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)

We evaluated the effects of the addition of escalating doses of tumor necrosis factor (TNF) to two fixed doses and schedules of a combination of interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) to determine the maximum tolerated dose of this three-cytokine combination and its feasibility as an outpatient regimen. Eighteen patients with metastatic cancer were enrolled. Each course consisted of 3 consecutive weeks of treatment with IFN-alpha 9 x 10(6) IU/m2/day intramuscularly (i.m.) or subcutaneously (s.c.) days 1, 3, and 5 each week for 3 weeks plus IL-2 continuous infusion 1 x 10(6) IU/m2/day (group A) or 3 x 10(6) IU/m2/day (group B) days 1-5 each week for 3 weeks. TNF was administered only during the first week of each course intravenously (i.v.) for 2 h on days 1-5. The dose of TNF was escalated (40, 80, 120 micrograms/m2) in cohorts of 3 patients. The most common side effects were fever, chills, and fatigue in all patients. Grade 3-4 toxicity included anemia (3 patients), thrombocytopenia (1 patients), arrhythmia (2 patients), pulmonary edema (3 patients),- and weight loss (1 patient). Five patients withdrew from study due to toxicity. The combination of the three cytokines is feasible as an outpatient regimen in one of the following combinations: (a) TNF 80 micrograms/m2/day as 2-h infusion on days 1-5 + IL-2 1 x 10(6) IU/m2/day continuous infusion on days 1-5 for 3 weeks + IFN-alpha 9 x 10(6) IU/m2/day s.c. or i.m. on days 1, 3, and 5 for 3 weeks, or (b) TNF 40 micrograms/m2/day as a 2-h infusion on days 1-5 + IL-2 3 x 10(6) IU/m2/day continuous infusion on days 1-5 for 3 weeks + IFN-alpha 9 x 10(6) IU/m2/day s.c. or i.m. on days 1, 3, and 5 for 3 weeks.
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PMID:Phase I study combining tumor necrosis factor with interferon-alpha and interleukin-2. 934 39

Two cases of rare metastases from renal cell carcinoma are reported. The first case was in a 44-year-old man presenting with left exophthalmos. Radiological examination revealed left renal tumor with metastases to paraaortic lymph nodes, left orbit, bone and lungs. Radical nephrectomy was performed. Pathological diagnosis was renal cell carcinoma, pT3aN2M1. The patient died of widespread pulmonary metastasis 5 months postoperatively. The second case was in a 59-year-old man with a complaint of tongue tumor. Histopathology of the enucleated tumor was suggestive of metastatic renal cell carcinoma. Computed tomographic scan revealed left renal tumor with regional lymph node metastasis. No other metastasis was found. Radical nephrectomy confirmed the pathological diagnosis of renal cell carcinoma, pT3bN1M1. He has been treated with interferon-alpha and has been free of recurrence for 10 months postoperatively.
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PMID:[Two cases of renal cell carcinoma detected by metastasis to another organ]. 936 44

During the past few years significant progress has been made in the treatment of cutaneous melanoma. These developments often involve the use of interferon-alpha (IFNalpha). Promising results have been reported in high risk patients using adjuvant treatment with high dose IFNalpha. A confirmatory trial of high dose IFNalpha and several adjuvant trials using low or intermediate dose IFNalpha are ongoing, and currently a standard regimen cannot be defined. High response rates have been reported in patients with metastatic disease with combination chemoimmunotherapy schedules. Randomized trials have to be performed in order to demonstrate a survival benefit over less toxic regimens. In this paper the current status of IFNalpha in the treatment of cutaneous melanoma is reviewed.
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PMID:The use of interferon-alpha in the treatment of cutaneous melanoma: a review. 961 Aug 61

The anti-tumoral activity of interleukin-2 (IL-2) is well-documented. Although the response rate with this cytokine is low, it appears to be improved when associated with interferon-alpha (INF-alpha) and/or cytotoxic drugs. Aim of this work was to study the efficacy and tolerance of an ambulatory treatment using subcutaneous, low-dose IL-2 with subcutaneous INF-alpha and chemotherapy. We report a multicenter study of ambulatory treatment combining subcutaneous (SC) low-dose IL-2 (9 x 10(6) IU) with SC INF-alpha-2a (3 x 10(6) IU) and cisplatin (100 mg/m2) in 33 patients (13 women and 20 men, 22 to 66 years of age) with metastatic malignant melanoma. Metastases were mainly nodal (54.5%) and pulmonary (51.5%). For 81.8% of patients, this therapy constituted the firstline treatment. The overall response rate at the end of the first maintenance course was 30.3% (3 complete responses and 7 partial responses). Adverse effects were observed in 28 patients (84.8%), but were most often minor (grade 1 or 2 on the WHO toxicity scale). The results confirmed the good tolerance to SC IL-2 and its suitability for ambulatory therapy, as well as the potential benefit of associating IL-2 with cisplatin in the treatment of metastatic melanoma (a possibility considered in two previous studies).
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PMID:Subcutaneous interleukin-2 and interferon-alpha therapy associated with cisplatin monochemotherapy in the treatment of metastatic melanoma. 964 95

Colorectal cancer is one of the most frequent cancers in the western world. Approximately half of the patients will die of their disease because of metastases. The most active cytotoxic agent used to date is 5-fluorouracil (5-FU). However, clinical responses are achieved only in a minority of patients. Based on the current knowledge of the mechanism of action of 5-FU, many attempts have been made to improve the clinical results. These include the use of biochemical modulators and different methods of administration, and these are the subject of this review. Specifically, of five different modulators, i.e. leucovorin, methotrexate, interferon-alpha, N-(phosphonacetyl)-L-aspartate and trimetrexate glucuronate, the biochemical background and the clinical results obtained with these modulators are discussed. In order to get more insight, an overview of the 5-FU metabolism has been given. In addition, the different methods of systemic administration of 5-FU as well as possible mechanisms underlying 5-FU resistance are described.
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PMID:5-Fluorouracil in colorectal cancer: rationale and clinical results of frequently used schedules. 966 May 32

Combined therapy of gemcitabine with interferons on patients with histologically confirmed metastatic renal cell carcinoma is reported. Patients had an unfavourable disease due to documented tumor progression after various interferon-alpha-based immunotherapy (26 weeks on average). The median number of metastatic sites was 6.1 per patient and 78% of the patients exhibited >/= 4 lesions. Nine evaluable patients received at least 6 doses of gemcitabine and 8 doses of interferon-gamma. Overall, therapy resulted in a remission rate of 15% (4 x partial response; 4 x minor response) for single measurable lesions (n=53). Remissions were more often found for lesions, that did not progress at baseline evaluation (n=30; OR: 20%), compared to 8.7% for sites in progression (n=23). However, as a result of therapy, 43.5% of the progressive lesions did not continue to progress. Although only one of nine patients finally overall achieved a minor remission and one patient a stable disease, the median time to tumor progression (6.1 months) and the median survival (13.5 months) was favourable. In conclusion, the combination of gemcitabine and interferon demonstrated cytotoxic and cytostatic effects on metastases of renal cell carcinoma at a tolerable toxicity, thus controlled clinical studies for first line therapy with gemcitabine and interferon are in progress.
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PMID:Treatment of renal cancer patients with gemcitabine (2',2'-difluorodeoxycytidine) and interferons: antitumor activity and toxicity. 976 5

ESb lymphoma cells injected i.v. into DBA/2 (H-2d) mice multiply rapidly in the liver and kill all mice in a few days. Adoptive transfer of allogeneic C57B1/6 (H-2b) tumor-immune or normal splenic lymphocytes to sublethally irradiated DBA/2 mice induced a marked antitumor state, graft-versus-leukemia (GVL), increasing the mean survival time 2-3-fold, but also induced an acute and lethal graft-versus host disease (GVHD). We have undertaken experiments to try to dissociate GVL from GVHD. Transfer of immune spleen cells induced a greater GVL than transfer of normal spleen cells with an equivalent to GVHD. Three to five million immune or normal CD8+ T lymphocytes were sufficient to induce both GVL and GVHD. Individual DBA/2 mice were labeled and followed. In mice undergoing GVHD, the spleens were repopulated by donor (H-2b) lymphocytes, and tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were present in the sera of 26 of 27 and 18 of 20 mice, respectively, together with increased amounts of TNF-alpha and IL-6 mRNA in their spleens. This was in contrast to DBA/2 mice receiving allogeneic cells but not developing GVHD. Both interferon-alpha/beta (IFN-alpha/beta) and IL-12, which had proven very effective in association with adoptive transfer of syngeneic immune T lymphocytes in inhibiting ESb metastases, enhanced GVHD when administered with allogeneic immune or normal spleen cells, and >90% of mice died. Intensive IL-2 treatment inhibited GVHD while maintaining GVL.
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PMID:Role of cytokines in GVL (ESb lymphoma) and GVHD after adoptive transfer of allogeneic T lymphocytes in mice. 978 5

In spite of their tumor's origin in the uveal tract, many patients suffering from advanced uveal melanoma are admitted to dermatological oncology units. Most patients with metastases from uveal melanoma receive treatments that were established for stage IV cutaneous melanoma. However, both the biology as well as the metastastic behaviour of this tumor is different from cutaneous melanoma. Lymphatic metastases do not occur, and hematogeneous metastases usually occur later and predominantly involve the liver. The prognosis is very bad ranging from 2 to 5 months. We describe three patients with advanced uveal melanoma who received immunochemotherapy containing interferon-alpha 2b, interleukin-2, and fotemustine. This therapy induced a partial response of more than 49 months duration in one patient, whereas for the remaining patients the disease progression could be stabilized for eight and 16 months, respectively. This therapeutic success is reflected by a prolonged survival of 14,43+, and 59+ months.
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PMID:[Immunochemotherapy of metastatic uveal melanoma with interferon alfa-2b, interleukin-2 and fotemustine. Case reports and review of the literature]. 985 52

Our results with concurrent biochemotherapy in patients with stage IV melanoma have been encouraging. Based on these data, we conducted a phase II study to determine the clinical and histological response rate to neoadjuvant concurrent biochemotherapy in patients with local-regional metastases of cutaneous melanoma (stage III). A total of 65 patients with biopsy-proven, measurable and potentially resectable local-regional disease (nodal, satellite/in-transit metastases and/or local recurrence) were treated with cisplatin 20 mg/m2 intravenously (i.v.) on days 1 to 4, vinblastine 1.5 mg/m2 i.v. on days 1 to 4, dacarbazine 800 mg/m2 i.v. on day 1 only, interleukin-2 9 MIU/m2 per day i.v. by 96 h continuous infusion on days 1 to 4, and interferon-alpha 2a 5 MU/m2 subcutaneously on days 1 to 5, repeated every 3 weeks. Patients underwent surgery after two to four courses of biochemotherapy. Those with tumour regression after two preoperative courses received two additional postoperative courses. Of the 64 patients assessable for clinical response, 28 (44%) had a partial response. Of the 62 patients whose response was assessed histologically, four (6.5%) had no evidence of viable tumour in the surgical specimen (pathological complete remission, pCR) and 27 (43.5%) had a partial response, giving an overall response rate of 50%. Tumour burden did not correlate with response, although patients who achieved a pCR had a significantly lower tumour burden (P = 0.02). Our phase II study indicates that neoadjuvant biochemotherapy is an active treatment for melanoma patients with local-regional metastases. However, it is unclear if biochemotherapy is more active than chemotherapy alone; phase III randomized trials are ongoing to answer this question in patients with stage IV disease.
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PMID:Phase II study of neoadjuvant concurrent biochemotherapy in melanoma patients with local-regional metastases. 991 17

Intercellular adhesion molecule-1 (ICAM-1) plays an important role in cell to cell interactions. In malignant melanoma, ICAM-1 expression correlates with malignant behavior. We used monoclonal antibodies, anti-ICAM-1, anti-CD4+, anti-CD8+, and anti-CD11c+ to study the effect of interferon-alpha (IFN-alpha) on the expression of ICAM-1 by melanoma cells in regional metastases and its correlation to the occurrence of CD4+, CD8+, and CD11c+ cells close to tumor cells and in the tumor stroma. We also estimated the expression of ICAM-1 and regressive changes in malignant melanoma metastases, correlating the duration of treatment to these effects of IFN-alpha. Twenty-three IFN-alpha-treated and 10 untreated patients with regional metastatic malignant melanoma were studied. The duration of IFN-alpha treatment influenced the expression of ICAM-1. In metastases from patients treated for 1 week only, 1 of 5 showed high expression of ICAM-1 compared with 6 of 11 of those treated for 3 weeks (p = 0.01, chi-square test for trend comparing untreated patients and patients with various durations of IFN-alpha treatment). In IFN-alpha-treated patients with low expression of ICAM-1, none of 7 metastases showed CD4+ cells infiltrating close to tumor cells, in contrast to 6 of 10 metastases expressing high amounts of ICAM-1 (p = 0.03). Similarly, the expression of ICAM-1 was found to correlate with the occurrence of CD8+ cells close to the tumor cells (p = 0.04). We also showed a correlation between ICAM-1 expression and histologic evidence of tumor regression (p = 0.02).
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PMID:Expression of ICAM-1 during IFN-alpha-based treatment of metastatic malignant melanoma: relation to tumor-infiltrating mononuclear cells and regressive tumor changes. 1009 Apr 2


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