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)

All of the third-generation chemotherapeutic agents reviewed in this article are independently active against NSCLC, although the agents differ significantly in their cellular and molecular mechanisms of cytotoxicity. All have also been shown to potentiate radiation effects, and thus are promising in exerting further cytotoxicity when used in combination chemoradiation therapy for locally advanced NSCLC. Although the toxicity to normal tissue varies among these agents when used alone, phase I/II clinical results consistently demonstrated higher risk and severity of esophagitis and pneumonitis when these agents were administered concurrently with thoracic radiation. These results were consistent with the radiosensitization properties of all these agents. Nonetheless, most chemoradiation combinations have been made feasible through careful phase I studies that establish safe doses of these agents given concurrently with radiation. Indeed, phase I outcomes consistently have demonstrated the need for dose reduction compared with doses applied in the stage IV, metastatic disease setting (see Tables 1 and 2). There have been many different dose schedules in phase I/II studies for stage III NSCLC, and most have yielded improved response rates with these agents. For all these agents discussed, multiagent chemoradiation increased toxicity when compared with single agent chemoradiation, particularly in the risk of neutropenia, and the tumor response rates were no better than single-agent chemoradiation. Most studies have not reached an adequate interval for survival endpoint to assess the impact on survival using multiagent chemoradiation. A few earlier studies using paclitaxel chemoradiation, in fact, showed that the significant improvement in tumor response rate resulted in only a small gain in survival outcome. Despite much preclinical research conducted with these agents, the optimal sequence and dose of drug and the optimal schedule for combining the two modalities remain unknown. Optimal sequencing of the chemoradiation regimens may improve distant disease control and primary tumor control, as was seen in studies that administered both full-dose induction chemotherapy and concurrent chemoradiation at reduced drug dose and in studies that administered consolidative, full-dose chemotherapy after chemoradiation. Strategically altering the treatment schedule may also enhance the radiosensitizing effects while keeping toxicity low, such as was seen in the pulsed low-dose paclitaxel chemoradiation reported by Chen et al . This pulsed low-dose schedule resulted in superior tumor response (100%) and durable primary tumor control while keeping the toxicity low. Other methods to minimize normal tissue injury and to deliver higher radiation doses, such as conformal three-dimensional radiotherapy that excludes nontarget tissues from the radiation field, are under investigation. Marks and colleagues were able to deliver radiation to 80 Gy using accelerated hyperfractionation radiation after induction chemotherapy. Intensity-modulated radiotherapy is expected to revolutionize the targeting of tumor and exclusion of normal tissues from the high-dose radiation volume in the future. Integrating biologic response modifiers, radioprotectors, and molecular targeting strategies also are being investigated. It remains unclear which agent among the third-generation drugs performs better for combination chemoradiation. The CALGB 9431 study reported by Vokes et al provided some preliminary information, in that it was a randomized phase II study of a three-arm comparison of cisplatin-containing, two-drug combination chemoradiation with one of the third-generation agents. Although direct statistical comparison between the treatment arms was not valid for a phase II setting, such an analysis did indeed reveal similar overall response rates for these three arms. Chemoradiation using third-generation chemotherapeutic agents has improved local tumor response rates, with enhanced radiation toxicity such as esophagitis and pneumonitis. The challenge of targeting distant disease control for locally advanced NSCLC continues.
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PMID:Radiation and third-generation chemotherapy. 1500 81

The preceding platinum-based combination chemotherapy could possibly reduce tumor masses, allowing for adequate surgical debulking in advanced ovarian cancer. In this study, a total of 18 patients with peritoneal carcinomatosis of the ovary were evaluated between 1996 and 2003. All patients underwent open biopsy for the histopathologic confirmation of ovarian tumor. Forty-one percent of the patients (8/18) were administered six cycles of carboplatin/cyclophosphamide (CP) and the rest were administered six cycles of paclitaxel/carboplatin (TP) as a neoadjuvant chemotherapy (10/18). After six cycles of chemotherapy metastases to the peritoneum, Douglas' pouch, diaphragm, and liver serosa were higher in the CP group than the TP group (p < 0.05). All patients also had a better performance status (WHO performance status 0 or 1), but no statistical difference was observed between either group (p > 0.05). Optimal debulking surgery rates were significantly higher in the TP group (p < 0.05). In conclusion, we suggest paclitaxel/carboplatin in peritoneal carcinomatosis of the ovary as a neoadjuvant chemotherapy. However, large prospective, randomized studies should be performed in patients with peritoneal carcinomatosis of the ovary.
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PMID:Paclitaxel/carboplatin versus cyclophosphamide/carboplatin in peritoneal carcinomatosis of the ovary. 1503 80

Approximately 11,000 new cases of connective tissue malignancies are anticipated in 2004. These diseases can be divided into soft-tissue sarcomas, sarcomas of bone, and gastrointestinal stromal tumors. Optimal management of these diseases requires a multidisciplinary team with expertise in surgery, pathology, radiotherapy, and chemotherapy. Over half of patients with stage III soft tissue and bone sarcomas are cured, as are some patients with metastatic disease. Imatinib mesylate has been an important advance in the treatment of gastrointestinal stromal tumors.
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PMID:Update on the management of connective tissue malignancies. 1512 29

Malignancy-related thromboembolism, so-called Trousseau's syndrome, can present as acute cerebral infarction, non-bacterial thrombotic endocarditis (NBTE) and migratory thrombophlebitis. It is usually attributed to a cancer-related hypercoagulable state, chronic disseminated intravascular coagulopathy (DIC), or tumour embolism. We report on two patients with adenocarcinoma of the colon and cholangiocarcinoma who developed widespread thromboembolism during disease progression. Both did poorly despite aggressive institution of anticoagulation therapy. These cases emphasize that cerebral infarction or refractory thromboembolism in cancer-treated patients should prompt investigation for recurrent or metastatic disease or progression of the underlying malignancy. Optimal treatment remains to be established.
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PMID:Trousseau's syndrome related to adenocarcinoma of the colon and cholangiocarcinoma. 1525 90

The extracellular polysaccharide hyaluronan (HA) controls cell migration, differentiation and proliferation, and contributes to the invasiveness of human cancers. The roles of HA cell surface receptors and hyaluronidases (HAses) in this process are still controversial. In order to investigate their involvement in cancer pathogenesis, we developed a reticulated HA hydrogel, a three-dimensional matrix in which cells can invade and grow. We have studied thirteen cell lines, from primary tumors or metastases, that migrated into the HA hydrogel and proliferated giving rise to clusters and colonies. The number of colonies, which reflects tumor cell invasiveness, ranged from 7 to 193 after 5 days of culture. Invasion was dependent on the production of HAse as well as other factors. Optimal colonization occurred when cells released HAse, lacked HA-binding sites and did not secrete HA. Moreover, we describe for the first time a HAse activity at physiological pH that may be responding to the confinement of the enzyme in a three-dimensional structure. We show here that this reticulated matrix provides a three-dimensional model for investigating mechanisms involved in malignant invasion.
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PMID:Reticulated hyaluronan hydrogels: a model for examining cancer cell invasion in 3D. 1529 46

Intramedullary spinal cord metastases (ISCMs) are extremely rare. An exact diagnosis may be difficult even when the primary tumour is known. Patients usually present with back pain and signs and symptoms of spinal cord compression, such as hemiparesis or hemisensory impairments. Magnetic resonance imaging (MRI) is considered to be the main diagnostic tool for intramedullary lesions as it is very sensitive, but non-specific, in distinguishing between ISCMs and primary cord tumours. Optimal treatment in patients with ISCMs remains controversial. We report a case of ISCMs of melanoma, with a review of the clinical and radiological characteristics of these medullary lesions and their prognosis, as well as the different therapeutic approaches.
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PMID:Intramedullary spinal cord metastases of melanoma. 1545 3

Optimal extent of surgery for lung cancer is determined to a great degree by lymph drainage and regional metastases vis-a-vis tumor localization in the lobes. Data on surgical treatment of 505 cases of cancer of the lower lobe are presented. The study established such peculiarities of metastatic spread to mediastinal lymph collector as relatively frequent involvement of the lower mediastinal lymph nodes ("jumping" metastases included) and greater likelihood of spread to the superior mediastinal lymph nodes when those of radix pulmonis are involved. The latter should be interpreted as an indicator of lower lobe involvement. We established the significance of relatively worse prognosis for mediastinal lymph node involvement as well as high frequency of intrasternal recurrences of tumors located in the left lung. The prevailing evidence on partial resections of the right lung rather than lower bilobectomy and the good results of bilobectomies for stage T1-3N1-2 tumors suggest that conservative treatment might offer more advantage in managing cancer of the lower lobe of the right lung. Extended surgery entails lower incidence of intrasternal recurrence and is more effective when used to treat right-lung tumors.
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PMID:[Rationale for surgical treatment of cancer of the lower pulmonary lobe with consideration for regional metastatic spread]. 1575 68

Brain metastases are ten-times more common than primary brain tumors and are a common complication in patients with systemic cancer. The most common sources of brain metastases are lung and breast cancers, although in 15% of patients, the primary site is unknown. Optimal treatment is dependant upon tumor location, size, number of tumors and status of the systemic disease. Currently, management of brain metastases with surgery, radiotherapy and stereotactic radiosurgery is known to improve the quality of life and even life expectancy for selected patients. Techniques under investigation include focal radiation techniques, magnetic resonance imaging guided thermal ablation of metastases, drug delivery modes that bypass the blood-brain barrier and novel drug and molecular therapeutics. Efforts are ongoing to understand the molecular biology of brain metastases.
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PMID:Metastases to the brain: current management perspectives. 1585 82

Patients with primary brain tumors and those with cerebral metastases are at risk throughout their illness for several major medical problems, including vasogenic edema, seizures, and symptomatic venous thrombosis. In turn, the corticosteroids, anti-epileptic drugs, and anticoagulants used to treat these problems may produce significant adverse effects and result in important drug-drug interactions that may complicate chemotherapy. Although few Class I studies address any of these issues, guidelines can be offered to maximize quality of life and minimize hospital readmissions. Optimal management of brain edema involves minimizing corticosteroid use and tapering the steroid dose slowly to avoid steroid withdrawal symptoms. Prophylaxis of Pneumocystis pneumonia is necessary for patients requiring corticosteroids for more than 1 month. Anti-epileptic drugs (AEDs) should be avoided unless patients experience seizures. If possible, non-CTY (P450) enzyme-inducing drugs should be chosen. AED levels should be obtained frequently during corticosteroid taper. Multimodality venous thrombosis prophylaxis should begin at the time of the original surgery with external leg compression and unfractionated subcutaneous heparin or a low molecular weight heparin (LMWH). Brain tumor patients with symptomatic venous thrombosis or pulmonary embolism can be anticoagulated safely with warfarin or with LMWH, and LMWHs are preferable from the standpoints of efficacy, safety, and convenience for long-term outpatient treatment of venous thrombosis. Clinicians should be aware of potential drug-drug interactions between prescribed AEDs and chemotherapy and possible interactions with complementary and alternative therapies chosen by their patients. They also should be aware of interventions to minimize late sequelae of brain tumors and their treatment, including cognitive decline, depression, and increased stroke risk.
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PMID:Treatment of Medical Complications in Patients with Brain Tumors. 1596 95

The management of stage IV epithelial ovarian carcinoma remains controversial. The aim of this study was to evaluate and compare our results to other published series. A retrospective database and casenote review was performed on all patients diagnosed with stage IV disease over a ten-year period (1992-2002). Survival analysis was performed using the Kaplan-Meier and Mantel-Haenszel methods. The study group comprised 23 women. Nine had positive pleural effusions (39.1%), and 14 had other sites of metastases (60.9%). Nine patients underwent interval debulking (39.1%), and 14 were operated on primarily (60.9%). We had six postoperative complications (26.1%) but no perioperative deaths. Optimal cytoreduction (inferior or equal to 2 cm residual disease) was obtained in 18 patients (78.3%). The overall median survival was 22.6 months. There was no statistically significant difference in overall or disease-free survival between primary surgery and interval debulking. Patients with positive pleural effusions had significantly reduced survival compared to those with distant metastases in other sites. Interestingly, there was no difference in survival between optimally and suboptimally cytoreduced patients. Debulking surgery can be performed in patients with stage IV ovarian cancer, with an acceptable level of morbidity. Optimal cytoreduction is achievable in the majority of these patients. Interval debulking should be considered in selected patients.
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PMID:Stage IV ovarian cancer: a retrospective study on patient's management and outcome in a single institution. 1601 13


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