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)

An early phase II cooperative study of Gemcitabine Hydrochloride (abbreviated to "gemcitabine" herewith) was conducted in patients with a variety of solid tumors (i.e., lung cancer, gastric cancer, pancreatic cancer, colon/rectum cancer, cervical cancer, ovarian cancer and breast cancer) at 56 institutions. The aim of the first step (Step I) was to investigate the feasibility of gemcitabine in a variety of different solid tumors, including lung cancer regarding efficacy and safety. The aim of the second step (Step II) was as a result of step I (Responses were observed) to continue to investigate the efficacy and safety of gemcitabine in chemonaive patients with non-small cell lung cancer. As a Step I study, gemcitabine was administered once weekly at a dose of 800 mg/m2 for a consecutive 3-week period followed by a week of rest, in multiple courses. Among the 29 eligible patients with lung cancer, partial response (PR) was achieved in 3 patients (25.0%, 95% confidence interval: 5.5-57.2%) out of 12 chemonaive patients. Adverse reactions (grade 3 or higher) seen in 29 patients with lung cancer were neutropenia (27.6%), leukopenia (13.8%), decreased hemoglobin (13.8%), thrombocytopenia (10.3%), malaise (6.9%), anorexia (3.4%), nausea/vomiting (3.4%), diarrhea (3.4%), dyspnea (3.4%) and interstitial pneumonia (3.4%). In other types of solid tumors, PR was achieved in 2 (8.7%) out of 23 eligible patients with cervical cancer and in 1 (5.3%) of 19 eligible patients with ovarian cancer, while the use of analgesics became unnecessary in 1 patient with pancreatic cancer. Incidence as well as severity of main adverse reactions in these patients were comparable to those seen in patients with lung cancer. A Step II study, in which gemcitabine was administered once weekly at a dose of 1,000 mg/m2 to chemonaive patients with non-small cell lung cancer, was conducted, referring to the results of Step I and clinical studies conducted overseas. The results of the Step II study demonstrated PR in 5 (14.3%, 95% confidence interval: 4.8 - 30.3%) out of 35 eligible patients with non-small cell lung cancer and that the main adverse reactions were comparable to those seen in the Step I study, posing no tolerability problems in particular.
 ...
PMID:[An early phase II study of gemcitabine hydrochloride (LY 188011). Gemcitabine Cooperative Study Group for Early Phase II]. 893 92

Fifteen patients with stage II, IIIA, and IIIB non-small cell lung cancer (NSCLC) received subcutaneous (s.c.) recombinant, glycosylated, human interferon-beta 1a (Rebif; rHuIFN-beta 1a) on each day of conventionally fractionated radiation therapy (RT) given in 2.0 Gy fractions to 60 Gy in 6 weeks. The rHuIFN-beta 1a was generated in CHO cells by recombinant DNA technology and is identical to natural IFN-beta produced by fibroblasts in primary sequence and glycosylation. Cohorts of three patients each were treated with escalating doses of rHuIFN-beta 1a: 1.5, 3, 6, 12, and 24 MIU/m2 per treatment day. Acute toxicity was assessed according to modified WHO criteria; late toxicity was graded using RTOG late toxicity criteria. The maximum tolerated dose (MTD) of rHuIFN-beta 1a was defined as the dose level immediately below that in which dose-limiting toxicity occurred in > or = two of six patients. Immunomodulatory effects and antigenicity of rHuIFN-beta 1a were assessed by 2-5A synthetase, beta 2-microglobulin, and neopterin levels and by measurement of anti-rHuIFN-beta antibodies, respectively. Fourteen of fifteen patients experienced grades 1-3 acute (early) toxicity (< or = 90 days), which was primarily gastrointestinal: dysphagia/esophagitis (14/15), nausea/vomiting (12/15), anorexia (7/15), and liver transaminasemia (6/15). One of three patients treated with 24 MIU/m2 per treatment day (total rHuIFN-beta 1a dose 672 MIU) died of complications secondary to pneumonia, sepsis, adult respiratory distress syndrome (ARDS), and radiation pneumonitis. Twelve patients were evaluable for late toxicity (> 90 days). Maximum toxicity was grade 0 in five patients, grade 1 in four patients, and grade 5 in one patient (radiation pneumonitis). Clinical responses from the combination were 1/15 CR, 6/15 PR, 6/15 stable disease, and 1/15 progressive disease. The MTD of rHuIFN-beta 1a has been estimated at 12 MIU/m2 per treatment day when given daily during conventional RT to 60 Gy in 6 weeks. Biologic response by rHuIFN-beta 1a alone was reflected by significant and dose-related increases in 2-5A synthetase, beta 2-microglobulin, and neopterin. Radiation therapy alone had no effect on these immune response parameters and did not diminish their augmentation by rHuIFN-beta 1a. There was no association of biologic modulation with clinical response or survival.
 ...
PMID:Recombinant human interferon-beta (rHuIFN-beta) and radiation therapy for inoperable non-small cell lung cancer. 893 64

We performed a clinical phase II trial of the combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and cisplatin in patients with locally advanced (stage IIIB) or metastatic non-small cell lung cancer (NSCLC), using a 3-hour infusion of paclitaxel followed by a 1-hour infusion of cisplatin. Treatment was repeated every 21 days, for a maximum of six cycles. The patients received paclitaxel 175 mg/m2 followed by cisplatin 75 mg/m2. At present, 52 chemotherapy-naive patients with stage IIIB (17.3%) or stage IV (82.7%) NSCLC have been entered into this ongoing trial. Ten (19%) of the patients are women and 42 (81%) are men. With 197 courses of chemotherapy given, all 52 patients are evaluable for toxicity. Hematologic toxicities were moderate: World Health Organization (WHO) grade 3 or 4 neutropenia occurred in 38.7% of the cycles (47.7% of patients), and WHO grade 3 or 4 thrombocytopenia was observed in 1.5% of cycles (3.8% of patients). Other toxicities consisted mainly of WHO grade 2 or 3 alopecia and nausea/vomiting. World Health Organization grade 1 or 2 polyneuropathy occurred in 30.4% and grade 3 or 4 only in 1% of all courses. Of 40 patients evaluable for response, a complete remission was noted in one patient, a partial remission occurred in 13 patients (32.5%), stable disease was seen in 14 patients (35%), and disease progressed in 12 patients (30%). These results suggest that the combination of paclitaxel and cisplatin is active and tolerable in the treatment of NSCLC. The efficacy of the combination seems high in this poor-prognosis population.
 ...
PMID:Paclitaxel and cisplatin in patients with non-small cell lung cancer: results of a phase II trial. 894 3

In studies conducted by the Eastern Cooperative Oncology Group, treatment with either paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) or carboplatin was associated with an improvement in 1-year survival in patients with stage IV non-small cell lung cancer (NSCLC). Based on these findings, a phase II trial of carboplatin plus paclitaxel was conducted in patients with advanced NSCLC to determine the activity and toxicity of this regimen. Eligibility requirements included stage IIIB or IV histologically confirmed NSCLC, Eastern Cooperative Oncology Group performance status of 0 to 2, no prior chemotherapy, and adequate hematologic, renal, hepatic, and cardiac functions. Paclitaxel was administered intravenously over 24 hours at a dose of 135 mg/m2 (28 patients) or 175 mg/m2 (23 patients), followed by a 1-hour infusion of carboplatin on day 2. Carboplatin was administered at a dose of 300 mg/m2 (16 patients) or, using the Calvert formula, a dose calculated to achieve an area under the concentration-time curve of 6 mg/mL x min (35 patients). Treatment was repeated every 28 days for a total of six cycles. Among the 51 eligible patients, 34 were men and 17 were women; their median age was 60 years and their median Eastern Cooperative Oncology Group performance status was 1. Six patients had stage IIIB and 45 had stage IV disease. Grade 3 or 4 granulocytopenia and thrombocytopenia were observed in 47% and 3% of treatment cycles, respectively. The most common nonhematologic toxicities noted included nausea and emesis, neuropathy, and arthralgia and myalgia. There were no complete responses and 14 partial responses, for an overall response rate of 27% (95% confidence interval, 17% to 41%). Median survival was 38 weeks and the survival rate at 1 year was 32%. Paclitaxel plus carboplatin, as given in this study, was found to be a moderately active regimen in patients with advanced NSCLC. This regimen warrants comparison with existing cisplatin-based regimens in a prospective randomized trial.
 ...
PMID:Paclitaxel plus carboplatin in the treatment of patients with advanced lung cancer: a Vanderbilt University Cancer Center phase II trial (LUN-46). 900 20

Few cytotoxic agents tested in adequate phase II trials involving patients with non-small cell lung cancer have produced single-agent response rates greater than 15%. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is one of them, with reported response rates ranging from 21% to 36%. Platinum-based regimens have been key to the development of the most effective combination therapies for NSCLC. We are currently investigating the efficacy and toxicity of combining paclitaxel (175 mg/m2) given by 3-hour infusion, followed by cisplatin (75 mg/m2) via 1-hour infusion, on a 21-day schedule for the treatment of 75 chemotherapy-naive patients with stage IIIB (17.3%) or stage IV (82.6%) non-small cell lung cancer. Patient characteristics include a median age of 58 years (age range, 28 to 75 years) and a median Eastern Cooperative Oncology Group performance status of 2; 19 patients (25.3%) are women and 56 (74.7%) are men. All patients received standard prophylactic premedication as well as adequate hydration. To date, 75 subjects and 328 courses are evaluable for toxicity. Hematologic toxicities have been moderate; grade 3 or 4 neutropenia occurred in 37% of cycles (50% of patients), and grade 3 or 4 thrombocytopenia was observed in only 2% of cycles (2% of patients). Other notable toxicities were World Health Organization grade 2 or 3 alopecia and nausea/vomiting. Grade 1 or 2 peripheral neuropathy occurred in 26% and grade 3 or 4 in only 1% of all courses. Of 67 patients evaluable for response, complete remission was noted in three (5%) patients, partial remission in 25 (37%) patients, stable disease in 22 (33%) patients, and progressive disease in 17 (25%) patients. These results suggest that combination paclitaxel/cisplatin is active and well tolerated in the treatment of non-small cell lung cancer.
 ...
PMID:Phase II study of paclitaxel and cisplatin in patients with non-small cell lung cancer. 900 21

To determine the activity and toxicity of gemcitabine (2',2'-difluorodeoxycytidine), three phase II single-agent studies have been conducted in patients with non-small cell lung cancer in Japan. In an early phase II study, 17 previously treated and 47 untreated patients were treated with gemcitabine. Gemcitabine was given intravenously at a dose of 800 mg/m2 or 1,000 mg/m2 once a week for 3 weeks followed by a week of rest, repeating every 4 weeks. Although none of the patients with prior therapy responded, eight (17%) of 47 previously untreated patients showed a partial response. Toxicities of grade 3 or greater included leukopenia (12.5%), thrombocytopenia (6.3%), and anemia (15.6%). We entered 73 patients (group A) and 67 patients (group B) into two late phase II studies. All patients had no previous chemotherapy and had measurable disease. Gemcitabine was administered at a starting dose of 1,000 mg/m2/wk for 3 weeks followed by a week of rest. The dose was escalated to 1,250 mg/m2 if severe toxicity was not seen in the previous course. Nineteen of 73 patients (26%) had a partial response (95% confidence interval, 16.5% to 37.6%) in group A. Of 67 patients, 14 (20.9%) showed a partial response (95% confidence interval, 11.9% to 32.6%) in group B. Grade 3 or greater anemia and leukopenia occurred, respectively, in 15 (20.5%) and seven (9.6%) patients in group A and in nine (13.4%) and seven (10.4%) patients in group B. Grade 3 thrombocytopenia was observed in one patient (1.4%). Other toxicities including hepatic toxicity, fatigue, nausea/vomiting, and fever were mild and transient. Pulmonary toxicity was observed in five patients, two of whom died of respiratory insufficiency. The median durations of response were 19.6 weeks in group A and 20 weeks in group B, and median survival times were 44 and 39 weeks, respectively. In conclusion, gemcitabine is an active agent against non-small cell lung cancer with very mild toxicities. These results suggest that gemcitabine has potential utility on an outpatient basis. Further trials in combination with other active agents are warranted.
 ...
PMID:Phase II studies of gemcitabine for non-small cell lung cancer in Japan. 919 79

Many patients with cancer of the stomach or pancreas have locally advanced, unresectable disease at diagnosis or will develop an early local or regional recurrence despite potentially curative surgery. Effective local treatment could increase the proportion of patients able to undergo surgery and decrease locoregional recurrences, which should improve overall survival. External beam radiation (RT) by itself has little effect. Standard treatment, such as RT with concurrent administration of 5-fluorouracil-based chemotherapy as a radiation sensitizer, has, at best, a modest impact on locoregional recurrences and survival. The use of a more effective radiosensitizer might improve the efficacy of local treatment. Paclitaxel synchronizes cells at G2M, the phase of the cell cycle during which cells are most sensitive to the effects of ionizing radiation, and has been demonstrated to sensitize a variety of human cell lines to the effects of RT. In patients with locally advanced non-small cell lung cancer (NSCLC), the Brown University Oncology Group (BrUOG) has demonstrated a high response rate to low-dose weekly paclitaxel with concurrent RT. In addition, we demonstrated that the response to paclitaxel/RT was not affected by mutations in the p53 tumor suppressor gene. This suggested that paclitaxel/RT would be a rational treatment approach for other malignancies with a high frequency of p53 mutations, such as gastric and pancreatic cancers. We have completed a phase I study of weekly paclitaxel and concurrent radiation for locally advanced gastric and pancreatic cancers. The maximum tolerated dose of paclitaxel was 50mg/m2/week for six weeks with 50 Gray (Gy) abdominal radiation. The dose limiting toxicities were abdominal pain, nausea and anorexia. Preliminary response data from ongoing phase II studies suggest that preoperative paclitaxel/RT has substantial activity in patients with locally advanced gastric and pancreatic cancers, though whether this will translate into improved disease-free and overall survival in these patients is not known.
 ...
PMID:Weekly paclitaxel as a radiation sensitizer for locally advanced gastric and pancreatic cancers: the Brown University Oncology Group experience. 920 86

Sixty patients with previously untreated non-small cell lung cancer of stages III and IV were treated with a 210 mg/m2 dose of paclitaxel by means of a 3-hour infusion. The objective response rate was 32% (95% confidence interval, 20-45%): 1 complete response and 18 partial responses. The median duration of response was 15 weeks, and the projected median survival duration of all patients was 30 weeks. Grade 3-4 neutropenia occurred in 73% of patients. Other grade 3-4 adverse events included anemia (5%), vomiting/nausea (8%), peripheral edema (2%), alopecia (7%), elevation of AST (2%), peripheral neuropathy (3%), allergic reaction (2%), arthralgia/myalgia (3%), and interstitial pneumonitis (3%). Paclitaxel administered at 210 mg/m2 by means of a 3-hour infusion every 3 weeks demonstrated a notable activity against previously untreated advanced non-small cell lung cancer, with a 32% major response rate. Major toxicity was neutropenia. Hypersensitivity, neurotoxicity, arthralgia/myalgia and cardiac toxicity were mild and easily managed.
 ...
PMID:Phase II study of 3-hour infusion of paclitaxel in patients with previously untreated stage III and IV non-small cell lung cancer. West Japan Lung Cancer Group. 921 54

Combination chemotherapy with cytotoxic agents is the regular treatment for patients with advanced non-small cell lung cancer (NSCLC), good performance status, and no major clinical contraindications. Since the early 1980s, platinum-based chemotherapy is the cornerstone of this treatment, while combinations containing long-acting alkylating agents have been nearly abandoned, and represent a sort of historical treatment. Nevertheless, the real survival benefits of cisplatin are uncertain and still debated. To attempt an answer, the Cuneo Lung Cancer Study Group (CuLCaSG) carried out a clinical trial comparing a platinum (MVP) versus a non-platinum-based combination chemotherapy (MACC). The study comprised 156 patients with advanced NSCLC randomly assigned to the two treatment arms. MACC and MVP chemotherapies were given as originally described and continued until progression of disease, unacceptable toxicity, or refusal by the patient. For a medium of four cycles of MVP and three cycles of MACC, the median dose intensity (DI) reached was, respectively, 95% and 100% of the intended (P = 0.0132). In all, 27 objective responses (1 complete and 16 partial responses in patients allocated to MVP versus 10 partial responses of the MACC group) were observed. Median progression-free and global survivals were, respectively, 21 and 34 weeks for MVP and 20 and 31 weeks for MACC (non-significant differences). The treatment plan was found non-significant also multivariate analysis of survival. Toxicity was rather similar in the two arms, except for more severe neurological toxicity, anemia, thrombocytopenia, nausea, and vomiting in patients on MVP. Alopecia was more common after MACC. Subjective tolerance to treatment, and perception of physical and psychological well-being were rated similarly by patients of both groups. In conclusion, MVP was moderately more active than MACC, and showed a foreseeable and reversible toxicity, of a low-medium grade. However, this CuLCaSG study failed to substantiate any survival benefit from the use of platinum in combination with other cytotoxic agents.
 ...
PMID:Efficacy of platinum-based regimens in non-small cell lung cancer. A negative report from the Cuneo Lung Cancer Study Group. 926 48

Gemcitabine is a novel nucleoside analog with unique activity against a wide range of solid tumors. We initiated a multicenter phase II study in patients with non-small cell lung cancer (NSCLC) to evaluate the efficacy and safety of gemcitabine. Eligible patients had stage III and IV, previously untreated with chemotherapy, age range from 18 to 80 years, and ECOG performance status 0 2. Gemcitabine was administered at 1000 mg/m2 as a continuous i.v. infusion once a week for a consecutive 3 week period, followed by 1 week of rest. Of the 69 patients enrolled, 67 patients were eligible for efficacy evaluation. The overall response rate was 20.9% with a 95% confidence interval of 11.9-32.6%. The median survival time was 9.0 months and the 12 month survival rate was 31.3%. Grade 3 or 4 toxicities included neutropenia in 22.7%, anemia in 13.4%, leukopenia in 10.4%, anorexia in 10.4%, malaise in 7.5% and nausea/vomiting in 6.0%. Serious toxicities were septic shock and interstitial pneumonia (one patient each). Gemcitabine, administered weekly for three consecutive weeks followed by 1 week of rest, is an active agent for NSCLC. Gemcitabine is currently being evaluated in combination with cisplatin and other agents.
 ...
PMID:Activity of gemcitabine in the treatment of patients with non-small cell lung cancer: a multicenter phase II study. 930 May 71


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>