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)

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

S 23906-1 is a novel acronycine derivative selected on the basis of its potency in vitro. We investigated the antitumor activity of S 23906-1 against several murine transplantable tumors (C38 colon carcinoma, P388 leukemia, B16 melanoma, and Lewis lung carcinoma) and in orthotopic models of human lung (NCI-H460 and A549), ovarian (IGROV1 and NIH:OVCAR-3), and colorectal cancers (HCT116 and HT-29). Against established C38 colon carcinoma, S 23906-1 administered twice i.v. from 1.56-6.25 mg/kg markedly inhibited tumor growth. Treatment at the optimal dose (6.25 mg/kg) induced tumor regression in all of the mice. Acronycine was 16-fold less potent and only moderately active at the maximum tolerated dose, 100 mg/kg. Against other murine tumors of the former National Cancer Institute panel, S 23906-1 was either only moderately active or totally inactive. When evaluated in human orthotopic models, S 23906-1 given p.o. or i.v. demonstrated a marked antitumor activity against human carcinomas. In the two human lung cancer models, S 23906-1 increased the survival of the animals in a dose-dependent manner and induced treated versus control values of 162% (NCI-H460) and 193% (A549). Vinorelbine was less active, with treated versus control values of 119% and 174%, respectively. A significant survival benefit was also observed against the two i.p. ovarian tumors in which S 23906-1 was as active as paclitaxel, inducing 80% long-term survivors in the NIH:OVCAR-3 model. Lastly, S 23906-1 inhibited the growth of primary HT-29 and HCT116 colon tumors grafted onto the cecum as efficiently as irinotecan and eradicated the formation of lymph node, hepatic, and pulmonary metastases in the aggressive HCT116 model. The novel spectrum of activity of S 23906-1 compared with existing anticancer agents warrants further preclinical investigation.
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PMID:Marked antitumor activity of a new potent acronycine derivative in orthotopic models of human solid tumors. 1148 41

Vinorelbine (VNR) is a semi-synthetic vinca alkaloid (5'nor-anhydro-vinblastine) that differs from other vinca alkaloids by a modification of the catharantine moiety of the molecule. VNR binds to tubulin and inhibits tubulin assembly and microtubule formation. It has less activity than other vinca alkaloids against axonal microtubules and this may account for its reduced neurotoxicity in clinical use. In gastrointestinal tumours, VNR did not show significant activity in advanced pancreatic adenocarcinomas. Two phase II studies in metastatic colorectal cancer resulted in conflicting results: no activity in first-line therapy on lung metastases, but encouraging results in 5-fluorouracil (5-FU)-resistant metastases. Conversely, significant antitumoural effect in oesophageal squamous cell carcinoma has been demonstrated. The first study was performed in 46 patients with metastatic disease. Six of 30 patients (20%) without prior chemotherapy achieved a partial response (95% confidence interval (CI), 8-39%). One of 16 (6%) with prior chemotherapy responded. Grade (gr) 3 or 4 granulocytopaenia occurred in 59% of patients and peripheral neurotoxicity was minor (26% gr 1). These results were confirmed by another group. A phase I study was performed using VNR and concurrent radiation (64 Gy) in previously untreated patients with inoperable locally advanced oesophageal cancer ineligible for cisplatin-5-FU-based chemoradiation. Twenty-four patients entered the study. The maximal tolerated dose has been reached at 25 mg/m(2)/week, the dose-limiting toxicities being febrile neutropaenia and infection. Major objective tumour response was observed at each dose level except the first one. Recruitment is ongoing to confirm the recommended dose of VNR (20 mg/m(2)/week). A phase II study of a VNR-cisplatin combination in metastatic oesophageal squamous cell carcinoma was recently completed. Seventy-one eligible patients were included. Main toxicities were haematological (gr 3-4 granulocytopaenia, 41%), infection, vomiting and fatigue. The response rate was 37% (95% CI, 26-49%) with a median duration of response of 7.7 months. This 2-day regimen appears at least as active and less toxic than the standard 5-day 5-FU and cisplatin regimen.
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PMID:Activity of vinorelbine in gastrointestinal cancers. 1200 75

The treatment of advanced non-small cell lung cancer requires histologic proof of diagnosis, careful staging, and assessment of each patient's performance status and comorbidities. For patients with stage IIIB (pleural effusion) and stage IV disease who have a Cancer and Leukemia Group B performance status (PS) of 0 to 1, appropriate management consists of combination chemotherapy with a platinum (either cisplatin or carboplatin) combined with paclitaxel, gemcitabine, vinorelbine, docetaxel, or CPT-11. Dosages and schedules previously established by large phase II or phase III studies should be followed. Variations in the toxicity patterns, schedules of administration, and economic considerations should guide the selection of the specific regimen. For patients who maintain a good performance status after first-line chemotherapy, second-line treatment may be considered. Current evidence supports the use of docetaxel as second-line treatment if the patient has not previously received this drug. Gemcitabine and paclitaxel may also have activity in this setting. Vinorelbine, ifosfamide, and CPT-11 appear to be inactive as second-line therapy for patients who have previously received platinum-based chemotherapy. For patients with a PS of 2, single-agent chemotherapy with vinorelbine, gemcitabine, or a combination of the two should be considered. Patients with poor performance status should be treated with supportive measures designed to relieve pain and acute complications because any tumor-directed therapy has limited benefit. Special situations exist in which curative therapy for metastatic disease is a possibility. Patients who present with solitary sites of metastatic disease, particularly after a long disease-free interval and in the CNS may undergo definitive surgery or radiotherapy with curative intent. Some have also reported favorable outcomes for patients with solitary adrenal or bone metastases as well. Surgical treatment or definitive radiotherapy should not be employed unless a thorough restaging evaluation is performed that includes computed tomography scan of the chest and abdomen through adrenals, brain magnetic resonance imaging, and positron emission tomography scan. A plethora of new agents targeting angiogenesis, tumor invasiveness, the hypoxic environment of tumors, and the cell cycle are currently in development.
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PMID:Advanced non-small cell lung cancer. 1205 40

Esophageal cancer is uncommon, but its incidence is rapidly increasing in the Western countries because of the high incidence of the cardia esophageal adenocarcinoma. Notwithstanding the encouraging results achieved with surgical procedures, esophageal carcinoma has a poor prognosis with 5-year survival in 10% of cases without differences between both squamous and adenocarcinoma histologies. Almost 50% of esophageal cancer patients have unresectable disease at presentation; in the past years combined modality treatments, using chemotherapy and/or radiotherapy with or without surgery, have been evaluated to reduce the risk of local and/or distant recurrences. Ongoing regimens with new agents (Taxanes, Vinorelbine, Irinotecan), in association or not with platinum compounds, show good antitumor efficacy and tolerability, even in the metastatic disease. Preoperative strategies with radiation only did not give any advantage compared to surgery alone, instead, controversial results were obtained, with a minimal advantage, using chemotherapy. Combined chemotherapy and radiation, in suitable candidates for resection has shown an improvement of complete pathological responses, in both the histologies, but with superior toxicities when compared to chemotherapy or radiation therapy alone. Postoperative adjuvant therapies as radiation, chemotherapy or both, have not led to a marked improvement in overall survival and should be performed only in clinical trials. The use of chemoradiotherapy showed a clear advantage versus radiotherapy alone and in many cases equivalent to regimens plus surgery even if control studies haven't been performed. Clinical trials with novel biologic agents, in combination to chemotherapy or alone, against cell growth arrest, neoagiongenesis and tumor metastasis invasion process are currently under evaluation. In the coming years new markers as antigen Ki-67 determination, p53 mutation or high levels activity of thymidylate synthase and novel staging techniques as PET could be precious to identify the better treatment for each patient.
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PMID:[New strategies in the treatment of esophageal cancer]. 1259 16

Vinorelbine and docetaxel are two effective drugs in esophageal cancer; our purpose was to evaluate efficacy and toxicity of a combination of these drugs in recurrent squamous cell esophageal cancer. Twenty patients previously treated with concomitant chemoradiotherapy (n = 14), surgery alone (n = 2), surgery plus radiotherapy (n = 2), or concomitant chemoradiotherapy + surgey (n = 2) were enrolled. Thirteen patients had a local-regional recurrence, two patients had metastases, and five patients had both. The doses were 80 mg/m(2) for docetaxel and 20 mg/m(2) for vinorelbine on d 1 every 21 d for a maximum of six cycles. Twenty patients received a total of 106 cycles (median per patient, 5). Neutropenia was the most frequent and severe side effect (grade 4 in 80%; grade 3 in 20%). The overall response rate was 60%, which included 3 of 20 complete responses (15%) and 9 of 20 partial responses (45%). Median response duration was 7 mo (2-50+). Overall median survival was 10.5 mo (range, 2-55+). A dysphagia improvement was observed in 81% of patients. In conclusion, the data from this phase II study indicate that this combination is effective in recurrent heavily pretreated patients with a short-lasting manageable toxicity.
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PMID:Docetaxel and vinorelbine: an effective regimen in recurrent squamous cell esophageal carcinoma. 1266 80

A phase II study was conducted to assess the toxicity and response rate of vinorelbine (NavelbineR) combined with epirubicin and fluorouracil (NEF) in metastatic breast cancer. Vinorelbine was delivered at a dose of 25 mg/m2 on days 1 and 8, epirubicin at 60 mg/m2 on day 1 and fluorouracil at 600 mg/m2 on day 1, at 3-week intervals. Forty consecutive ambulant patients with breast cancer with measurable metastases were treated with a total of 310 cycles (median 8) as first-line therapy. The objective response rate was 83% (95% CI 71-95) (6/40 CR 15%, 27140 PR 68%). In 3 patients, CNS metastases were detected during NEF therapy those who had a partial response in their visceral metastases. Median time to progression was 13 months (95% CI 7-19) and estimated median survival time was 32 months. The main dose-limiting adverse effect, grade III-IV haematological toxicity, was reported in 92% of patients. One patient died of neutropenic sepsis. Grade III infections requiring hospitalization were observed in 8 patients (20%). Half of the patients complained of mild constipation, nausea or stomatitis, which were easily managed. Almost all patients had grade III alopecia. One patient with previous adjuvant anthracycline therapy (CEF x 9 two years earlier) developed fatal grade IV cardiac failure associated with pulmonary emboli 2 months after completion of NEF therapy (PR with 6 cycles). In line with the observations of others conducting phase II first-line trials combining vinorelbine and epirubicin, it is concluded that the NEF regimen is effective in metastatic breast cancer. Haematological toxicity, however, requires dose reductions in many patients. Furthermore, careful monitoring of cardiac function is necessary, particularly in patients who received prior adjuvant anthracycline therapy.
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PMID:Vinorelbine, epirubicin and fluorouracil as first-line therapy in metastatic breast cancer--a phase II trial. 1289 2

Paclitaxel and vinorelbine are two drugs active against breast cancer. A phase II study was initiated with the aim of assessing the efficacy and feasibility of the combination. Twenty-six patients presenting with advanced breast cancer with a taxane- and vinorelbine-free line of chemotherapy were included and treated with vinorelbine (20 mg/m2 on D1, D15), followed by paclitaxel (175 mg/m2 on D1), every 3 weeks. A 48% (95% CI: 35-61) response rate was obtained in the 23 patients evaluable for response. Vinorelbine was administered on D15, as scheduled, in 72% of cycles. The main toxicity observed was grade III to IV neutropenia in 73% of patients. Febrile neutropenia was reported in three patients. Disease-free survival was 118 days, and overall median survival was 361 days. This combination of paclitaxel and vinorelbine is feasible and effective in patients with early relapse or previously treated with first-line chemotherapy for metastatic disease.
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PMID:Phase II study of paclitaxel combined with vinorelbine in patients with advanced breast cancer. 1517 Jan 56

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

A 60-year-old woman with Stage II, ER-positive, PgR-positive, HER2 (2+) cancer in the right breast underwent right mastectomy with right axillary dissection after chemotherapy with EC followed by docetaxel (DOC) alone. Exemestane was used for postoperative adjuvant treatment. She underwent a right chest wall tumor resection for local recurrence. Hormone therapy was continued with toremifene in place of exemestane. In December 2007, two years after the second surgery, CEA was elevated and PET showed a local recurrence in the right chest wall and metastases to the right axillary nodes and liver. The tumor was ER-positive, PgR-negative and HER2 (3+) at recurrence, and vinorelbine/trastuzumab combination was initiated as first-line chemotherapy for the recurrent lesion and liver metastasis. All lesions in the right chest wall, right axillary nodes and liver disappeared from PET and CT images after five courses of the regimen, resulting in clinical CR. Vinorelbine combined with trastuzumab appears to be a useful therapy for HER2-positive recurrent breast cancer.
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PMID:[A case of recurrent breast cancer responding to vinorelbine/trastuzumab combination therapy]. 2000 69


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