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)

Approximately 24,000 cases of renal cell carcinoma are expected in the United States in 1990. Although approximately 50% of patients with local disease are cured by surgery, in patients with metastatic disease the median survival is only approximately 10 months. Neither chemotherapy nor radiation therapy has been shown to be effective against metastatic renal cell carcinoma. Immunotherapy has come to the forefront of clinical research for the treatment of metastatic renal cell carcinoma. In the past decade, the development of recombinant DNA techniques has enabled the production of large quantities of biologic response modifiers such as the interferons and interleukins. Following initial reports in 1983 by the University of California-Los Angeles (UCLA) group and the investigators at M. D. Anderson Hospital, in Houston, TX, numerous trials have demonstrated a reproducible objective response rate to interferon of 15% to 20%. These responses are independent of the interferon preparation used, and optimal dosage/schedule has not been determined. In general, responses have been correlated with the following patient factors: previous nephrectomy, good performance status, a long disease-free interval, and lung-predominant disease. Median response durations of from 8 to 10 months can be expected. The addition of vinblastine, gamma-interferon, or aspirin has not improved the therapeutic index. Interleukin-2 therapy has produced encouraging results in 10% to 15% of patients. Although high-dose therapy is associated with substantive side effects, a small cohort of patients have been in continuous remission for extended periods of time, raising the possibility of "true" complete remissions of clinical significance. Recent trials, including our trials at UCLA, have combined the interleukins and interferons in this patient population. This combination has a sound scientific basis and the results are encouraging, especially when the toxicity profile is considered. Most patients receive these combinations as outpatients and have not required hospitalization nor suffered the toxicities of the high-dosage regimens. Complete pathologic remissions have been observed using this lower dosage, outpatient schedule. Clinical trials suggest that interferon and interleukin-2 may have an expanding role in metastatic kidney cancer both as single agents and in combination outpatient biologic therapy. The future clinical trials of kidney cancer will continue to incorporate these biologic response modifiers into the therapeutic strategies of the 1990s.
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PMID:The role of interferon and interleukin-2 in the immunotherapeutic approach to renal cell carcinoma. 171 41

We report the use of inhaled natural interleukin-2 in patients with metastatic disease. Six patients with metastatic renal cell carcinoma received 100,000 units natural interleukin-2, 5 times per day by inhalation in addition to a 4-day cycle of intravenous natural interleukin-2 every 2 weeks and subcutaneous interferon 5 days per week. Response was clearly correlated with metastatic site. Distinct tumor burden and the poor condition of the patient did not impair success. Pulmonary metastases responded in 5 of 5 patients. Metastases in the mediastinum, liver, abdomen and pelvis were stabilized in 4 patients. No response was noted in 3 solitary bone metastases, which were successfully removed surgically after several months of therapy, and a pleural metastasis progressed despite a clear response of the pulmonary disease in the same patient. New metastases did not develop in any of the patients during treatment (median followup 183 days of treatment, range 97 to 296 days). The over-all importance of the low toxicity of this novel route of administration (World Health Organization classification not exceeding grade 1) making long-term outpatient treatment possible must be emphasized because limitations of systemic interleukin-2 application are mainly caused by pulmonary side effects, for example pulmonary capillary leakage syndrome and edema. However, this new type of topical natural interleukin-2 application and combination with low dose intravenous interleukin-2 achieved considerable antitumor responses.
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PMID:Interleukin-2 by inhalation: local therapy for metastatic renal cell carcinoma. 173 90

Among 29 evaluable patients with progressive metastatic renal cell cancer treated by interferon alpha 2b in combination with vindesine and ifosfamide, we have observed an objective (complete and partial) response rate of 24.1% and an overall (complete and partial response and stable disease) response rate of 58.6%. The median duration of remission has not yet been reached, but the survival of responding patients is considerably longer than that of non-responders. Because we could not find any differences (sex, age, WHO performance status, prior therapy, site of metastatic disease) between responding and non-responding patients, we believe that the treatment might modify intrinsic characteristics of the tumour growth and/or host-tumour relationship in the long term. Although the toxicity recorded is high, the results are sufficiently positive to justify further investigation of this approach.
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PMID:Ifosfamide, vindesine and recombinant alpha-interferon combination chemotherapy for metastatic renal cell carcinoma. 179 11

A case of bilateral metachronous renal cell carcinoma with gallbladder and pancreatic metastases, presenting with hematobilia and anemia is presented. The presentation of metastatic renal cell carcinoma with hematobilia and anemia is previously unreported. This case illustrates (1) the occasionally very long interval between metachronous renal carcinoma; (2) this tumor's propensity to unusual metastases and unpredictable presentation; and (3) the significant palliation which may be achieved by appropriate surgical resection of these metastases.
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PMID:Gallbladder and pancreatic metastases from bilateral renal carcinoma presenting with hematobilia and anemia. 187 40

We report 4 cases of metastatic renal cell carcinoma (RCC) with long-term survival either following radical nephrectomy alone or in combination with radio- or hormonal therapy. Two patients with lymph node metastases showed a long-term survival of 12 or more years following radical tumour nephrectomy (with lymphadenectomy) and radiotherapy. One of them exhibited a histologically proven tumour recurrence nearly 12 years after primary surgical treatment and died shortly later; the other one is still without any evidence of metastatic disease. Two other patients exhibited spontaneous regression of pulmonary metastases: one regression occurred after radical tumour nephrectomy alone, the other one after successful primary hormonal treatment and subsequent radical tumour nephrectomy. The following important aspects are emphasized: 1. Renal cell carcinoma is a very unpredictable tumour. Once the diagnosis of renal cell carcinoma is proved, a patient can never be considered cured. 2. Although adjuvant palliative nephrectomy has produced contradictory results in several reports, radical tumour nephrectomy either alone or in combination with other adjuvant therapies such as radiotherapy, hormonal or immunological treatment, can be worthwhile. Cases with long-term survival and spontaneous regression of distant metastases are proof of this. Besides, if carefully selected, the mortality rate of different adjuvant therapies is not significantly higher in patients with metastatic disease than in patients without metastases. The world literature on this subject is reviewed.
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PMID:Metastatic renal cell carcinoma (RCC): spontaneous regression, long-term survival and late recurrence. 193 15

We reviewed 57 cases of Stage IV renal cell carcinoma to clarify the factors influencing prognosis and to evaluate the value of nephrectomy. Cumulative survival from the initial diagnosis was analyzed with respect to the patients' age, sex, side of primary tumor, initial performance status (PS), site of metastasis, and nephrectomy. Overall survival for the patients was 51 percent at one year, 22 percent at three years, and 11 percent at five years. Age, sex, and side of primary tumor had no influence on survival. Improved survival was correlated with good PS, metastases limited to single organ, and removal of the primary tumor. With regard to histopathologic features in nephrectomized patients, low grade and stage were correlated with longer survival. These factors should be considered in the analysis of results of future clinical trials of metastatic renal cell carcinoma.
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PMID:Prognostic factors and value of adjunctive nephrectomy in patients with stage IV renal cell carcinoma. 199 96

We administered 10 (E5) units per kg. interleukin-2, 3 times daily, with or without lymphokine-activated killer cells, to 10 patients with metastatic renal cell carcinoma. All patients had metastases to the lung, and 3 of 5 patients who had previously undergone nephrectomy had metastases to the renal fossa. Of the 9 patients who completed at least 1 course of therapy 3 had complete regression of disease outside the abdomen, including 2 who were rendered disease-free after subsequent cytoreductive surgery (nephrectomy in 1 and resection of the renal fossa recurrence in 1). Viable tumor comprised less than 1% of each surgical specimen. Our results support the view that initial treatment with interleukin-2 immunotherapy, followed by abdominal cytoreductive surgery if the peripheral metastases have regressed, may be preferable to the practice of performing abdominal cytoreductive surgery before administering interleukin-2 immunotherapy for patients with widely metastatic renal cell carcinoma.
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PMID:Interleukin-2 immunotherapy followed by resection of residual renal cell carcinoma. 201 5

Sixty patients with metastatic renal cell carcinoma were entered into an ongoing randomized phase II study with lonidamine, 350 mg/m2 orally daily (arm A) and high dose tamoxifen, 150 mg/m2 orally daily for 6 months, afterwards 50 mg/m2 (arm B), until tumor progression. All patients had measurable disease and documented tumor progression prior to treatment. There were 1 complete and 1 partial remission among 19 evaluable patients in arm A (10.5%) and 2 complete and 1 partial remission among 25 evaluable patients (12%) in arm B. Objective responses were observed in pulmonary, nodal, and cutaneous metastases. In addition, in 63% and 64% tumor progression could be stopped in arm A and B, respectively. Median response duration was 100 days (range, 20-361) in arm A and 150 days (range, 28-355) in arm B. One year survival rate was 37.5% with lonidamine and 35% with tamoxifen. In arm A patients with tumor progression within 12 weeks after diagnosis of metastatic disease survived significantly shorter than patients with a longer interval (P less than 0.05). Nephrectomy or number and localization of metastatic sites failed to significantly influence probability of remission or survival. Toxicity was mostly mild to moderate. Four patients in the lonidamine arm had to discontinue treatment because of intolerable myalgias, which were immediately reversible. These data suggest that lonidamine and high-dose tamoxifen are moderately effective in widespread renal cell carcinoma where treatment intention is palliative.
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PMID:Lonidamine versus high-dose tamoxifen in progressive, advanced renal cell carcinoma: results of an ongoing randomized phase II study. 203 Nov 96

Human lymphoblastoid interferon-alpha was administered intramuscularly at a dose of 5 x 10(6) units/day to 20 metastatic renal cell carcinoma patients. For potentiating the antitumor effect of interferon, cimetidine was also given to them orally at a dose of 800 mg/day. The combination therapy obtained a complete response in three patients (15%) and a partial response in three (15%). Nine patients (45%) had stable disease and five (25%), progressive disease. All six patients who responded to the combination therapy had been nephrectomized and had pulmonary metastases. Two of them also had metastases to other sites (mediastinal lymph nodes and bone). The pulmonary metastases were significantly more receptive to interferon therapy than those at the other sites. The average times before a response was obtained were 2.2 months for a minor response, 2.7 months for a partial response and 3.0 months for a complete response, and the average duration of response was 26 months. The six patients who responded survived for a significantly longer period than the 14 non-responding patients treated with interferon in combination with cimetidine. The major toxicities encountered were fever, fatigue and anorexia due to interferon, and the combination therapy was well tolerated except in three patients. The results suggest that interferon-alpha and cimetidine combination therapy may be of use in the management of patients with metastatic renal cell carcinoma.
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PMID:Treatment of metastatic renal cell carcinoma with a combination of human lymphoblastoid interferon-alpha and cimetidine. 206 20

Fourteen patients with metastatic renal cell carcinoma (RCC) were treated by systemic administration of autologous lymphokine-activated killer (LAK) cells and interleukin-2 (IL-2). Pulmonary metastases alone were found in 9 cases, pulmonary and mediastinal nodal metastases in 3, and pulmonary and bone metastases in 2. LAK cells, generated by incubation in 2 units/ml of IL 2 for 3-4 days, were intravenously administered once or twice a week. In addition, beginning on the day of the first LAK cell infusion, 1000 units of IL 2 diluted in normal saline were intravenously infused once or twice a day with occasional supplementation of 1000 units of IL-2 on each day of LAK cell infusion. The total number of LAK cells and total amount of IL-2 administered per patient in this study ranged from 0.8 x 10(10) to 6.9 x 10(10) cells and from 3.3 x 10(4) to 21.4 x 10(4) units, respectively. As toxic effects caused by the infusion of LAK cells, headache, shaking chills, fever and leukocytosis were found in all 14 cases. Side effects possibly induced by IL-2 infusion were tolerable fever, fluid retention (body weight gain of 2-3 kg) and eosinophilia. No objective regression of mediastinal nodal or bone metastases was observed. In regard to lung metastases, however, partial and minor responses were observed in 3 and 2 cases, respectively. One of the 3 patients with a partial response was clinically free of disease after undergoing a thoracotomy for resection of residual lesions, but a brain metastasis was detected 10 months after the thoracotomy. The remaining 2 patients are being closely followed up at present. In 3 of 11 patients who showed a minor response, no change or progressive disease, brain metastases were observed during or after the immunotherapy. Furthermore, we examined the possibility of selection of suitable candidates for this therapy on the basis of the degree of in vitro LAK activity against autologous cultured tumor cells in 6 patients, but there was no significant correlation between in vitro autologous tumor cell lysis by LAK cells and the clinical response to immunotherapy. In conclusion, although a complete response could not be obtained, it can be said that this immunotherapy may be effective against RCC, in particular lung metastases, since a partial response was achieved in 3 of 14 patients. However, it should be taken into consideration that this immunotherapeutic approach may have a risk of increasing the frequency of brain metastases.
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PMID:[Usefulness and limitation of immunotherapy of metastatic renal cell carcinoma with autologous lymphokine-activated killer cells and interleukin 2]. 207 2


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