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)

From february 1988 to march 1989, 6 patients with locally advanced bladder cancer (T3b-T4, N0-N1, M0) were treated with 4 courses of neoadjuvant MP chemotherapy (methotrexate 300 mg/mq. + cisplatinum 100 mg/mq). In two patients chemotherapy was stopped because minimal or no response after two courses. Partial response (RP) was achieved in three patients (50%). Two patients died 2 and 5 month later. One patients developed metastases at 11 month. The remaining three cases showed NED at 3, 4 and 15 months of follow-up. In the same period 4 patients with metastatic bladder tumor were treated with M-VAC chemotherapy according to Yagoda before the cystectomy. M-VAC obtained a complete response in one case, and PR in 3 cases. All the metastases showed evidence of objective tumor regression. Reduction of bone pain was observed in one case. One patient died 15 months later with bone massive involvement. Another patient developed invasive tumor at 13 months. Two patients were disease-free at 3 and 5 months, respectively. Toxicity was more frequent in patient treated with M-VAC than with MP chemotherapy. M-VAC, we believe, represents a reliable neoadjuvant treatment of advanced metastatic bladder cancer.
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PMID:[Neoadjuvant chemotherapy of locally advanced tumors of the bladder: preliminary experience]. 214 8

Bladder cancer is largely a preventable disease; epidemiologic studies indicate that the majority of cases occur as a result of cigarette smoking or occupational exposures. The impact of screening high-risk populations is uncertain, but prompt and early diagnosis is essential for optimal therapeutic results. The management of different stages of disease varies greatly and is currently in a state of evolution. The majority of cancers are superficial, of low malignant potential, and can generally be treated cystoscopically. Few studies have addressed whether intravesical therapy will prevent high-risk patients with superficial disease from developing muscle invasion or distant metastases. Controversy exists as to optimal management of patients with invasive cancers. Improvements in technique and methodologies of urinary diversion have made cystectomy more tolerable for patients. Although cystectomy remains the "gold standard," probably not all patients require it. The careful selection of those patients whose bladders can be preserved is currently being evaluated. Combination chemotherapy for patients with metastatic bladder cancer is very active, appears to prolong survival, and may offer durable remissions to some patients. Whether chemotherapy will permit greater numbers of patients with invasive bladder cancer to be cured and bladders preserved remains to be determined.
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PMID:Bladder cancer. 222 21

In the present decade important progress has been made in the understanding of the biology and management of bladder cancer. Experimental laboratory models and new investigative tools have revealed potentially important prognostic markers and have led to an improved understanding of the histogenesis of the disease. Advances in the management of superficial bladder cancer (intravesical chemotherapy or immunotherapy, improved urinary cytology, laser technology, flexible fiberoptic cystoscopy, and photodynamic therapy) have, in some subgroups, improved tumor control while decreasing patient complications. For invasive bladder cancer (invasive of bladder muscle or beyond) improved techniques of cystectomy and radiotherapy have reduced the complications of treatment and may have contributed small but important improvements in cure. A major improvement in the last decade has occurred in objective remission rates with chemotherapy for patients with metastatic bladder cancer. From 20% to 40% of patients achieve a complete remission, and 10% to 20% may survive for more than 3 years. Randomized Phase III trials are currently in progress and must be completed to define the true role of multidrug chemotherapy in patients with metastatic disease and to validate data from the regimens of cyclophosphamide, methotrexate, and vincristine (CMV) and methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) before any of these approaches to treatment can be considered of proven benefit. Preliminary data from the Massachusetts General Hospital are presented of a potentially effective approach to select patients with invasive tumor for successful bladder preservation. In this approach transurethral debulking surgery is combined with upfront CMV chemotherapy plus cisplatin and 4000 cGy. If tumor is found on cystoscopic reevaluation with biopsy and cytology immediately following cisplatin and 4000 cGy, cystectomy is performed; if not, consolidation by a radiation boost to 6480 cGy plus cisplatin is given. The approach is fairly well tolerated, allows cystectomy without undue complications, has yielded a 88% complete response rate in patients selected for bladder preservation, and resulted in 90% of patients free of distant metastases with follow-up ranging from 6 to 30 months. A randomized Phase III trial with and without neoadjuvant MCV chemotherapy for selective bladder preservation is now under way and accruing well.
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PMID:Bladder cancer. Advances in laboratory innovations and clinical management, with emphasis on innovations allowing bladder-sparing approaches for patients with invasive tumors. 240 94

Progress has been made at both ends of the spectrum of bladder cancer. The introduction and increasing use of effective intravesical agents for both treatment and prophylaxis of tumors limited to the mucosa or lamina propria has reduced the incidence and frequency of subsequent tumors. At the other end of the spectrum--patients with locally extensive bladder cancer--neoadjuvant or initial chemotherapy is producing complete and partial responses. Hopefully this will translate into an improvement in the cure rate. In arriving at a decision regarding treatment for a patient with bladder cancer the urologist integrates information derived from a thorough endoscopic examination of the lower urinary tract (bladder and urethra), complete grading and staging of resected tumor including results of mucosal biopsies from suspicious and normal appearing urothelium, and cytology obtained by bladder irrigation. Treatment also may be influenced by such factors as prior history and treatment of bladder cancer and the patient's age and medical status. Assuming no prior bladder tumor history, endoscopic resection/fulguration followed by intravesical therapy will be used for tumors confined to the mucosa (Ta or Tcis) or lamina propria (TI). Optimally the urologist should resect all evident tumor and incorporate the intravesical agent as prophylaxis. Cytology and endoscopy will monitor the success of this approach. If the patient develops another superficial tumor while receiving prophylaxis another intravesical agent can be delivered, possibly using an intensive treatment schedule. Several agents have demonstrated effectiveness both for treatment and prophylaxis. They include mitomycin C, thiotepa, Adriamycin (doxorubicin), and bacillus Calmette-Guerin. The indications for radical cystectomy are invasion into the bladder muscle, tumor extension into the prostatic ducts or prostatic substance, or persistent tumor after an adequate trial of one or more intravesical agents used in conjunction with endoscopic resection. The escalating complete and partial response rates associated with combination chemotherapy of metastatic bladder cancer has led to the use of these regimens before considering cystectomy for patients with locally extensive bladder cancer, e.g., T3, T4, and N1-2. Downstaging with chemotherapy in this group of poor-risk patients may be preferable to the traditional approach of proceeding with exenterative surgery or full-dose radiation and considering chemotherapy later when metastases are evident.
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PMID:Selecting initial therapy for bladder cancer. 310 25

The goal of any treatment strategy for cancer is to improve not only patient survival but also quality of that survival. Quality of life (QL) involves individual perceptions (physical, mental, social) which are particularly germane to management of recurrent and advanced urologic cancers. Cancer therapy ideally equally documents a patient's QL as well as tumor response and survival. The QL is best achieved by optimal therapy, defined as appropriate treatment of those patients who need it and avoiding unnecessary or overtreatment of those patients who are not expected to obtain significant benefit. Specific goals of management of urologic neoplasms should strive to eradicate all existing and/or palliate symptomatic disease with the least possible morbidity while attempting to preserve function. Some examples of positive advances in this regard include reduction of therapeutic burden in good-risk patients with germ cell neoplasms; preservation of bladder and sexual function in childhood, adolescent and adult pelvic sarcomas with initial chemoradiotherapy programs and conservative surgery; improved responses of metastatic bladder cancer with combination chemotherapy; pelvic nerve-sparing techniques to preserve sexual potency and continent external or internal urinary diversions should total cystectomy become necessary; prevent or delay cystectomy with intravesical therapy in high-risk patients with polychronotopic superficial bladder tumors and ureteropyeloscopic management (rather than nephroureterectomy) of selected upper tract urothelial tumors. On the negative side, no appreciable value can yet be ascribed to nephrectomy, adjunct radiation or chemotherapy, hormonal or immunotherapy for advanced locoregional or metastatic renal cell carcinoma, aggressive radiation or chemotherapy for nodal metastases from bladder or prostate cancer or hormonal and/or chemotherapy of the asymptomatic patient with metastatic prostatic cancer. Future treatment strategies will improve tumor responses that now prove refractory but they should not be applied at the expense of QL as assessed by the patient. Valid methods for objective measurements of QL need to be devised and incorporated into multimodality curative and palliative clinical trials.
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PMID:Strategies for the management of recurrent and advanced urologic cancers. Quality of life. 329 89

Three chemotherapeutic agents, methotrexate, cyclophosphamide and cis-diamminedichloro-platinum (cis-platinum), were examined for their effectiveness against metastases in a murine transitional cell carcinoma model. Systemic treatment of the drugs was applied against a MBT-2 derived subline which generates 100% incidence of lung metastases in C3H mice by five weeks. The drugs were examined for their effect against the number of metastases, incidence of metastasis and size of the subcutaneously implanted primary tumor. All three compounds significantly reduced both the number of lung metastases and the incidence when compared to untreated animals. None of the agents proved 100% effective against metastatic tumors. These results suggest the existence of a chemotherapeutic resistant population of metastatic cells. Administration of methotrexate and cis-platinum effectively reduced the size of the primary tumor as compared to untreated animals. Cyclophosphamide did not significantly affect primary tumor size. The response of the antineoplastic agents against the metastatic tumor cells indicates that the L3F2 metastatic cell line is an effective model to study agents against metastatic bladder cancer.
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PMID:The efficacy of chemotherapeutic agents against murine bladder metastasis. 368 79

Combination three-drug chemotherapy with adriamycin (ADM), cyclophosphamide (CPM), and 5-fluorouracil (5-FU) was performed in 24 cases of advanced bladder cancer who underwent surgical treatment, and three cases with recurrent or metastatic bladder cancer. The average age (25 men and 2 women) was 53. Of the 24 cases, nine were in stage T2, 10 in T3, and five in T4. One course consisted of a combination of 30 mg/m2 of ADM, 300 mg/m2 of CPM, and, 250 mg of 5-FU, administered five times. The combination was administered to three groups: every day for 5 days consecutively in group A, twice a week for 21/2 weeks in group B, and once every 4 weeks for 16 weeks in group C. After injection of ADM, CPM, and 5-FU, 200 mg/day of 5-FU was administered PO daily in all three groups. The 5-year survival rate of the 24 cases (apart from 3 cases with measurable metastatic tumor) was 58%. The 5-year survival rate for stage T2 was 88%, and that for stage T3 was 62.5%; all patients with stage T4 disease died before 3 years and 6 months. Partial response was seen in two out of three patients with recurrent or metastatic disease. Alopecia was observed in all cases as a side-effect of the chemotherapy. Also anorexia, nausea, and myelosuppression were observed in many cases, though the degree was tolerable. However, there were no disorders of the cardiovascular system, except for one case with transient hypotension.
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PMID:Combination chemotherapy for advanced bladder cancer with adriamycin, cyclophosphamide, and 5-fluorouracil. 664 Aug 34

Over a period of 9 years (1970 to 1979), 64 patients with advanced local or metastatic bladder cancer were treated with methotrexate by one of three regimens. Response rates of 50% and over were noted with two of the three regimens studied. The response rate was greater for metastatic disease (44%) than for local disease (16%). Toxicity at the dosage used was minimal provided renal function was satisfactory.
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PMID:Methotrexate in advanced bladder cancer. 732 61

This review reports the results of chemotherapy in advanced bladder cancer with emphasis on the latest studies concerning combination chemotherapy containing cisplatin and methotrexate. The main conclusion is, that chemotherapy has a tumor-reducing effect on both metastatic disease and local/regional recurrences, but it remains to be proven whether overall long-term survival is affected. Among patients who respond to chemotherapy, the survival seems to be prolonged, 10-15% of these patients achieving more than two years of disease-free survival. The most effective treatment regimes contain cisplatin and methotrexate. It is assumed that many patients with muscle-invasive bladder tumors have microscopic dissemination of the disease at the time of diagnosis, and chemotherapy has been given to these patients as primary treatment alone or as an adjuvant to cystectomy or radiotherapy. These studies have not been able to show any benefit in terms of prolonged survival of patients receiving chemotherapy. The results of on-going randomised studies are still awaited. It is concluded that chemotherapy to patients with both primary and metastatic bladder cancer is still an experimental treatment, which should only be used in the context of investigational studies.
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PMID:[Systemic chemotherapy in bladder cancer]. 849 67

Overexpression of the TP53 gene protein detected by immunohistochemistry appears to identify those patients with superficial bladder cancer at risk of the development of muscle invasive or metastatic disease. However, the role of p53 overexpression in patients with advanced or metastatic bladder cancer is not yet well established. In the present study, 44 specimens from 44 patients with advanced stage bladder tumours (T2-T4) undergoing radical cystectomy were investigated for different biological and clinical characteristics as possible prognostic factors: sex, age, depth of tumour infiltration, T-stage, histological grade, lymph node status, application of adjuvant systemic chemotherapy (MVAC), proliferative activity (staining for proliferating cell nuclear antigen (PCNA) by monoclonal antibody (PC10) as well as overexpression of the p53 oncoprotein (monoclonal antibody pAb 1801)). After a median follow-up of 22 months, 16 of the 23 patients (70%) with more than 40% of tumour cells stained positively for p53 (Group B) died from tumour progression compared with 7 of the 21 patients (33%) with less than 40% of tumour cells positive for p53. During univariate analysis, p53 overexpression (P = 0.008), staining for PCNA (> or = 80% of cells positive) (P = 0.01) and tumour stage (P = 0.01) were significant prognostic factors for survival, among which p53 overexpression (P = 0.023) as well as T-stage (P = 0.012) remained independent significant predictors during multivariate analysis. Prospective studies are needed to confirm the independent prognostic potential of p53 overexpression in patients with advanced bladder cancer. The availability of more refined prognostic factors should assist decision making regarding the value of more aggressive treatment options, such as adjuvant or neoadjuvant chemotherapy, for prognostically defined subgroups of patients.
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PMID:p53 overexpression as a prognostic factor for advanced stage bladder cancer. 865 50


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