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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

At present, no sufficient therapy for metastatic renal cell carcinoma is available. Several immunotherapeutical protocols have been studied, success rates, however, were inconsistent. The purpose of this study was to assess the pretherapeutic immunological status of 13 patients with metastatic and 16 patients with nonmetastatic renal cell carcinoma and of 15 healthy volunteers. Determined were differential blood counts, lymphocyte subpopulations, beta 2-microglobulin, tumor necrosis factor (TNF), neopterin, immunoglobulin, fibronectin and ferritin. Additionally, these parameters were recorded for monitoring an immunotherapeutical approach with the xenogeneic biological response modifier Keyhole limpet hemocyanine (KLH) in 10 patients with metastatic and in 5 patients with nonmetastatic disease. The pretherapeutic immunological status of patients with metastatic disease was characterized by significantly reduced T4-, T8- and B-cell counts. Significantly increased were granulocyte counts, beta 2-microglobulin, neopterin and TNF. In patients who did not suffer from metastases, only beta 2-microglobulin and neopterin were increased significantly. During immunotherapy, in patients with metastases, there was a decline of lymphocyte subsets and of the T4/T8-ratio, which correlated with progress of the disease. Humoral immune parameters showed no changes compared to pretherapeutic values. In patients who did not suffer from metastases, cellular immune parameters showed stable values during immunotherapy; neopterin, beta 2-microglobulin and TNF increased considerably. These findings indicate immunosuppression in patients with metastatic renal cell carcinoma, increasing with progression of the disease and possibly impairing the immunostimulating effects of biological response modifiers during immunotherapy. In conclusion, the clinical response of metastatic renal cell carcinoma to immunotherapy might be improved if the immunostimulant is combined with agents suitable to overcome immunosuppression, i.e. low doses of cyclophosphamide or inhibitors of prostaglandin synthesis. In addition, assessment of immune parameters for monitoring the actual immune status of a patient and the immunological effects of therapy was found to be a necessary part of immunotherapy.
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PMID:Immune status and immune therapy of renal cell carcinoma. 221 64

Recombinant interferon alpha-C is a new strain of the alpha interferon family. It was given to 33 patients with measurable metastatic renal cell carcinoma of whom 31 were evaluable. Protocol consisted of 3 million U/d for 2 weeks, then 3 million U/m2 every other day until progression. No complete response was observed. Three patients (9.7%) had partial response for a mean duration of 5.6 months and eight patients (25.8%) were stabilized for a mean of 4.3 months. Responsive sites were mainly lung, bone, and kidney, while side effects were generally mild. better results were observed in previously nephrectomized patients who had not received chemotherapy or hormonotherapy for recurrent or metastatic disease (p less than 0.05), and also in patients with a brief disease-free interval and short delay from presenting symptoms of the primary tumor until interferon treatment (p less than 0.05). Median survival was significantly longer in responders than in progressors (p less than 0.05). We suggest that the efficacy of recombinant interferon alpha-C in a low-dose regime versus other types of interferon as first-line therapy for inoperable, metastatic, or locally recurrent renal cell carcinoma should be investigated in a prospective, controlled, randomized study.
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PMID:Phase II study of recombinant interferon alpha-C in patients with metastatic renal cell carcinoma. 222 99

Interferon-beta-serine (IFN-beta-ser) is a muteine, recombinant IFN that is tolerated at a dose fivefold to 10-fold higher than IFN-alfa and interacts with the same cell membrane receptor as IFN-alfa. We hypothesized that at high doses IFN-beta-ser might induce a higher response rate than IFN-alfa in metastatic renal cell carcinoma. We undertook a phase II trial of IFN-beta-ser in patients with metastatic renal cell carcinoma. Patients were treated three times each week by a 2-hour intravenous infusion. Doses were escalated weekly (.25 to 5.5 mg, 1 mg = 180,000,000 U) until the maximum-tolerated treatment dose (MTTD) was determined. The MTTD is defined as one dose level less than that which caused grade 3 toxicity and was subsequently administered three times weekly for at least 4 weeks. Twenty-nine patients were entered, and 25 were assessable for response and toxicity. The performance status was 0-1 in all patients and only one patient received previous chemotherapy. The MTTD dose was 2.5 mg (range, 0.5 to 5.5 mg per treatment), although in 10 patients, doses were later deescalated because of cumulative toxicity. Initial dose-limiting toxicity and cumulative toxicity were fatigue, malaise, and fever in most patients. Hepatic transaminitis, neutropenia, and elevation of serum creatinine were also observed but were not dose-limiting. There was one complete response (CR) and four partial responses (PRs). All responses but one occurred in pulmonary metastases. The median time to response was 26 days (range, 17 to 102 days). These data demonstrate that IFN-beta-ser given in high doses exhibits significant antitumor activity in renal cell carcinoma; however, the objective response rate is 20%. This is no higher than previous IFN studies; therefore, we reject the hypothesis than IFN-beta-ser at high doses may induce a greater response rate than IFN-alfa. However, we did observe more responses than were seen in a similar trial undertaken with lower dose IFN-beta serine in renal cell carcinoma.
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PMID:Phase II trial of interferon-beta-serine in metastatic renal cell carcinoma. 233 72

Five responses (lung metastases, three; lymph node metastases, two) were observed in 23 patients with metastatic renal cell carcinoma who received recombinant interferon-alpha-2A (IFN) 18 X 10(6) U in three intramuscular doses each week combined with oral prednisone (10 to 20 mg daily). The response duration was 4+, 4+, 9, 11+, and 15+ months. In general, the combination treatment of interferon and prednisone lead to a significant reduction of the subjective side effects (flu-like symptoms) as compared to a previous experience in patients treated with interferon only. Reduction of the interferon dose or discontinuation of IFN treatment was necessary in only two of 23 patients receiving IFN plus prednisone. Prednisone, however, had little effect on the hepatic toxicity often associated with high-dose IFN treatment. The subjective tolerability of a high dose of IFN is significantly increased if oral prednisone (10-20 mg) is given concomitantly in patients with metastatic renal cell carcinoma without reducing the response rate. Randomized trials will be necessary to confirm the efficacy of the IFN and prednisone combination. In addition, higher doses of IFN combined with prednisone should be evaluated in this malignancy.
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PMID:Recombinant interferon-alpha combined with prednisone in metastatic renal cell carcinoma. Reduced toxicity without reduction of the response rate--a phase II study. 233 59

Clinically localized renal cell carcinoma is cured by radical nephrectomy in 47% [stage T3a (II)] to 65% [stage T1, T2 (I)] of the patients. Local recurrence and metastatic disease probably result from undetectable microscopic metastases present at operation. Chemotherapy and immunotherapy may improve cure rates if administered adjuvantly. The outcome of individual patients who share surgical stage cannot be predicted reliably by tumor histology, pathological and/or nuclear deoxyribonucleic acid analysis. Two groups of 10 patients with clinically localized renal cell carcinoma were similar by sex distribution (5 men and 5 women), surgical stage (stages T1 in 1, T2 in 6 and T3a in 3 patients) and age (54.3 +/- 15.2 standard deviation versus 55.8 +/- 8.7 years). Group 1 had no recurrences with a minimum followup of 5 years and a mean followup of 10 years. Group 2 died of metastatic renal cell carcinoma after a mean of 5 years. All neoplastic areas of each paraffin-embedded operative specimen were randomly sampled and the nuclear perimeter of 150 cancerous cells was digitized. There were 25 shape descriptors calculated for each nucleus. All shape descriptors for each patient were described by 19 statistical tests. Nuclear perimeter and area as well as mean nuclear roundness factor failed to separate the 2 groups. Range median quartiles of ellipticities by Fourier analysis, coefficients of variation of chain code minimums and relative means of largest 10 convexity values produced greatest separation (Mann-Whitney-Wilcoxon test p less than 0.001, and variance normalized difference 3.21, 3.29 and 2.83, respectively). These descriptors normalized and summed provided near perfect separation (Mann-Whitney-Wilcoxon test p less than 0.001 and variance normalized difference 3.59). We developed a quantitative nuclear morphometric analysis system that permitted the correct assignment of outcome in 19 of 20 patients. Accurate prediction of prognosis in patients with clinically localized renal cell carcinoma by nuclear shape analysis may allow for selection of patients for adjuvant therapy who have clinically undetectable metastatic disease.
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PMID:Nuclear shape analysis for assessment of prognosis in renal cell carcinoma. 234 68

Clinical, histopathological and DNA cytometric parameters were analyzed before treatment in 57 patients with metastatic renal cell carcinoma (RCC) with regard to their ability to predict objective response to treatment with interferon-alpha (IFN) with or without vinblastine (VB). No pretreatment factor could be identified which was correlated with response. Patients who had at least 30% size reduction of their indicator lesion(s) after 2 months and did not present with new visible metastases had a significantly higher chance to obtain objective response than those in whom this condition was not fulfilled. We suggest that interferon treatment (with or without VB) should be offered for 2 months to all patients with metastatic RCC who are to receive systemic therapy. If at least 30% tumour size reduction is observed at that time, the patient will most probably respond objectively. If the size reduction is less, IFN with or without VB is likely to be ineffective in terms of response achievement.
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PMID:Prediction of objective response to recombinant interferon-alpha with or without vinblastine in metastatic renal cell carcinoma. 236 42

A report is presented on 78 patients with metastatic renal cell carcinoma (RCC, Robson III and IV). The average survival time was 2.1 years after nephrectomy, 1.1 years after embolization and only 0.65 years in the patients who underwent no surgery at all. As there is still not known effective systemic cytostatic therapy for this type of tumour, there is no doubt about the priority of nephrectomy. The indication for nephrectomy is limited by the feasibility of total removal of the metastases. An extension of this indication limit has not improved the survival rate. There is no difference in survival rate between patients with removable local, as opposed to operable distant metastases. In those cases where nephrectomy was not possible the patients did better after embolization than with no surgery at all.
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PMID:[Status of surgery in the treatment of metastatic renal cell carcinoma]. 244 67

Despite the prevalent scepticism regarding its value, chemotherapy for metastatic renal cell cancer was used in 45 patients, of whom 44 were nephrectomized, aged between 34 and 75 yr with a mean age of 57.3 yr. In 32 patients chemotherapy was used as palliative treatment because of the presence of their often multiple metastases or in 13 patients following surgical removal of metastases and/or histologically high-grade malignancy, as adjuvant treatment. Our treatment schedule consisted on day 1 of vinblastine 5 mg/m2 to a maximum of 10 mg provided intravenously in 1 or 2 to 3 week intervals X 6 and CCNU 130 mg/m2 orally each 6th week. This treatment schedule was supported by an intensive antiemetic regimen. Gastrointestinal side effects were well tolerated while 30% hematological depression necessitated extension of treatment intervals. The mean number of cycles was 2.5-3.7, respectively, with a maximum of 6. Palliative treatment resulted in 19% complete plus partial remission, 62% stabilization, and 19% progression, while adjuvant therapy proved to be superior with 10 of 13 patients in remission at 3-21 months, and 1 of 3 patients with metastatic recurrence in further remission for 20 months; two of three patients died. Palliative chemotherapy with CCNU-vinblastine acted successfully by blocking cancer progression, while adjuvant treatment together with surgical extirpation of metastases may have prolonged tumor-free remission.
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PMID:Palliative and adjuvant chemotherapy of metastatic renal cancer. 245 28

The management of renal cell carcinoma remains a therapeutic challenge. For patients with localized disease, surgery represents the only curative treatment modality. Neither postoperative radiotherapy nor systemic hormonal therapy is of additional benefit in this setting. There are ongoing studies evaluating the role of biologic response modifiers, such as interferon and interleukin-2, as adjuncts to surgery. Patients with recurrent or metastatic disease have a poor prognosis and are a natural target for clinical trials designed to evaluate potential therapeutic modalities. Cytotoxic drugs and hormonal therapies are usually ineffective. The advent of interferon, and more recently of interleukin-2, has resulted in a modest advance in therapy of metastatic renal cell carcinoma. Studies designed to evaluate mechanisms associated with intrinsic or acquired resistance to cytotoxic drugs, as well as to biologic response modifiers, will lead to a better understanding of the biology of the disease and, ultimately, to a more rational and effective use of various therapeutic agents.
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PMID:Therapeutic options in renal cell carcinoma. 246 74

High dose medroxyprogesterone treatment was given to 20 patients with metastatic renal cell carcinoma. Distant metastases occurred before the perifascial nephrectomy in 11 patients and following nephrectomy in 9. Tumor deoxyribonucleic acid content was analyzed by flow cytometry in 8 fresh samples from each primary tumor. Four patients had homogeneously diploid primary tumors, 5 had tumors with diploid and aneuploid samples, and all 8 tumor samples were aneuploid in 10 patients. Deoxyribonucleic acid analysis was unsuccessful in 1 patient. One patient with a diploid primary tumor died of an intercurrent disease. Three patients (16 per cent) had objective remissions and 1 had a long-lasting stable disease. Of the 4 patients with any response to medroxyprogesterone acetate treatment 3 had diploid primary tumors, and 1 had 8 diploid and 2 aneuploid samples in the primary tumor. The remaining 14 patients showed no response to treatment and had progressive disease (11 of these patients died within 14 months). All 14 patients had aneuploid primary tumors. The results indicate that tumor ploidy might be related to response to medroxyprogesterone acetate treatment. Deoxyribonucleic acid content seems to be an important parameter to consider in planning treatment of metastatic renal cell carcinoma.
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PMID:Deoxyribonucleic acid content and medroxyprogesterone acetate treatment in metastatic renal cell carcinoma. 214 89


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