Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The combination of vindesine and cisplatin is considered a reference regimen in advanced NSCLC which has yielded a significant improvement in the duration of survival. A phase II study of a new semi-synthetic vinca alkaloid, Navelbine, reported an unusually high 29% response rate in stage III-IV NSCLC and a phase I-II study established the feasibility of the combination of Navelbine and cisplatin. We, therefore, designed a prospective randomized trial to compare Navelbine and cisplatin (NVB-P) to vindesine and cisplatin (VDS-P) and to evaluate whether the best of these regimens affords a survival benefit compared to Navelbine alone (NVB), an outpatient regimen. Forty-five centers included 612 patients in this study: 206 in NVB-P, 200 in VDS-P and 206 in NVB. Navelbine was given at a dose of 30 mg/m2 weekly, cisplatin at 120 mg/m2 on day 1, day 29 and then every 6 weeks and vindesine at 3 mg/m2 weekly for 6 weeks and then every other week. Treatment was continued until progression or toxicity. Patients' characteristics were similar in the three groups with 59% of patients presenting with metastatic disease. An objective response rate was observed in 30% of patients in NVB-P versus 19% in VDS-P (P = .02) and 14% in NVB (P < .001). The median duration of survival was 40 weeks in NVB-P compared to 32 weeks in VDS-P and 31 weeks in NVB. The comparison of survival between the three groups demonstrated an advantage for NVB-P compared to VDS-P (P = .04) and NVB (P = .02). Neutropenia was significantly higher in the NVB-P group (P < .001) and neurotoxicity more frequent with VDS-P (P < .004). Since our results have demonstrated that NVB-P yields a longer survival duration and a higher response rate than VDS-P or NVB alone, with acceptable toxicity, this combination should be considered a reference regimen in advanced NSCLC.
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PMID:[Results of a randomized study comparing combination of navelbine-cisplatin to combination of vindesine-cisplatin and to navelbine alone in 612 patients with inoperable non-small cell lung cancer]. 868 91

The present pilot study included 31 evaluable patients with metastatic breast cancer. All patients had disease progression following first-line treatment for their metastatic disease (by hormonal treatment or chemotherapy). Twenty patients had previously received Adriamycin as either adjuvant or palliative treatment. The patients were treated by Navelbine 25 mg/m2, Mitoxantrone 6 mg/m2 (both drugs on days 1 and 8) with 5-Fluorouracil (5-FU) 300 mg/m2 as continuous 24-hour infusion on days 1 to 14, and to be recycled on day 29. The overall response rate was 58%, and 50% for those who had received prior Adriamycin. The median time to progression was 8.5 months and the 1-year survival rate for the whole group was 45%. Grade III or IV neutropenia was the dose-limiting toxicity being encountered in 28% of the treatment courses with toxic death in 1 patient.
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PMID:Treatment of metastatic breast cancer by navelbine, mitoxantrone and continuous infusion 5-fluorouracil (FMN regimen): results of a pilot study. 880 59

Thirty-three metastatic breast cancer patients with prior chemotherapy (adjuvant alone, 9 patients; chemotherapy for metastatic disease alone, 13 patients; chemotherapy for both, 11 patients) received paclitaxel (Taxol) 135 mg/m2 over 1 h followed by vinorelbine (Navelbine) 30 mg/m2 over 10 minutes on day 1 every 3 weeks. All patients had contraindications to receive anthracycline therapy (primary resistance, 10 patients; dose reaching the maximum recommended dose and/or myocardiopathy, 23 patients). Twenty-eight patients had previously received anthracyclines, and the remaining 5 had received prior CMF (cyclophosphamide, methotrexate, fluorouracil). The combination of paclitaxel plus vinorelbine was given as first-line chemotherapy for metastatic disease to 9 patients and as second- or third-line to the remaining 24 patients. The mean number of metastatic sites was 2 (range 1-5). Twenty-two patients had visceral involvement. Overall, 3 complete and 13 partial responses were observed among the 33 patients (objective response rate 48.5%, 95% confidence interval 31% to 66.5%). The response rate in patients receiving the regimen as first-line chemotherapy was 67% (6/9 patients), compared to 42% (10/24) in those receiving the regimen as second- or third-line chemotherapy. Primary anthracycline-resistant patients showed a response rate of 60% (6/10), whereas the remaining patients had a response rate of 43.5% (10/23). The main toxicities were grade 3 alopecia (92%), grade 3-4 neutropenia (28%), neutropenic fever (16%), grade 1-2 peripheral neuropathy (44%), arthralgias-myalgias (32%), and hypersensitivity reactions (8%). Phlebitis was a significant clinical problem in patients receiving the drugs through a peripheral vein.
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PMID:Paclitaxel plus vinorelbine in metastatic breast Ca patients with contraindications to receive anthracyclines. 951

Twenty patients (13 males, 7 females, median age 61 years, range 27-74) with recurrent adenocarcinoma-like tumors of major (10 patients) and minor (10 patients) salivary gland origin (13 adenoid cystic carcinoma, 5 adenocarcinoma, 1 malignant mixed tumor, 1 undifferentiated carcinoma) were treated with vinorelbine at the dose of 30 mg/m2 i.v. weekly. Sixteen patients had been previously treated with surgery + radiation, 3 with surgery + radiotherapy + Novantrone and 1 with radiotherapy alone. Nine patients had local recurrence, 2 local relapse + metastasis and 9 metastasis alone. Site of metastases are: lung (7), bone (1), lung + bone (2), lung + bone + lymph-node + skin (1). Overall 174 courses were given (median 9, range 6-19). Responses were: PR in 4 patients (20%) with a median duration of 6 months (3-9), 9 NC (45%) with a median duration of 3.5 months and 7 PD (35%). The median survival time was 10 months for PR/NC patients, 4 months for non-responders. Median overall survival was 7 months. Vinorelbine has a moderate activity in these very advanced cases.
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PMID:Vinorelbine treatment of recurrent salivary gland carcinomas. 983 66

The optimal therapy for locally advanced, unresectable, stage III non-small-cell lung cancer (NSCLC) continues to evolve. The critical determinants of overall survival include local tumor control and the eradication of subclinical micrometastatic disease. Historically, standard radiation therapy resulted in a median survival of 7 to 10 months. In a randomized trial, the Cancer and Leukemia Group B (CALGB) established the superiority of induction cisplatin (Platinol) and vinblastine chemotherapy followed by radiation therapy. Additional studies revealed that induction chemotherapy improved survival rates by decreasing metastatic disease progression. Three independent meta-analyses confirmed the survival benefit afforded by cisplatin-based induction chemotherapy followed by radiotherapy, and helped to establish this as the new standard of care. Other investigators have demonstrated improvements in local tumor control and survival with either concurrent chemoradiotherapy or hyperfractionated radiotherapy. Most recently, attention has focused on radiation dose intensity and the utilization of newer, highly active chemotherapeutic agents with concurrent or sequential radiation therapy. These newer drugs, including paclitaxel (Taxol), docetaxel (Taxotere), gemcitabine (Gemzar), vinorelbine (Navelbine), and irinotecan (Camptosar), enhance radiation cytotoxicity and, when administered in systemically active dosages, may also control micrometastatic disease. Phase I and II studies of novel chemoradiation regimens continue to demonstrate encouraging results, and several large randomized clinical trials are currently enrolling patients.
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PMID:Chemoradiation for locally advanced, unresectable NSCLC. New standard of care, emerging strategies. 1049 43

Lung cancer is the leading cause of cancer death in the United States. Surgery is the treatment of choice for early stage patients. Despite radical surgery, patients with early stage lung cancer remain at risk for recurrence. The role of adjuvant therapy remains to be clearly defined. Locally advanced non-small-cell lung cancer is too extensive for surgical resection, yet does not show evidence of metastatic disease. Historically, these patients were treated with radiation alone. More recent studies have provided the rationale for combining radiation with chemotherapy for patients with good performance status who have locally advanced disease. For patients with marginally resectable tumors, treatment is often given preoperatively (neoadjuvant) as a means of shrinking the tumor to make it resectable. In patients with clearly unresectable disease, radiation with chemotherapy has been established as better than either modality alone. Palliative radiation alone can be used for patients who cannot tolerate this aggressive approach. The optimal sequencing, as well as the best chemotherapeutic agent to use, remains under investigation. Some of the newer agents showing promise in the treatment of non-small-cell lung cancer include paclitaxel (Taxol) and carboplatin (Paraplatin). Other agents that are currently under investigation include topotecan, gemcitabine, and vinorelbine (Navelbine).
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PMID:The role of radiation, with or without chemotherapy, in the management of NSCLC. 1055 Aug 32

The incidence of esophageal cancer continues to increase due to a rapid increase in adenocarcinoma of the distal esophagus and gastroesophageal junction. At least 50% of patients present with metastatic cancer and most patients with localized disease will develop metastases despite potentially curative local therapy. Thus, the majority of esophageal cancer patients will become candidates for palliative chemotherapy. Traditionally, single agents effective in this disease have included cisplatin, 5-fluorouracil, and mitomycin. The combination of cisplatin and continuous-infusion 5-fluorouracil is the standard for both squamous cell carcinoma and adenocarcinoma, with a 25% to 35% response rate in metastatic disease. More recently, paclitaxel has shown favorable results as a single agent or in combination with cisplatin in both disease histologies. One-hour weekly paclitaxel, a promising schedule with little toxicity, is under active investigation. Weekly irinotecan and cisplatin is a highly effective new regimen in both adenocarcinoma and squamous cell carcinoma with relatively little toxicity. Vinorelbine has demonstrated response in squamous cell carcinoma and has less toxicity than its predecessor, vindesine. Use of newer agents in combination with concurrent radiotherapy in locally advanced disease is the subject of ongoing clinical trials.
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PMID:Chemotherapy in esophageal cancer. 1056 6

We studied a cohort of 120 patients with inoperable non-small-cell lung cancer treated with vinorelbin at the dose of 25-30 mg/m2/week in a single drug chemotherapy regimen. Surgery was contraindicated due to staging or to concomitant morbidity. Twenty patients survived 18 months or more. One survivor responded exceptionally, surviving 120 months. The mean dose intensity of Vinorelbine in long-term survivors was 21 mg/m2/week. Objective response was found at multivariate analysis to be a prognostic factor for survival beyond 18 months. Weight loss (< 5 kg) was an unfavorable prognostic factor in patients with metastases.
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PMID:[Non-small-cell bronchial cancers: long-term survival after single drug chemotherapy with vinorelbine]. 1057 48

This study reports the results of 120 patients with inoperable non-small cell lung cancer treated with Navelbine at a dose of 25-30 mg/m(2)/week in a single-drug chemotherapy regimen. Surgery was contraindicated due to staging or to concomitant morbidity. Twenty patients achieved survival greater than or equal to 18 months, and one patient obtained exceptional survival of more than 120 months. The mean dose intensity of Navelbine in long-term survivors was 21.61 mg/m(2)/week. Objective response to Navelbine was found by multivariate analysis to be a prognostic factor for survival beyond 18 months. Weight loss of more than 5 kg of corporal weight was an unfavorable prognostic factor in patients with metastatic disease.
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PMID:Non-small cell lung cancer: a study of long-term survival after vinorelbine monotherapy. 1079 2

The objective of the present study was to determine the pharmacokinetic profile of vinorelbine in patients 65 years or older with metastatic cancer in progression. Twelve patients were enrolled in this study. Vinorelbine was administered by a 10-min continuous infusion at a dose of 20-30 mg/m2 through a central venous catheter. Chemotherapy was repeated weekly. A total of 46 courses of vinorelbine was studied. Each patient underwent pharmacokinetic evaluation during the first cycle of treatment. Toxicity evaluation was carried out before each course of chemotherapy. Plasma vinorelbine determinations were performed by high-performance liquid chromatography with spectrofluorometric detection. A Bayesian estimation of individual pharmacokinetic parameters was carried out using the nonlinear mixed-effect modeling approach as implemented in the NONMEM computer program. An open three-compartment pharmacokinetic model with a zero order input rate was used to describe the kinetics of vinorelbine. Area under the plasma-concentration time curve (AUC) normalized to a 30 mg/m2 administered dose averaged 0.89 mg/liter x h (coefficient of variation = 23.7%). The total plasma clearance averaged 0.93 liter/h/kg (0.61-1.83 liter/h/kg; coefficient of variation = 38.6%). The elimination half-life was 38.1 +/- 5.8 h. A high correlation was found between patient age and total clearance (r = -0.8; P < 0.001). The main hematological toxicity observed was anemia in 11 patients. Neutropenia occurred in 50% of patients. Significant correlations were found between AUC and the decrease in the hemoglobin level (r = 0.60) and between AUC and the decrease in the neutrophil count (r = 0.66). Thrombocytopenia was observed in only one patient. In conclusion, the age-related decrease in clearance found in this study supports the design of a Phase I study of vinorelbine in patients older than 65 years or perhaps 70 years.
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PMID:Bayesian estimate of vinorelbine pharmacokinetic parameters in elderly patients with advanced metastatic cancer. 1091 11


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