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

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

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

In recent years, the clinical application of paclitaxel (Taxol), docetaxel (Taxotere), vinorelbine (Navelbine), and trastuzumab (Herceptin) has improved the management of advanced breast cancer. With the introduction of gemcitabine, a new drug with significant activity in breast cancer has become available. As a single agent, gemcitabine (Gemzar) provides response rates in the range of 25% to 46% in breast cancer, depending on starting dose and status of prior chemotherapy for metastatic disease. Higher response rates are observed when gemcitabine is combined with other classes of cytotoxic drugs. Studies conducted in our laboratory detected high degrees of synergy between gemcitabine and cisplatin (Platinol) in a variety of human tumors in primary culture. These analyses identified breast cancer as a target for this combination. The combination of cisplatin plus gemcitabine is active in relapsed breast cancer patients. The activity observed in drug-resistant patients suggests relative non-cross resistance with other drug combinations.
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PMID:Gemcitabine plus cisplatin in breast cancer. 1125 86

The purpose of this study was to evaluate short-term adverse effects and determine a safe dosage for vinorelbine (Navelbine)--a new semisynthetic vinca alkaloid--in dogs with malignant tumors. Nineteen dogs were treated with vinorelbine as a 5-minute IV infusion every 7 days at starting dosages ranging from 10 to 20 mg/m2. The median number of treatments per dog was 7 (range, 1-11). The maximum tolerated dosage varied between 15 and 18 mg/m2, and a starting dosage of 15 mg/m2 is recommended. Neutropenia was the dose-limiting toxicity. Although efficacy was a secondary endpoint of this dosage-finding study, 2 dogs with metastatic bronchoalveolar carcinoma experienced a partial response for an overall response rate of 12.5% in 16 dogs with gross measurable disease. Three dogs with microscopic disease were treated (incompletely excised bronchoalveolar carcinoma or lymph node metastatic disease). Two died of pulmonary metastatic disease 113 and 196 days posttreatment, and 1 is still alive after at least 730 days. The well-tolerated toxicity profile and clinical activity observed in dogs with bronchoalveolar carcinoma warrants further investigation.
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PMID:Toxicity, dosage, and efficacy of vinorelbine (Navelbine) in dogs with spontaneous neoplasia. 1532 May 94

Eribulin mesylate (Halaven-Eisai) has been approved by the FDA for treatment of patients with metastatic breast cancer who have previously received at least 2 chemotherapy regimens for metastatic cancer. Prior therapy should have included an anthracycline and a taxane in either an adjuvant or metastatic setting. Other drugs used to treat anthracycline- and taxane-refractory metastatic breast cancer include capecitabine (Xeloda), gemcitabine (Gemzar, and others) and vinorelbine (Navelbine, and others).
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PMID:Eribulin mesylate (Halaven) for breast cancer. 2150 35

Vinorelbine (VNR; 5'-nor-anydro-vinblastine) is a new semisynthetic vinca alkaloid which has demonstrated significant clinical activity against non-small cell lung cancer, bronchial adenocarcinoma, breast cancer, and head/neck squamous cell carcinoma. Moreover, vinorelbine has been widely employed in combination with cisplatinum with or without 5-fluorouracil for the treatment of lung cancer and head/neck carcinomas. Sixteen consecutive patients with lung metastases from colorectal adenocarcinomas were treated with vinorelbine tartrate (Navelbine R) given at the dose of 25 mg/m(2) i.v. bolus every week for eight consecutive times employing metoclopramide as an antiemetic tool. All patients had previous surgery, two had adjuvant chemo-immunotherapy with i.v. 5-fluorouracil and oral levamisole, 5 patients had adjuvant radiotherapy, and 1 patient had chemotherapy with levofolinic acid and 5-fluorouracil for advanced disease. Sites of disease included lung in all cases, liver metastases in 3 patients and nodal tumoral deposits in 2 cases. All patients entered in the study had lung disease as predominant site of disease and showed multiple metastases. One patient was not evaluable for response, toxicity and survival because he was lost to follow-up before completion of therapy. No major objective response was seen. Four patients had stable disease which lasted a mean of 5.2 months, and the remaining 11 patients showed progressive disease. Mean survival was 6.7+ months (range 4.0-12.0+ months). The treatment was quite well tolerated by most patients, granulocytopenia being the most frequent side-effect. Nausea/vomiting was very mild with grade 1 episodes in 5 patients (33%). Grade 1 leukopenia was seen in 5 patients (33%), grade 2 leukopenia in 3 patients (20%), and grade 3 in 2 cases (13%). Grade 1 thrombocytopenia was recorded in 3 cases (20%). No significant neurotoxicity was observed, except mild constipation in 4 cases (26%). The activity of VNR on a weekly schedule against lung metastases from large bowel adenocarcinoma is very low, however it should be noted that the treatment was well tolerated by most patients.
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PMID:Single agent vinorelbine in the treatment of unresectable lung metastases from colorectal cancer. 2159 13


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