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 role of chemotherapy in the treatment of non-small cell lung cancer (NSCLC) has increased greatly in the past few years. While cytotoxic drugs are currently used both as single agents and in combination for palliation in locally advanced and metastatic disease, they have also been incorporated into multi-modality treatment strategies of Stage I to Stage III NSCLC. One of the main reasons for the increased acceptance of chemotherapy is the development of new substances. Among the most promising of these new drugs is the antimetabolite gemcitabine. Several single-arm gemcitabine Phase II studies involving more than 400 patients show validated response rates in more than 20% of the patients. These positive results have also been confirmed in randomized Phase II studies. Gemcitabine's unique mechanism of action, its lack of overlapping toxicity with other agents, and its favorable toxicity profile also define it as an ideal candidate for combination therapy. The activity seen with single-agent gemcitabine therapy can be compared with that of cisplatin-etoposide combination therapy. Gemcitabine-cisplatin combination response rates range from 31% to 54%, with a median survival time between 8.4 and 15.4 months and a 1-year survival rate between 30% and 59%. In addition to the clinical research of gemcitabine-cisplatin combinations, gemcitabine has also been tested in various double and triple combinations with carboplatin, paclitaxel, docetaxel, vinorelbine, and ifosfamide. Investigations combining gemcitabine with radiation therapy are on-going. The following review will summarize results from representative Phase I/II and III studies using gemcitabine for NSCLC patients.
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PMID:Gemcitabine in non-small cell lung cancer (NSCLC). 1083 Jan 39

Pancreatic cancer constitutes less than 2% of all cancers diagnosed in Singapore, consistent with the proportion described worldwide. About 40% of patients are diagnosed when the disease is locally advanced but without metastases. Another 40% are diagnosed with distant metastases. Only 20% are diagnosed when resectable. Most are adenocarcinomas arising from the head of the pancreas. Systemic chemotherapy is used for advanced metastatic pancreatic cancer but has met with limited success. Gemcitabine is a new fluorine-substituted cytarabine compound. In a randomised study it appears to confer statistically significant, although modest, improvement in quality of life and survival of patients with metastatic pancreas cancer. Evaluation of the drug in combination chemotherapy regimens and with radiation continues.
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PMID:Clinical update of gemcitabine in pancreas cancer. 1089 97

The effectiveness of different regimens of chemotherapy for advanced pancreatic cancer was compared in 74 cases (1995-1999). 5-fluorouracil (5FU), adriamycin and mitomycin C (FAM) were given to 12 patients, 5FU alone--23, 5FU plus leukovorin--29, and gemcitabine alone--10. Metastases to the liver were detected in 42 (57%) patients. Partial response (40) was registered in: FAM--1 (8%); 5FU--1 (4%); 5FU + leukovorin--3 (10%); gemcitabine--3 (30%). Mean duration (40) was 5.4; 4; 6.1 and 9 months, respectively. Stabilization was recorded in 17 (23%), mean duration--4.4 months; tumor progression--49 (66%). Toxic side-effects of all the regimens were insignificant. Mean survival rates following FAM, 5FU, 5FU + leukovorin were 4.4; 4.2 and 5.6 months, respectively, while that for gemcitabine varied 3-24 months (on average--7.9 months). Survival in patients responsive to chemotherapy was 9.8; remaining patients--4.7 (p (0.05). Chemotherapy for advanced pancreatic carcinoma is a measure of palliation; its use was followed by a 20% increase in survival. Gemcitabine treatment appeared most effective.
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PMID:[Experience with chemotherapy for advanced pancreatic carcinoma]. 1120 97

A phase II study was performed to investigate the efficacy and tolerability of gemcitabine as third-line chemotherapy for patients with metastatic breast cancer, previously treated with both an anthracycline- and taxane-containing regimen. Twenty-three patients were treated with gemcitabine 1200 mg/m2 in a 30-min infusion on day 1, 8 and 15 of a 28 day cycle. Seventy-four percent of the patients had visceral metastases. No complete or partial responses were observed. Six patients (26%) had stable disease with a median duration of 4.0 months. The median time to progression was 1.9 months and the median survival time was 7.8 months. Neutropenia grade 3 and 4 was observed in four patients (18%). Non-hematological toxicity grade 3 included nausea and vomiting in 14%, skin toxicity in 9% and elevation of transaminases in 23% of the patients. Gemcitabine is ineffective as third-line single agent therapy in patients failing anthracycline and taxane treatment for metastatic breast cancer.
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PMID:Phase II study of weekly gemcitabine in patients with metastatic breast cancer relapsing or failing both an anthracycline and a taxane. 1136 14

Gemcitabine is a promising new agent that has been recently studied for palliation of advanced (stage IV) unresectable pancreatic cancer. We hypothesized that adjuvant gemcitabine would reduce recurrence and metastases following surgical resection of pancreatic cancer. To test this hypothesis, we evaluated gemcitabine on a green fluorescent protein (GFP) transductant of the human pancreatic cancer cell line BxPC-3 (BxPC-3-GFP) using surgical orthotopic implantation (SOI) in nude mice. GFP enabled high resolution fluorescent visualization of primary and metastatic growth. Five weeks after SOI, the mice were randomized into three groups: Group I received exploratory laparotomy only. Group II underwent surgical resection of the pancreatic tumor without further treatment. Group III underwent tumor resection followed by adjuvant treatment with gemcitabine, 100 mg/kg every three days for a total of four doses, starting two days after resection. The mice were sacrificed at thirteen weeks following implantation and the presence and location of recurrent tumor was recorded. Gemcitabine reduced the recurrence rate to 28.6% compared to 70.6% with resection only (P = 0.02) and reduced metastatic events 58% in the adjuvant group compared to resection only. This study, demonstrating that gemcitabine is effective as adjuvant chemotherapy post-pancreatectomy, suggests this new indication of the drug clinically.
Clin Exp Metastasis 2000
PMID:Antimetastatic efficacy of adjuvant gemcitabine in a pancreatic cancer orthotopic model. 1146 69

The necessity of improving the long-term survival of patients with locally advanced non-small cell lung cancer (NSCLC) points out on the one hand the limit of surgery alone and, on the other hand, the need of combined modality therapy, in which the role of chemotherapy to control distant metastases is prominent. Recent experiences support the efficacy of neoadjuvant chemotherapy with or without radiotherapy. Phase II studies show response rates of 50-80% and median survival longer than 2 years. Phase III studies suggest that neoadjuvant chemotherapy improves survival and objective responses, and induces higher percentages of complete resections compared with surgery alone or chemotherapy and radiotherapy. The gemcitabine-cisplatin regimen has proved its efficacy in NSCLC advanced disease with response rate greater than 40% in phase II and III trials. Representing one of the regimens most used in Europe, its activity has been investigated also in the neoadjuvant setting. Phase II studies have reported an average response rate greater than 60%, complete surgical resections in 60-70% of the cases, and 1-year survival of about 60%. A modern tendency is to use neoadjuvant chemotherapy in very early stages of NSCLC. Gemcitabine-cisplatin regimen has been used as a randomised clinical trial (chemotherapy for early stages trial, CHEST) to compare the efficacy of surgery alone versus surgery plus preoperative chemotherapy in early-stage disease (T2-3N0, T1-2N1, T3N1), and to evaluate the progression free survival.
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PMID:Induction chemotherapy with gemcitabine and cisplatin in stage III non-small cell lung cancer. 1174 99

Gastrointestinal tumors are among the most common cancers in the world. Palliative chemotherapy is widely used to treat patients with advanced or metastatic disease. The mainstay of chemotherapy for colorectal cancer is 5-fluorouracil (5-FU) modulated by leucovorin (LV), alone or in combination with oxaliplatin or irinotecan (CPT-11). Gemcitabine is currently the standard of care in patients with pancreatic cancer. There is no standard in gastric cancer, although cisplatin, 5-FU, and the anthracyclines are the most common drugs used. Pemetrexed, a new-generation antifolate antimetabolite, has demonstrated a 15% to 17% response rate in metastatic colorectal cancer, similar to those of other single agents in previously untreated patients. In patients with advanced pancreatic cancer, pemetrexed achieved a 6% response rate and a 28% 1-year survival rate, which is comparable to single-agent gemcitabine. Preliminary results in gastric cancer are encouraging. The generally mild side effect profile of pemetrexed, especially with folate supplementation and dexamethasone premedication, and the synergy between pemetrexed and drugs frequently used in gastrointestinal cancers, such as irinotecan, oxaliplatin, and gemcitabine, suggest that further clinical studies are indicated to determine the role of pemetrexed in the treatment of colorectal, pancreatic, and gastric cancers.
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PMID:Pemetrexed in patients with gastrointestinal carcinoma. 1202 92

Neoadjuvant chemotherapy has become a standard treatment in the management of locally advanced breast cancer. Patients with earlier-stage disease may also benefit from neoadjuvant treatment in terms of improved rates of breast-conserving surgery and thus better quality of life. Gemcitabine is a pyrimidine analogue that has shown activity in a variety of solid tumors, a good toxicity profile, and nonoverlapping toxicity with other chemotherapeutic agents. Several phase II/III studies are assessing gemcitabine combined with anthracyclines, taxanes, and/or vinorelbine both in the neoadjuvant and metastatic disease settings. This article reviews developments in neoadjuvant use of gemcitabine in combination with anthracyclines and taxanes. Several phase II trials of gemcitabine combined with doxorubicin/epirubicin or with doxorubicin/paclitaxel have been carried out. Preliminary findings demonstrate increased complete response rates and good tolerability of these regimens in patients with breast cancer.
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PMID:Neoadjuvant gemcitabine therapy for breast cancer. 1205 45

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

Optimal therapy for pancreatic adenocarcinoma requires surgical removal with tumor-free margins. Superior outcomes have been reported for high-volume centers incorporating a multidisciplinary approach. Postoperative ("adjuvant") chemotherapy and radiation should be considered in patients with successfully resected primary tumors. Combined modality treatment with chemotherapy and radiation should be considered for locally advanced, unresectable tumors. Gemcitabine can provide symptom relief and a modest improvement in survival for patients with metastatic disease. Strict attention to relief of symptoms such as pain, depression, anorexia/cachexia, and jaundice is essential in all patients with pancreatic cancer. All patients with pancreatic cancer should be encouraged to enter clinical trials of new therapies, given that long-term survival for all stages remains poor.
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PMID:Pancreatic cancer. 1205 45


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