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 1996 two chemotherapy agents were introduced by the U.S. Food and Drug Administration (FDA) with indications for the gastrointestinal malignancies for advanced colon and pancreatic cancers. The agents approved were irinotecan hydrochloride (CAMPTOSAR Injection, Pharmacia & Upjohn Company, Kalamazoo, MI; also investigated under the name CPT-11) for the second-line treatment of metastatic colorectal cancer, recurrent or relapsed, after 5-fluorouracil (5-FU)-based therapy, and gemcitabine hydrochloride (GEMZAR for injection, Eli Lilly and Company, Indianapolis, IN; also referred to as dFdC) for first-line treatment of locally advanced and metastatic cancer of the pancreas. Irinotecan and gemcitabine, with demonstrated activity in colorectal and pancreatic cancer, respectively, are generally well tolerated and can be administered safely on an outpatient basis. Clinically relevant activity is documented for both single agents. Therapy-related side effects are manageable with appropriate monitoring and intervention, and reversible with dose modification or discontinuation. This article is one of a two-part series on new chemotherapeutic agents for gastrointestinal malignancies. The first in the series, this article addresses the agent irinotecan hydrochloride (CAMPTOSAR Injection). The second article, appearing in a subsequent issue, will review gemcitabine hydrochloride (Gemzar for Injection). Both articles review the current clinical use, safety profile, and key patient management guidelines for these new and novel cytotoxics. As clinical and investigational use of irinotecan and gemcitabine increases, the oncology nurse and other members of the health care team will need to anticipate potential treatment associated toxicities and be knowledgeable in their early identification and management. As patient advocates, oncology nurses play a key role in treatment outcome and related quality of life through expert patient education, symptom recognition, and intervention individualized to patient tolerance. This first article of the series addresses irinotecan, which in 1996 was approved for the second-line therapy of metastatic colorectal cancer, recurrent or elapsed, after 5-fluorouracil (5-FU).
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PMID:New agents in gastrointestinal malignancies: Part 1: Irinotecan in clinical practice. 1037 82

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

Because the majority of patients with stage IIIA N2 non-small-cell lung cancer (NSCLC) ultimately die of distant metastases, recent efforts to improve their intermediate- and long-term survival have focused on neoadjuvant chemotherapy (with or without radiotherapy) as an induction regimen followed by surgical resection. Over the last 15 years, more than 25 phase II trials and two small randomized phase III trials were terminated early because interim analyses confirmed the feasibility of the neoadjuvant approach and suggested a twofold increase in overall survival time compared to surgery alone. The gemcitabine (Gemzar)/cisplatin (Platinol) regimen proved effective in unresectable locally advanced and metastatic NSCLC. Consequently, it is logical to investigate the activity of this combination in locally advanced NSCLC. Preliminary results of five phase II trials have reported an average response rate > 60% in a mixed study population (IIIA and IIIB). Treatment is well tolerated. In studies using the 4-week schedule, the gemcitabine dose was frequently omitted on day 15, mainly due to thrombocytopenia. In January 2000, a randomized clinical trial (Chemotherapy for Early Stages Trial [ChEST]) was initiated in Italy to compare the efficacy of surgery alone vs surgery plus preoperative gemcitabine/cisplatin in early-stage disease (T2-3 N0, T1-2 N1, T3 N1) with the primary end point being progression-free survival.
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PMID:Gemcitabine/cisplatin as induction therapy for stage IIIA N2 non-small-cell lung cancer. 1096 Sep 40

This year, approximately 40% of the 28,300 patients diagnosed with pancreatic carcinoma in the United States will present with locally advanced disease. Radiotherapeutic approaches are often employed, as these patients have unresectable tumors by virtue of local invasion into the retroperitoneal vessels in the absence of clinically detectable metastases. These treatments include external-beam irradiation with and without fluorouracil (5-FU)-based chemotherapy, intraoperative irradiation, and more recently, external-beam irradiation with new systemic agents, such as gemcitabine (Gemzar).
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PMID:Current perspectives on locally advanced pancreatic cancer. 1112 40

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

Several trials have shown that anthracyclines and taxanes can be combined to achieve response rates ranging from 70% to 90%, with complete responses ranging from 19% to 41%. In an attempt to increase the activity while maintaining tolerability, gemcitabine (Gemzar) was added to the epirubicin (Ellence)/paclitaxel (Taxol) regimen. Among 36 metastatic breast cancer patients treated with this new combination, the overall response rate was 92%, including 31% with a complete response. Another attempt to improve the outcome of metastatic breast cancer patients involves a phase III multicentric randomized trial (MANTA-1) to evaluate if paclitaxel maintenance therapy after anthracycline/taxane combination therapy can improve time to progression and overall survival. Although anthracyclines are more frequently used in the adjuvant setting, it is important for the clinicians to know whether this class of drugs can be used again for those patients who develop metastatic disease. An analysis of 312 patients treated with epirubicin containing regimens as first-line treatment for metastatic disease shows that epirubicin-based regimens are active in patients already exposed to anthracyclines in the adjuvant setting, and that the risk of cardiac toxicity is low up to a cumulative epirubicin dose of 990 mg/m2.
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PMID:New combinations with epirubicin in advanced breast cancer. 1139 61

Invasive bladder cancer is a chemotherapy-sensitive neoplasm. Historically, the development of cisplatin (Platinol)-based chemotherapy regimens has represented an important advance for patients with metastatic disease. More recently, investigations of new agents, such as gemcitabine (Gemzar) and paclitaxel (Taxol), have resulted in further options for these patients. Randomized trials comparing new regimens with cisplatin-based therapies have been initiated. The role of chemotherapy in the adjuvant and neoadjuvant settings is an area that is undergoing active investigation. The application of prognostic biological markers to risk-stratify patients has resulted in new avenues of investigation in these ongoing early disease trials.
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PMID:Recent developments in chemotherapy for bladder cancer. 1143 Feb 8

This article will review the pertinent data on the use of chemotherapy for all stages of pancreatic cancer. For patients with metastatic disease, fluorouracil (5-FU) was the standard of care for several decades until a single randomized trial established that gemcitabine (Gemzar) produced a greater clinical benefit response, median survival, and 1-year survival. Among the currently available chemotherapy agents, the taxanes, fluoropyrimidines, and camptothecins are being evaluated in clinical trials alone or in combination with gemcitabine. Newer agents that are not classically cytotoxic are also under investigation and hold promise for the future. In patients with locally advanced unresectable disease, chemotherapy is commonly used to sensitize the cancer to radiation. Current investigations focus on trying to improve chemotherapy as a radiation sensitizer, using, for example, infusional 5-FU and gemcitabine. Early-stage, surgically resectable patients may benefit from the combination of chemotherapy and radiation, although more recent trials conducted in Europe raise some doubt. However, flaws in trial design do not allow firm conclusions to be drawn about the benefits of adjuvant therapy. Both chemotherapy and chemoradiation are under further investigation. Significant improvements in the survival of patients with pancreatic cancer will be achieved as more effective systemic therapies are developed, including agents with novel cellular targets.
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PMID:Chemotherapy for resectable and advanced pancreatic cancer. 1170 56

Improvements in surgical techniques, for example reconstructive surgery; and radiation therapy techniques, such as intensity-modulated radiotherapy; have made some impact on the functional outcomes of sarcomas with a local biology. Effective local control can be achieved with effective function in the vast majority of patients. The problem of distant metastases, however, continues to plague a large group of patients with this disease. Recent advances in the systemic therapy of sarcomas is highlighted by the rapid development and approval of the molecularly targeted therapy imatinib (Gleevec) for advanced gastrointestinal stromal tumors. Several other agents have been, or are being studied with far less rewarding results. Among these, the more encouraging examples include the nucleoside analog gemcitabine (Gemzar) and gemticibine/docetaxel (Taxotere) in combination, which display some selective activity in sarcomas of gynecologic origin. The marine compound ecteinascidin (ET-743) has been studied in two different schedules (24 and 3 h infusions), demonstrating biological activity worthy of further investigation. Identification of new agents with activity in this diverse group of diseases is extremely important. Identification of specific targets responsible for tumorigenesis and effective inhibition of these targets holds the most promise for future improvement in cure rates. However, until such time, it is equally important to emphasize clinical research attempting to further optimize the use of the standard chemotherapeutic agents, with growth-factor support in appropriately selected patients.
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PMID:Recent advances in systemic therapy of soft tissue sarcomas. 1272 77

Gemcitabine (Gemzar) and paclitaxel show good activity as single agents and combined in metastatic breast cancer, and the combination of paclitaxel/trastuzumab (Herceptin) has been shown to prolong time to disease progression and survival significantly in this setting. Preclinical data indicate additive or synergistic effects of gemcitabine and trastuzumab in HER2-positive human breast cancer cell lines. In a phase II trial, patients with HER2-overexpressing metastatic breast cancer who had received no prior chemotherapy for metastatic disease received gemcitabine at 1,200 mg/m2 on days 1 and 8 and paclitaxel at 175 mg/m2 on day 1 every 21 days for six cycles plus trastuzumab at an initial loading dose of 4 mg/kg followed by 2 mg/kg weekly; patients without progressive disease after six cycles continued to receive trastuzumab until disease progression. Overall, objective response was observed in 28 (67%) of 42 evaluable patients, including complete response in 4 (10%) and partial response in 24 (57%); stable disease was observed in 7 (17%) and progressive disease was observed in 6 (14%). Median time to treatment failure was 9+ months. Median overall survival has not yet been reached, but is estimated at approximately 27 months. Significant toxicities apart from neutropenia were uncommon. The triplet combination of gemcitabine, paclitaxel, and trastuzumab is highly active and well tolerated in patients with HER2-overexpressing metastatic breast cancer.
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PMID:Gemcitabine, paclitaxel, and trastuzumab in metastatic breast cancer. 1476 3


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