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)

The major difference between cisplatin-based chemotherapy doublets for advanced non-small cell lung cancer (NSCLC) is not in the outcomes of their use--rather, it is in the side effects and toxicities that they cause. The degree to which oncologists involve lung cancer patients in discussions regarding the selection of chemotherapy is unknown. A questionnaire regarding patient concerns about chemotherapy and physician discussions was sent to patients registered in the Alliance for Lung Cancer Advocacy, Support, and Education (ALCASE) database from 2000--2002. About three-quarters of the respondents reported that if they were given the option, they would consider side effects important in choosing a particular regimen--and nausea was the most important side effect that would influence that decision. Female patients were more likely to worry about infection and hair loss resulting from therapy than were men. Further, about two-thirds of patients reported that they had discussed differences in chemotherapy side effects with their physicians, particularly if the physicians were female, although less than half of those patients recalled discussing the selection of a particular regimen based upon its side-effect profile. Different chemotherapy regimens with varied side-effect profiles have been developed, but medical oncologists do not present options for chemotherapy uniformly to their patients based on possible or probable adverse reactions. Better communication between physician and patient about the likelihood of side effects may reduce chemotherapy-related stress for patients.
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PMID:Patient preferences in choosing chemotherapy regimens for advanced non-small cell lung cancer. 1579 47

This phase I/II study was conducted to evaluate the safety and efficacy of tirapazamine in combination with cisplatin and vinorelbine for patients with advanced-stage IIIB/IV chemonaive non-small-cell lung cancer. Seventy patients with a Karnofsky performance status of > or = 60% were included. In the phase I part of the study, 21 patients were treated on day 1 with tirapazamine (escalating doses of 260, 330, or 390 mg/m(2)), cisplatin (75 or 100 mg/m(2)), and vinorelbine (25 or 30 mg/m(2)) for a maximum of 6 cycles every 4 weeks. Vinorelbine was repeated every week. In the phase II part of the study, 49 patients were treated on day 1 with tirapazamine 390 mg/m(2), cisplatin 100 mg/m(2), and vinorelbine 30 mg/m(2). The maximum tolerated dose was not reached. Muscle cramps, vomiting, nausea, tinnitus, neutropenia, and diarrhea were the most frequently reported adverse events in the phase I part of the study. Most of these events were grade 1 or 2. In the phase II part of the study, response rate was 47%, and median survival was 50 weeks. The most frequently reported adverse event was neutropenia. Asthenia, fever, anemia, vomiting, weight decrease, nausea, and muscle cramps were also noted. For patients treated at the maximum dose, dose reductions occurred 14% of tirapazamine cycles and in 4% of cisplatin cycles. The median number of cycles was 3. This regimen has a manageable toxicity profile. Response rate and median survival suggest that this combination might be more active than the cisplatin/vinorelbine combination. This triplet is currently being evaluated in a phase III study.
Clin Lung Cancer 2005 Mar
PMID:Tirapazamine with cisplatin and vinorelbine in patients with advanced non-small-cell lung cancer: a phase I/II study. 1584 80

Despite improvements in conventional treatment, patients with advanced non-small-cell lung cancer (NSCLC) have a poor prognosis, leaving a significant unmet need for novel treatments. One such novel, biologically targeted agent is the orally active epidermal growth factor receptor tyrosine kinase inhibitor gefitinib. This open-label pilot trial investigated the safety, pharmacokinetics, and efficacy of 2 doses of gefitinib (250 and 500 mg per day) combined with docetaxel (75 mg/m2) in patients with locally advanced or metastatic NSCLC as first- and second-line chemotherapy. Eighteen patients were recruited: 6 received gefitinib 250 mg per day plus docetaxel; 12 received gefitinib 500 mg per day plus docetaxel. Combination therapy was feasible with no overlapping toxicities. No patients experienced dose-limiting toxicities (DLTs) at 250 mg per day; 1 patient had 2 DLT events at 500 mg per day (grade 3 rash and diarrhea for >4 days). Adverse events were mild to moderate, including fatigue, mucositis, nausea, anorexia, rash, diarrhea, and fever. Docetaxel did not appear to alter steady-state exposure to gefitinib. The effect of gefitinib on exposure to docetaxel was equivocal; with the exception of 2 patients in the gefitinib 250 mg per day dose group, there appeared to be no trend toward a higher or lower exposure to docetaxel when given in the presence of gefitinib compared with that when given alone. Combination therapy was associated with antitumor activity and responses were seen with gefitinib in 2 of 6 patients at 250 mg per day and 4 of 12 patients at 500 mg per day. This combination is feasible and has an acceptable and predictable safety profile, as well as associated antitumor activity.
Clin Lung Cancer 2005 May
PMID:A pilot trial of gefitinib in combination with docetaxel in patients with locally advanced or metastatic non-small-cell lung cancer. 1594 94

Exisulind is a sulfone derivative of sulindac that induces apoptosis and demonstrates synergy with docetaxel in lung cancer models. This study evaluated the safety, efficacy, and pharmacokinetic interactions of exisulind and docetaxel/carboplatin in patients with metastatic non-small-cell lung cancer (NSCLC). Fifty-seven patients received 218 cycles of docetaxel (75 mg/m2) and carboplatin (area under the curve, 5.0) in combination with exisulind (125-250 mg orally twice daily). Two complete responses and 9 partial responses were observed among the 47 patients assessable for response (overall response rate, 23%). The median duration of response was 5.9 months and median survival was 9.4 months. The 1- and 2-year survival rates are 35% and 14%, respectively. The hematologic toxicities were consistent with those previously reported with docetaxel/carboplatin. The most common nonhematologic toxicities were mild to moderate fatigue, anorexia, nausea, and vomiting. The addition of exisulind to the chemotherapy regimen did not interfere with the metabolism or elimination of docetaxel and vice versa, and docetaxel did not interfere with the pharmacokinetic parameters of exisulind. This trial did not allow direct comparison of patients receiving docetaxel/carboplatin with and without exisulind, but when compared with historical data of docetaxel/carboplatin alone, the addition of exisulind does not appear to enhance antitumor activity, duration of response, or survival. Although preclinical data demonstrate increased apoptosis and prolonged survival for the combination of exisulind and docetaxel, multiple clinical trials do not support further clinical development of this combination regimen in patients with advanced NSCLC.
Clin Lung Cancer 2005 May
PMID:A phase I/II study of exisulind in combination with docetaxel/carboplatin in patients with metastatic non-small-cell lung cancer. 1594 97

Twenty-five patients with histologically proven malignant mesothelioma participated in a trial of imatinib mesylate (Glivec) with a starting dose of 400 mg per day taken orally, up to a maximal dose of 800 mg. No responses were observed in the patient group, while three patients showed prolonged (>6 months) stabilization of disease. The median survival time was 398 days (range 88-840); the median time to progression was 63 days (range 29-275). Side effects of the medication were mild and included edema, nausea, constipation and diarrhea. We conclude that further investigation with monotherapy imatinib in mesothelioma is not warranted.
Lung Cancer 2005 Oct
PMID:Limited efficacy of imatinib mesylate in malignant mesothelioma: a phase II trial. 1595 Oct 53

Though the high incidence of pancreatic metastasis of lung cancer has been reported in autopsy series, symptomatic cases with jaundice due to that is very rare. Dominant histological type with pancreatic metastases is small cell carcinoma and prognosis is poor. Hereby, we report a case initially presenting with gastroenterologic symptoms as jaundice, nausea, vomiting, weight loss and abdominal pain and then diagnosed as primary small cell carcinoma of the lung with metastasis to pancreas. He underwent a palliative surgery due to obstructive jaundice. This presented case is a rare one with its priority of gastroenterologic symptoms rather than pulmonary complaints.
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PMID:A case of a small cell lung carcinoma presenting with jaundice due to pancreatic metastasis. 1661 26

N-methyl-D-aspartate (NMDA) receptor antagonists enhance opioid-induced analgesia. The plasma concentration of ketamine, an NMDA receptor antagonist that enhances epidural morphine-and-bupivacaine-induced analgesia, is not known. We examined 24 patients with lung carcinoma or metastatic lung tumor who underwent video-assisted thoracic surgery in a placebo-controlled, double-blind manner 4 h after emergence from anesthesia. The morphine + ketamine group (n = 8) and morphine + placebo group (n = 8) received 5 mL volume of 2.5 mg morphine and 0.25% bupivacaine and the placebo + ketamine group (n = 8) received 5 mL volume of saline and 0.25% bupivacaine epidurally at the end of skin closure. Four hours after this anesthesia, in the morphine + ketamine and placebo + ketamine groups, ketamine was administered to successively maintain a stable plasma ketamine concentration of 0, 10, 20, 30, 40, and 50 ng/mL by a target-controlled infusion device, and patients assessed the levels of pain at rest, pain on coughing, somnolence (drowsiness), and nausea using a 100-mm visual analog scale (VAS). In the morphine + placebo group, a placebo (saline) was similarly administered instead of ketamine. In the morphine + ketamine group, the VAS scores for pain at rest and pain on coughing significantly decreased on ketamine administration at a plasma concentration of 20 ng/mL or larger compared with the respective baseline VAS scores (P < 0.05 each). In the placebo + ketamine group, the VAS scores for pain at rest and pain on coughing did not significantly change at any plasma concentration of ketamine as compared to the morphine + placebo group. In the morphine + ketamine group, a plasma concentration of ketamine larger than 20 ng/mL did not further reduce VAS scores for pain at rest and pain on coughing. The VAS scores for drowsiness were comparable among the three groups at any plasma concentration of ketamine. Ketamine at a plasma concentration of 20 ng/mL or larger may enhance epidural morphine-and-bupivacaine-induced analgesia. As an adjunct with epidural morphine-and-bupivacaine and considering the safety of small doses, the minimal plasma concentration of ketamine given IV may be approximately 20 ng/mL.
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PMID:Determining the plasma concentration of ketamine that enhances epidural bupivacaine-and-morphine-induced analgesia. 1611 91

This study explores if advanced NSCLC patients with ECOG PS 2 and age<or=65 years can benefit from weekly docetaxel+carboplatin, with acceptable toxicities. Fifty-nine eligible patients with Stage IIIB (effusion) or Stage IV NSCLC were registered. Patients received docetaxel 35mg/m(2) and carboplatin AUC=2 on Days 1, 8, and 15 every 28-day cycle (maximum 8 cycles). Endpoints were 1-year survival, tumor response, PFS, and safety. Among the 59 eligible patients, the 1-year survival was 28% and median survival was 6 months (range: 1-24.3). The median duration of response for CR+PR was 5.4 months (range: 2.3-9.7), 1-year progression-free survival was 14% (median of 3.7 months, range<1-22.8). Patients received a median of 3 cycles (range: 1-9); 14 patients (24%) had toxicity-related reductions. Responses were: 1 CR (2%), 5 PR (10%), 22 SD (45%), and 21 PD (43%). Forty-nine patients were evaluable for response; 10 patients were non-evaluable due to: radiotherapy (1), withdrew consent (3), insurance issues (1), and early toxicity (1 each; dyspnea, weakness, and rash), and other illness (2). Fifty-eight patients were evaluable for safety. The primary Grade 3 or 4 toxicities were neutropenia and fatigue (10% each), nausea (9%), dehydration (7%), and vomiting (5%). A 12% response rate (plus 45% SD) confirms the relatively poor outcome of patients with advanced NSCLC who are PS 2. Toxicities of docetaxel+carboplatin are comparable to other regimens and this combination may provide an alternative for this group of patients. Further studies correlating patient characteristics with response are necessary.
Lung Cancer 2006 Jun
PMID:Results of a Phase II study of weekly docetaxel and carboplatin in Stage IIIB (with effusion) or Stage IV non-small cell lung cancer patients age<or=65 and performance status 2. 1662 Nov 29

The efficacy of salvage regimens for small cell lung cancer remains to be established. We evaluated the efficacy and safety of the paclitaxel and ifosfamide (PI) combination chemotherapy salvage regimen in heavily pretreated small cell lung cancer (SCLC) patients. Thirty-five patients who had received more than two prior chemotherapy regimens were treated with PI chemotherapy. Paclitaxel (175 mg/m(2)) was administered on day 1 and ifosfamide (2500 mg/m(2)) on day 1-2 every 3 weeks. Thirty-three patients were available for treatment response evaluation. Median age was 63 years (range, 40-78) and Eastern Cooperative Oncology Group (ECOG) performance scores of 0/1/2 were 29.4%, 61.8%, and 11.8%, respectively. A median of 2 cycles (range, 1-6) of chemotherapy were administered. The overall response rate (RR) in the intent-to-treat population was 20.0% (95% Confidence Interval (CI), 6.7-33.3%) with 7 partial responses (PR) and no complete response (CR). Patients who responded to previous chemotherapy just before PI showed significantly higher RR than non-responders (RR, 57.1% versus 10.7%, P=.023). After a median follow-up of 8.8 months (range, 1.6-14.7), the median time to progression was 3.3 months (95% CI, 2.3-4.4) and the median overall survival was 7.6 months (95% CI, 6.7-8.5). The most common toxicity observed was mild nausea/vomiting and grade 3/4 adverse events were observed in 4 (11.4%) patients. There were no treatment-related deaths in the study. Our findings suggest that salvage PI chemotherapy is a feasible and well tolerated regimen for previously treated SCLC patients. Further studies are warranted to define the effects of PI chemotherapy on quality of life and survival benefits.
Lung Cancer 2007 Oct
PMID:Combination chemotherapy with paclitaxel and ifosfamide as the third-line regimen in patients with heavily pretreated small cell lung cancer. 1762 73

Even with the standard first-line chemotherapy, advanced non-small cell lung cancer (NSCLC) recurs in most cases. The purpose of this study is to develop a new chemotherapeutic regimen for patients with NSCLC that has relapsed or was refractory to previous chemotherapy. Patients with proven NSCLC refractory or recurrent after previous single-regimen chemotherapy, PS of 0-2, age of 15 years or older, adequate organ functions and measurable lesions were treated with irinotecan at 60 mg/m(2) and cisplatin at 25 mg/m(2) with 1000 ml hydration on day 1. This administration, considered as one cycle, was repeated every week without rest unless encountering defined skip and dose-reduction criteria. The treatment was administered for six cycles over a 49-day period, both median values, to 48 patients, with a response rate of 26%, progression free and median survival times of 3 and 11 months, respectively, and a 1-year survival rate of 46%. The most frequent grade 3 or 4 toxicities were neutropenia, anaemia and nausea, which were manageable. Subset analyses suggested that the response rate was independent of response to the first-line chemotherapy. In conclusion, second-line chemotherapy of weekly irinotecan and cisplatin with minimum hydration seemed effective, with tolerable toxicity, and is potentially useful irrespective of the outcome of previous chemotherapy.
Lung Cancer 2007 Nov
PMID:Phase II study of weekly irinotecan and cisplatin for refractory or recurrent non-small cell lung cancer. 1765 54


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