Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Six patients with recurrent ovarian cancer who had prior chemotherapy were studied for the clinical efficacy of CDDP-ACR treatment. Five out of the 6 had received CDDP a total doses of 1,320, 780, 750, 475, and 340 mg. CDDP-ACR therapy consisted of continuous infusion of CDDP at a daily dose of 10 mg/m2 over 14 days (total CDDP doses; 140 mg/m2) and of intermittent infusion of ACR (aclarubicin) at a dose of 20 mg/body every other day (total ACR doses: 140 mg). There were one CR and five PR and a response rate up to 100% was noted. Toxicity was manifested in slight nausea or vomiting, but there was no nephrotoxicity. However bone marrow was severe. Thrombocytopenia less than 50,000/mcl in 4 pts (67%) and leukopenia less than 1,000 mcl in 3 pts (50%). The mean filterable platinum exposure measured by area under the concentration-time curve (AUC) was as high as 19.7 +/- 6/0 mg.hr/ml. In conclusion the bone marrow toxicity in this regimen was severe, but the therapeutic efficacy was promising. Further studies on the appropriate infusion time and the minimum effective dose of CDDP are needed.
 ...
PMID:[CDDP-ACR treatment in patients with recurrent ovarian cancer with prior chemotherapy containing CDDP--a preliminary study of a 14-day continuous infusion of CDDP with ACR]. 258 9

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.
 ...
PMID:A phase II study of carboplatin and cyclophosphamide in advanced ovarian carcinoma. 845 65

The topoisomerase I inhibitor topotecan has shown antitumour activity against a variety of tumour types in vitro and in vivo. Topotecan in combination with drugs that induce DNA damage generally results in synergistic killing of tumour cells in vitro. As the activity of topotecan is related to exposure time, the drug is administered by intravenous infusion either continuously or once daily over a 30-minute period for several consecutive days. A 30-minute infusion of topotecan 1.5 mg/m2 on 5 consecutive days every 3 weeks produced response rates of up to approximately 20% in patients with advanced ovarian cancer who had failed to respond to platinum-based regimens or relapsed after initial response to such regimens. No significant differences in efficacy were apparent between topotecan and paclitaxel in a phase III study in patients with recurrent ovarian cancer, although a trend in favour of topotecan was evident for all major efficacy parameters. Non-cumulative myelosuppression, including neutropenia, thrombocytopenia and anaemia, is the dose-limiting toxicity associated with topotecan. Myelo-suppression was significantly more common with topotecan than with paclitaxel in a single comparative study. Non-haematological adverse events in topotecan recipients are generally mild and include alopecia, nausea, vomiting, and other gastrointestinal problems. Thus, topotecan has modest efficacy in the treatment of recurrent advanced ovarian cancer, with clinical activity similar to that of paclitaxel in a large randomised phase III study in this setting. Combinations of paclitaxel and a platinum compound are being used increasingly for first-line therapy, although relapse rates remain significant. Topotecan is therefore a suitable second-line option, providing antitumour response for some patients whose disease has relapsed after, or is refractory to, platinum-based therapy. Its wider potential when used either alone or in combination regimens should become clearer from ongoing studies.
 ...
PMID:Topotecan. A review of its potential in advanced ovarian cancer. 980 12

A Phase I study of paclitaxel and doxorubicin administered as concurrent 96-h continuous i.v. infusion was performed to determine the maximum tolerated dose (MTD), principal toxicities, and pharmacokinetics of this combination in women with relapsed epithelial ovarian cancer. The paclitaxel dose was fixed at 100 mg/m2 (25 mg/m2/day for 4 days). The dose of doxorubicin was escalated from 30 mg/m2 (7.5 mg/m2/day for 4 days) in increments of 10 mg/m2 until dose-limiting toxicity was observed. All patients received granulocyte colony-stimulating factor 5 microg/kg/day prophylactically. Apparent steady-state plasma levels of both drugs were determined in the final cohort of patients treated at the MTD. A total of 17 patients received 52 cycles of therapy. The median age was 58 years, and all patients had previously received one to five different regimens (median, 2) of chemotherapy, including both platinum and paclitaxel. The treatment was tolerated well, with grade 1-2 nausea being the most frequent side effect (73% of cycles). Anemia, neutropenia, thrombocytopenia, and mucositis became dose limiting at the fourth dose level, defining the MTD of doxorubicin in this regimen as 50 mg/m2. There were four partial responses and one complete response in 15 evaluable patients. Apparent steady-state plasma concentrations (mean +/- SD) of paclitaxel and doxorubicin in the three patients treated at the MTD were 33.9 +/- 12.5 nM and 15.7 +/- 1.3 nM, respectively. Paclitaxel and doxorubicin by continuous infusion is a well-tolerated and active chemotherapy regimen for recurrent ovarian cancer.
 ...
PMID:A Phase I study of continuous infusion doxorubicin and paclitaxel chemotherapy with granulocyte colony-stimulating factor for relapsed epithelial ovarian cancer. 1038 12

We evaluated the feasibility of high-dose CEP (cyclophosphamide 750 mg/m2, epirubicin 90 mg/m2, cis-platinum 70 mg/m2) therapy, with granulocyte colony-stimulating factor support every 21 days, in 18 patients with advanced and recurrent ovarian cancer. Ten patients (56%) received 6 cycles of this regimen as planned. Toxicities more than grade 3/4 on' the WHO scale of neutropenia and thrombocytopenia were observed in all cases. Nausea, vomiting, mucositis, malaise, alopecia, hepatotoxicity, and fever were common adverse effects. The average relative dose intensity of cyclophosphamide, epirubicin, cis-platinum was 0.77, 0.77, 0.79 respectively, and each RDI decreased in the last two cycles. These data suggest that this regimen could be performed safely with careful consideration on hepatotoxicity and thrombocytopenia.
 ...
PMID:[A pilot trial of high dose CEP (cyclophosphamide, epirubicin, cis-platinum) therapy in patients with advanced and recurrent ovarian cancer]. 1079 Oct 1

Gemcitabine and oxaliplatin have shown single-agent activity in relapsed ovarian cancer. This combination was used to determine response rates, time-to-event efficacy measures, and toxicity in patients with recurrent ovarian cancer. Patients with prior platinum-based chemotherapy who had measurable lesions and/or elevated CA-125 levels were identified as group A (platinum-refractory/platinum-resistant patients) and group B (platinum-sensitive patients). All patients received gemcitabine 1000 mg/m(2) on days 1 and 8 and oxaliplatin 130 mg/m(2) on day 8 every 21 days for up to eight cycles. Seventy-five patients (21 in group A and 54 in group B), with a median age of 58 years (range, 37-78), were enrolled. A median of six cycles (range, 1-8) was administered. By intent-to-treat analysis, 15 patients with measurable disease achieved partial response for an overall best response rate of 20.0% (9.5% in group A and 24.1% in group B). CA-125 response was observed in 48.4% patients (30.0% in group A and 57.1% in group B). Median time to progressive disease was 7.1 months (95% CI, 5.6-9.0 months) with 5.0 months in group A and 8.3 months in group B. Median overall survival was 17.8 months (95% CI, 12.9-21.3 months) with 9.2 months for group A and 20.0 months for group B. Major grade 3/4 toxicities were neutropenia (61.3%), leukopenia (24.0%), nausea (16.0%), and vomiting (22.7%). We conclude that the combination of oxaliplatin and gemcitabine is active in patients with recurrent ovarian cancer, but the regimen is unsatisfactory for further study due to modest response and relatively high toxicity.
 ...
PMID:Phase II study of gemcitabine and oxaliplatin in patients with recurrent ovarian cancer: an Australian and New Zealand Gynaecological Oncology Group study. 1736 13

The purpose of this study was to estimate the response rate of 26-h continuous infusion cyclosporine A (CSA) combined with carboplatin (CBDCA) and subcutaneous alpha-interferon (IFN), in recurrent ovarian cancer (OC), and to measure their effects on CBDCA pharmacokinetics. OC patients relapsing following platinum-based chemotherapy received CBDCA area under the curve (AUC 3) with CSA and IFN, every 3 weeks. The pharmacokinetics of CSA and CBDCA were determined in a subset of patients. Thirty patients received 84 courses of therapy. Three partial responses were observed. Nine patients were stable for >4 months. Toxicity was similar to that observed in our previously reported phase I study and consisted of myelosuppression, nausea, vomiting, and headache. The mean end of infusion CSA level (high-performance liquid chromatographic assay [HPLC]) was 1109 +/- 291 microg/mL (mean +/- SD). CBDCA pharmacokinetics revealed a measured AUC of 3.61 versus a targeted AUC of 3, suggesting a possible effect of IFN on CBDCA levels versus errors in the estimation of CBDCA clearance using measured creatinine clearance. Steady-state levels of >1 microg/mL CSA (HPLC assay) are achievable in vivo. Insufficient clinical resistance reversal was observed in this study to warrant further investigation of this combination.
 ...
PMID:Phase II trial of carboplatin and infusional cyclosporine with alpha-interferon in recurrent ovarian cancer: a California Cancer Consortium Trial. 1736 15

The objective of this study was to determine the objective response rate in patients with platinum-sensitive and platinum-resistant recurrent ovarian cancer to treatment with trabectedin (Yondelis) administered as a 3-h infusion weekly for 3 weeks of a 4-week cycle. We carried out a multicentre Phase II trial of trabectedin in patients with advanced recurrent ovarian cancer. Trabectedin (0.58 mg m(-2)) was administered via a central line, after premedication with dexamethasone, to 147 patients as a 3-h infusion weekly for 3 weeks followed by 1-week rest. Major eligibility criteria included measurable relapsed advanced ovarian cancer and not more than two prior platinum-containing regimens. Patients were stratified according to the treatment-free interval (TFI) between having either platinum-sensitive (>/=6 months TFI) or platinum-resistant disease (<6 months TFI)/platinum-refractory disease (progression during first line therapy). In the platinum-sensitive cohort, 62 evaluable patients with measurable disease had an overall response rate (ORR) of 29.0% (95% CI: 18.2-41.9%) and median progression-free survival (PFS) was 5.1 months (95% CI: 2.8-6.2). Four patients with measurable disease per Response Evaluation Criteria in Solid Tumours (RECIST) criteria had no follow-up scans at the end of treatment. In the platinum-resistant/refractory cohort, 79 patients were evaluable with an ORR of 6.3% (95% CI: 2.1-14.2%). Median PFS was 2.0 months (95% CI: 1.7-3.5 months). Two patients with measurable disease per RECIST criteria had no follow-up scans at the end of treatment. The most frequent (>/=2% of patients) drug-related treatment-emergent grade 3/4 adverse events were reversible liver alanine transferase elevation (10%), neutropaenia (8%), nausea, vomiting, and fatigue (5% each). Trabectedin is an active treatment, with documented responses in patients with platinum sensitive advanced relapsed ovarian cancer, and has a manageable toxicity profile.
 ...
PMID:A Phase II study of trabectedin single agent in patients with recurrent ovarian cancer previously treated with platinum-based regimens. 1800 May 4

Both oxaliplatin (OXA) and gemcitabine (GEM) have shown single agent activity in patients with recurrent ovarian cancer. Response rates to second-line therapies remain low and there is a need to develop more effective regimens. In view of the synergistic effect of using GEM followed by OXA, we studied these agents in elderly patients with recurrent ovarian cancer refractory or resistant to first-line chemotherapy using platinum with or without paclitaxel. The aim of the study was to evaluate the efficacy and toxicity of combination GEM 1000 mg/m(2) Day 1 i.v. and OXA 100 mg/m(2) in 2h infusion Day 2; treatment was repeated every 2 weeks for 6 courses or until progression of disease or intolerable toxicity. The study was monoinstitutional and started in November 2002. 21 patients, median age 68.6 years (range 65-82) have been treated. Median Performance Status was 0-1, all had at least 1 prior platinum based chemotherapy and 11 had received also a taxane. Patients received a median of 6 cycles of treatment (range 4-11). There were 2 patient (9%) with complete response, 3 patients (14%) achieved a partial response. Low profile toxicity (grade 1-2, WHO criteria) was observed: nausea/vomiting 52%, thrombocytopenia 13%, neuropathy 28%. The GEMOX combination is well tolerated and even in this small group of patients, encouraging responses were documented.
 ...
PMID:Gemcitabine combined with oxaliplatin (GEMOX) as salvage treatment in elderly patients with advanced ovarian cancer refractory or resistant to platinum: a single institution experience. 1807 58

In this review, we summarized nine major clinical advances in gynecology which occurred in 2009. For cervical cancer, the role of human papillomavirus (HPV) test as a screening test, the efficacy of HPV vaccine for middle-aged women, randomized controlled trial (RCT) regarding concurrent chemoradiation using gemcitabine plus cisplatin, and the efficacy of pazopanib for metastatic or recurrent disease were chosen. For endometrial cancer, the necessity of systematic pelvic lymphadenectomy in early endometrial cancer was reviewed. For ovarian cancer, the timing of treatment initiation for recurrent ovarian cancer, dose-dense chemotherapy as postoperative adjuvant treatment, the best chemotherapy regimen for platinum-sensitive recurrent ovarian cancer, and the efficacy of target agents were selected. In addition, the results of RCT testing the benefit of ginger in preventing post-chemotherapy nausea were examined.
 ...
PMID:Major clinical research advances in gynecologic cancer 2009. 2004 Oct 96


1 2 Next >>