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

Many attempts have been made to achieve good selectivity to targeted tumor cells by preparing specialized carrier agents that are therapeutically profitable for anticancer therapy. Among these, liposomes are the most studied colloidal particles thus far applied in medicine and in particular in antitumor therapy. Although they were first described in the 1960s, only at the beginning of 1990s did the first therapeutic liposomes appear on the market. The first-generation liposomes (conventional liposomes) comprised a liposome-containing amphotericin B, Ambisome (Nexstar, Boulder, CO, USA), used as an antifungal drug, and Myocet (Elan Pharma Int, Princeton, NJ, USA), a doxorubicin-containing liposome, used in clinical trials to treat metastatic breast cancer. The second-generation liposomes ("pure lipid approach") were long-circulating liposomes, such as Daunoxome, a daunorubicin-containing liposome approved in the US and Europe to treat AIDS-related Kaposi's sarcoma. The third-generation liposomes were surface-modified liposomes with gangliosides or sialic acid, which can evade the immune system responsible for removing liposomes from circulation. The fourth-generation liposomes, pegylated liposomal doxorubicin, were called "stealth liposomes" because of their ability to evade interception by the immune system, in the same way as the stealth bomber was able to evade radar. Actually, the only stealth liposome on the market is Caelyx/Doxil (Schering-Plough, Madison NJ, USA), used to cure AIDS-related Kaposi's sarcoma, resistant ovarian cancer and metastatic breast cancer. Pegylated liposomal doxorubicin is characterized by a very long-circulation half-life, favorable pharmacokinetic behavior and specific accumulation in tumor tissues. These features account for the much lower toxicity shown by Caelyx in comparison to free doxorubicin, in terms of cardiotoxicity, vesicant effects, nausea, vomiting and alopecia. Pegylated liposomal doxorubicin also appeared to be less myelotoxic than doxorubicin. Typical forms of toxicity associated to it are acute infusion reaction, mucositis and palmar plantar erythrodysesthesia, which occur especially at high doses or short dosing intervals. Active and cell targeted liposomes can be obtained by attaching some antigen-directed monoclonal antibodies (Moab or Moab fragments) or small proteins and molecules (folate, epidermal growth factor, transferrin) to the distal end of polyethylene glycol in pegylated liposomal doxorubicin. The most promising therapeutic application of liposomes is as non-viral vector agents in gene therapy, characterized by the use of cationic phospholipids complexed with the negatively charged DNA plasmid. The use of liposome formulations in local-regional anticancer therapy is also discussed. Finally, pegylated liposomal doxorubicin containing radionuclides are used in clinical trials as tumor-imaging agents or in positron emission tomography.
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PMID:From conventional to stealth liposomes: a new frontier in cancer chemotherapy. 1290 76

Oral capecitabine is a highly active, well-tolerated and convenient treatment for breast and colorectal cancer. This trial assessed the efficacy and safety of single-agent capecitabine in patients with previously treated ovarian cancer. A total of 29 patients with platinum-pretreated relapsed ovarian cancer were enrolled in this prospective, open-label, single-centre, phase II study. Patients received oral capecitabine 1250 mg m(-2) twice daily on days 1-14 of a 21-day cycle. Tumour response was evaluated using serum CA125. Out of 29 enrolled patients, 28 were evaluable, and a response was observed in eight patients (29%, 95% confidence interval (CI), 13-49%). Median progression-free and overall survivals were 3.7 (95% CI, 2.8-4.6) and 8.0 (95% CI, 4.1-11.8) months, respectively. After 6 months of treatment, 28% (95% CI, 13-48%) of patients remained progression-free and 62% (95% CI, 42-79%) were still alive. The most common clinical adverse events were hand-foot syndrome (HFS), nausea and diarrhoea. Grade 3 HFS occurred in 14% of patients, grade 3 vomiting in 10%. Efficacy and safety of capecitabine compare favourably with other monotherapies in platinum-refractory epithelial ovarian cancer. The convenience and improved safety profile of capecitabine compared with intravenous. regimens make it an ideal agent for administration in the outpatient setting.
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PMID:A phase II trial of capecitabine (Xeloda) in recurrent ovarian cancer. 1461 90

An estimated 2,500 women were diagnosed with and 1,500 died from ovarian cancer in Canada in 2002. Up to 42% of patients in the palliative phase develop a malignant bowel obstruction. Options for management include medical therapy, surgery, and/or a percutaneous endoscopic gastrostomy (PEG) tube. The objective of this quality improvement study was to: 1) examine if successful palliation was achieved using a PEG tube, and 2) identify opportunities to improve the quality of nursing care provided. A retrospective review of 24 patient records revealed that 75% did not have nausea/vomiting by time of discharge; 92% resumed a clear fluid diet; 83% were discharged from the acute care setting; and 70% did not require re-admission. A PEG tube may effectively palliate women with non-operable bowel obstruction in advanced/recurrent cancer of the ovary. Opportunities for improving care are presented.
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PMID:Managing bowel obstruction in ovarian cancer using a percutaneous endoscopic gastrostomy (PEG) tube. 1469 64

Adverse effects of first-line combination chemotherapy performed with paclitaxel (PTX) and carboplatin (CBDCA) (TJ regimen) on 15 ovarian cancer patients who had had no prior chemotherapy with cisplatin (CDDP) were reviewed retrospectively according to National Cancer Institute common toxicity criteria. The M group (M) consisted of 7 patients treated with a total of 45 courses of the M-TJ regimen. Every 3-4 weeks, PTX was administered as a 3-hour infusion at the average dose level of 175 mg/m2/course on day 1 and CBDCA (targeted AUC = 6) was also administered on day 1. The W group (W) consisted of 10 patients who received a total of 49 courses of the W-TJ regimen. They were treated with PTX (80 mg/m2, 1 h, average dose level = 203 mg/m2/course) on day 1, 8 and 15, and with CBDCA (targeted AUC = 5) on day 1 every 4 weeks. Adverse events with grade 3 or above hematologic toxicity were oligochromemia (M: 24.4%, W: 22.4%), leukopenia (M: 55.6%, W: 40.8%), neutropenia (M: 84.4%, W: 61.2%) and thrombocytopenia (M: 17.8%, W: 8.2%). Grade 3 or above nonhematologic toxicity was not found in the W group, and anorexia (2.2%), nausea (2.2%), diarrhea (2.2%) and arrhythmia (2.2%) were developed only in the M group patients. Toxicity grades for neutropenia, arthralgia, myalgia and neuropathy were significantly lower in the W group. Based on the collected data, the W-TJ regimen is considered to be more effective than the M-TJ regimen for reducing the grade and occurrence of adverse events in ovarian cancer patients.
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PMID:[Paclitaxel plus carboplatin in ovarian cancer-comparison of adverse effects between monthly and weekly administration]. 1511 99

The glucocorticoid dexamethasone is frequently used as a co-treatment in cytotoxic cancer therapy, e.g. to prevent nausea, to protect normal tissue or for other reasons. While the potent pro-apoptotic properties and supportive effects of glucocorticoids to tumour therapy in lymphoid cells are well studied, the impact on the cytotoxic treatment of ovarian carcinoma is unknown. We tested apoptosis-induction, viability, tumour growth and protein expression using established cell lines, primary cell lines freshly isolated from patient material and a xenograft on nude mice. We found a general induction of resistance toward cytotoxic therapy by DEX-co-treatment in most of the examined ovarian cancer cells treated in vitro, ex vivo or in vivo. Resistance occurred independently of cell density and was found at peak plasma levels of dexamethasone and below. Mechanistically, the dexamethasone-induced expression of survival genes may be involved in the resistance. These data show that glucocorticoid-induced resistance is common in ovarian carcinomas implicating that the use of glucocorticoids may be harmful for cancer patients.
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PMID:Glucocorticoid-mediated inhibition of chemotherapy in ovarian carcinomas. 1639 12

We carried out a phase II nonrandomized study to examine the level of activity of oxaliplatin, pegylated liposomal doxorubicin, and cyclophosphamide in a patient population with relapsed ovarian cancer pretreated with platinum derivatives and paclitaxel. Patients received oxaliplatin (85 mg/m2), pegylated liposomal doxorubicin (30 mg/m2), and cyclophosphamide (750 mg/m2). A total of 49 patients (39 assessable for toxicity and response) were enrolled in this trial. Neutropenia grade 3 was observed in six patients (15%) and anemia grade 3 in one patient (0.2%). Fatigue grade 1-2 occurred in 26 patients (66%), nausea/vomiting grade 1 in 23 patients (58%), and alopecia grade 1-2 in 19 patients (48%). Twenty-one (53%) patients experienced grade 1-2 peripheral neuropathy. The overall response rate was 46% (95% CI 23.6-68.7). Median progression-free survival was 28 weeks (range 12-52 weeks) and median survival was 45 weeks (range 26-136+ weeks). The mean duration of response was 34 weeks (range 16-52 weeks). In platinum-resistant and -refractory ovarian cancer patients, the overall response rate was 37% (CI 95% 14.4-60.8) with a progression-free survival of 28 weeks (range 12-52 weeks) and a median survival of 42 weeks (range 28-84 weeks). This combination chemotherapy is generally well tolerated and is an active second-line regimen against ovarian cancer.
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PMID:A phase II study of pegylated liposomal doxorubicin oxaliplatin and cyclophosphamide as second-line treatment in relapsed ovarian carcinoma. 1651 72

This study used electronic diaries to examine patterns of mood and physical symptoms within and across days in two independent samples of cancer patients. Twenty-three breast cancer survivors (post-treatment) and 33 ovarian cancer survivors (on chemotherapy) recorded mood and physical symptoms 4 times daily for 7 consecutive days. A series of repeated-measures multilevel models using SAS Proc Mixed were calculated to estimate the degree to which physical symptoms (e.g., pain, fatigue, and nausea) were associated with participants' moods. Across days, mood vectors with a pleasantness component (i.e., happy-sad and calm-anxious) and mood vectors with an arousal component (i.e., active-passive and peppy-tired) were significantly associated with physical symptom severity. Specifically, breast cancer survivors with greater fatigue and pain reported more negative moods (eta2 < or = 0.33). Ovarian cancer survivors with greater fatigue (eta2 < or = 0.35), pain (eta2 < or = 0.04), and nausea (eta2 < or = 0.04) also reported more negative moods. Diurnal analyses showed that happy-sad (eta2 < or = 0.16), active-passive (eta2 < or = 0.27), and peppy-tired moods (eta2 < or = 0.33) were significantly negatively associated with fatigue at each of the four daily assessment times in both samples. Although correlational, our findings are consistent with previous studies suggesting that variations in both pleasant and aroused mood covary with changes in real-time physical symptom reports.
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PMID:Mood states associated with transitory physical symptoms among breast and ovarian cancer survivors. 1670 84

This study assesses the feasibility and implementation of respiratory-gated whole-abdominal intensity-modulated radiation therapy (RG-WAIMRT). Three patients were treated with RG-WAIMRT. The planning target volume (PTV1) included the entire peritoneal cavity and a pelvic boost field was created (PTV2). The dose prescribed was 30 Gy to PTV1 and 14.4 Gy to PTV2. For comparison, a conventional three-dimensional (3D) plan was generated for each patient. In the WAIMRT plan, an average of 90% of PTV1 received 30 Gy compared to 70% for the conventional 3D plan. The percent volume receiving 30 Gy (V(30)) for liver averaged 54% (WAIMRT) vs 43% (3D). The percent volume receiving 20 Gy (V(20)) for kidneys averaged 19% vs 0%, and the mean V(20) for bone marrow was 74% vs 83%, respectively. Major acute toxicities were anemia (grade 2: 1/3), leukopenia (grade 3: 2/3 patients), and thrombocytopenia (grade 2: 1/3 patients, grade 3: 1/3 patients). One patient could not complete the whole-abdomen field after 19.5 Gy because of persistent nausea. No major subacute toxicity has been reported. WAIMRT demonstrated superior target coverage and reduced dose to bone marrow, with a slightly increased dose to liver and kidneys. WAIMRT is a novel and feasible technique for ovarian cancer treatment.
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PMID:Four-dimensional computed tomography-based respiratory-gated whole-abdominal intensity-modulated radiation therapy for ovarian cancer: a feasibility study. 1729 Dec 32

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.
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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

This phase I study sought to determine the toxicity profile, pharmacokinetics, and antitumor activity of giving carboplatin every 3 weeks and paclitaxel weekly in patients with relapsed ovarian cancer. Eligible patients with relapsed epithelial ovarian cancer and prior treatment with platinum- and paclitaxel-based therapy were treated with an escalating regimen of carboplatin (day 1) at an area under the curve (AUC) of 4-6 and 1-h infusions of paclitaxel (days 1, 8, and 15) at 50-80 mg/m(2) cycled at 3-week intervals. Pharmacokinetic studies were performed on the first day of cycles 1 and 2. All patients had a platinum-free interval of greater than 6 months from the most recent platinum treatment. A total of 77 cycles were administered to 16 patients, with a similar median number of cycles per patient at each dose level varying from 4.6 to 5.3. Febrile neutropenia and grade 4 thrombocytopenia were the dose-limiting toxicities at dose levels 3 and 4 after the third cycle, with no mucositis, nausea, vomiting, or peripheral neuropathy observed greater than grade 2. The maximum tolerated dose of carboplatin was an AUC of 5 and 80 mg/m(2) for paclitaxel. Pharmacokinetic analysis showed a marginal statistical difference with regard to reduced systemic paclitaxel concentration after cycle 2 compared with cycle 1 (P= 0.06). Of nine patients evaluable for a radiographic response, the response rate was 66.6% with a complete response of 33.3%. All five patients with nonmeasurable disease achieved a biochemical response. The combination of carboplatin given every 3 weeks at an AUC of 5 and 1-h weekly paclitaxel at 80 mg/m(2) is a feasible and reasonably well-tolerated regimen and may have significant antitumor activity in relapsed ovarian cancer patients.
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PMID:A phase I study evaluating the safety and pharmacokinetics of weekly paclitaxel and carboplatin in relapsed ovarian cancer. 1736 16


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