy is being addressed in a prospective SWOG study. The use of six additional cycles of CAP for treatment of residual disease after primary treatment of surgery and adjuvant chemotherapy did not significantly improve complete pathological response and survival. Prolonged duration of chemotherapy above six cycles is not likely to impact treatment for residual disease. A regimen of high dose carboplatin was compared to whole abdominal radiotherapy for treatment of residual disease after initial chemotherapy. There was no difference in survival or disease-free survival between treatments.(ABSTRACT TRUNCATED)
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PMID:Gynecological malignancies. 863 1

Intestinal obstruction is a common and distressing clinical complication in ovarian cancer. The aim of our study was to assess vomit control in terminal ovarian cancer patients with inoperable gastrointestinal obstruction, using a symptomatic pharmacological treatment with octreotide which obviates the need for nasogastric tube placement. We studied 13 patients, all of whom had advanced ovarian cancer FIGO stage IIIc. Seven patients were treated in the Gynecology Department of S. Raffaele Hospital, at the University of Milan, and 6 were managed in the University of Varese Hospital. Octreotide was administered at doses starting with 0.3 up to 0.6 mg (mean 0.44 mg) a day by subcutaneous bolus or continuous infusion. Octreotide controlled vomiting in all cases to grade 0 on the WHO emesis scale. Complete relief of symptoms was achieved within 3.07 days (range 1-6 days). Vomiting stopped within 2-3 days of starting treatment in most patients. In 8 patients with a nasogastric tube, drainage decreased from 2000 to under 100 ml/day after the start of octreotide treatment. No side effects were reported. All patients died with minimal distress or pain.
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PMID:Octreotide in the management of bowel obstruction in terminal ovarian cancer. 864 13


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