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)

Adequate wide excision of a primary cutaneous melanoma is associated with a 10-year cure rate of 85% when the tumor's depth is less than 1.5 mm (American Joint Committee on Cancer [AJCC] Stage I). However, 50% of patients with deep (> 4 mm) primary melanomas, 60-85% of those with regional lymph node metastases (AJCC Stage III), and 95% of those with metastases to distant sites (AJCC Stage IV) will experience recurrence, which is associated with a dismal prognosis. Adjuvant therapy of melanoma assumes that treatment will be more effective when the tumor burden is small. In the 1970s and 1980s, randomized trials tested the efficacy of chemotherapy, nonspecific immunotherapy, levamisole, and regional perfusion therapy in patients with AJCC Stage II and III melanoma. Dacarbazine (DTIC) alone or in combination with other chemotherapeutic drugs or with nonspecific immunotherapy did not significantly improve disease free or overall survival. Of the four levamisole trials, only the study conducted by the National Cancer Institute of Canada revealed a reduction in recurrence and mortality; however, this reduction was not significant by multivariate analysis. The value of regional perfusion therapy following resection of high risk extremity melanomas is currently being determined by multiinstitutional studies conducted by the World Health Organization and the North American Perfusion Group. Multi-institutional trials also are examining the adjuvant role of interferon-alpha in patients with deep (> 3 mm) primary melanomas or positive regional lymph nodes; results should reveal its optimum dose and duration of treatment (3 x 10(6) U for > or = 2 years versus 10 x 10(6) U/m2 for 1 year, subcutaneously 3 times a week) and its impact on survival. A randomized trial of interferon-gamma undertaken by the Southwest Oncology Group was discontinued after interim analysis indicated an adverse effect. Phase II trials indicate that active specific immunotherapy can alter the natural course of AJCC Stage III and IV melanoma following surgical resection of nodal or distant metastases. Upcoming results of Phase III trials will establish the role of active specific immunotherapy for adjuvant treatment of patients with resected AJCC Stage III and IV melanoma.
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PMID:The role of adjuvant therapy in melanoma management. 780 1

Therapeutic effect of a vaccinia colon oncolysate prepared with interleukin-2 (IL-2) gene-encoded vaccinia virus (IL-2VCO) in combination with recombinant interferon-alpha (IFN-alpha) was studied in a syngeneic murine CC-36 colon hepatic metastasis model. Treatment with this IL-2VCO+IFN-alpha produced a higher survival rate (90% on day 60 after tumor transplantation) in mice having CC-36 hepatic metastases when compared to treatment with IFN-alpha (0%), VCO+IFN-alpha (0%), or IL-2VCO (11%). The only treatment that produced a survival rate similar to the survival rate of IL-2VCO+IFN-alpha was VCO+IL-2 + IFN-alpha (survival rate was 67%). The cause of the prolonged survival with the IL-2VCO+IFN-alpha treatment was identified as the reduction of CC-36 hepatic metastases (mean liver weight 1.31 g and mean tumor nodules 2). This reduction was significant when compared to IL-2VCO (1.58 g and 11), VCO+IFN-alpha (1.96 g and 53), and IFN-alpha (2.24 g and 91) treatments. The mechanism of the induction of antitumor response by the VCO+IL-2+IFN-alpha treatment was analyzed by measuring the direct cytotoxic activity of IFN-alpha on CC-36 tumor cells and by measuring the induction of cytolytic T-cell activity against CC-36 tumor cells. Results suggest that IFN-alpha produced minimal direct cytotoxic activity against CC-36 cells; however, the IL-2VCO+IFN-alpha combination therapy induced an enhanced cytolytic T-cell activity against CC-36 tumor cells (85.1% at E:T 100:1) when compared to other treatments (IL-2VCO 26.3%, VCO+IFN-alpha 13.4%, and IFN-alpha alone 6.3%). In addition, the role of T-cell subsets for the induction of antitumor immune response was analyzed in a survival study that used CD8-positive T cell-depleted mice. It was found that the survival rate was affected in mice depleted with CD8-positive T cells and treated with IL-2VCO+IFN-alpha when compared to control mice which had no T-cell depletion and were treated with IL-2VCO+IFN-alpha. This study suggests that the addition of IFN-alpha along with IL-2VCO increased the survival rate of mice having CC-36 hepatic metastases through the induction of CD8-positive T cells. Furthermore, this study confirms that IL-2VV can be used as a substitute for recombinant IL-2 in cytokine-augmented active specific immunotherapy.
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PMID:Immunotherapy of a vaccinia colon oncolysate prepared with interleukin-2 gene-encoded vaccinia virus and interferon-alpha increases the survival of mice bearing syngeneic colon adenocarcinoma. 788 37

Twenty-three patients with advanced renal cell carcinoma were treated with subcutaneous injections of interleukin-2 (IL-2) and interferon-alpha (IFN-alpha). IFN-alpha (5-10(6) U/m2) was injected on day 1 of the 1st week of a treatment cycle of 6 weeks and high doses of IL-2 (20.10(6) IU/m2) on days 3, 4 and 5. In the 2nd and 3rd week IFN-alpha (dose as above) and low doses of IL-2 (5.10(6) IU/m2) were injected on days 1, 3 and 5. The treatment from the 4th to the 6th week corresponded to that of the 1st to 3rd week. In cases of remission or stable disease the treatment schedule was repeated as a rule once or twice. In 12 of the 23 cases nephrectomy had been carried out previously. Complete remission lasting 4 + months and partial remission lasting 2 months were achieved in two patients with lung and skeletal metastases. A stable state of the disease lasting 1-7 + months was observed in 11 cases. Ten patients showed progression of the disease after the first treatment cycle. Thus, the overall objective response rate was 9%. The side effects were only slight and corresponded to WHO toxicity grade I (n = 8) and grade II (n = 15). In two cases the first treatment cycle could not be finished.
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PMID:[Treatment of advanced renal cell carcinoma with subcutaneous administration of interleukin 2 and interferon-alpha]. 797 33

This study was to define the efficacy of ifosfamide, mesna, carboplatin, and etoposide (ICE) in patients with metastatic non-small cell lung cancer (NSCLC). From September 1990 to October 1991, 33 patients were treated with ifosfamide/mesna 1.25 g/m2/day and etoposide 80 mg/m2/day intravenously from days 1 to 3, and carboplatin 300 mg/m2 on day 1 every 4 weeks. There were 20 male patients and 13 females. The median age was 65 (range: 38-79). Seventeen patients had a performance status (PS) of 0 or 1, and 16 had a PS of 2 or 3. All had measurable diseases. Nine had initial treatment for localized disease with concurrent radiation, 5-fluorouracil, and interferon-alpha 2b and four had radiation only. None had received chemotherapy for metastatic disease. There were nine partial responses (PR) (27.3%, 9/33) with a median response duration of 8 months (range: 2-16 months). Five patients had stable diseases (SD), which lasted for 3, 6+, 7+, 10+, or 13.4 months. The median survival was 8 months for PR and SD and 4 months for the entire group. Patients with PS of 2 or 3 were less likely to respond (18.8% vs 35.3%) and had a shorter median survival (2.7 months vs 6 months) than patients with better PS. Dose-limiting toxicity was myelosuppression. Seventeen (51.5%, 17/33) patients developed grade III-IV leukopenia with four septic episodes and three septic deaths. Grade III or IV thrombocytopenia was seen in five patients. Patients with prior radiation were significantly more prone to develop leukopenia (P < .005). Gastrointestinal toxicity was mostly mild. No neurologic or genitourinary toxicity was observed. In conclusion, ICE is active in patients with advanced NSCLC and good PS. Besides myelosuppression, it is well tolerated. Further study is indicated to evaluate if granulocyte-colony stimulating factor can reduce myelosuppression from ICE in good PS patients.
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PMID:Phase II study of ifosfamide, carboplatin, and etoposide in patients with advanced non-small cell lung cancer. 797 71

Six months after nephrectomy for renal-cell carcinoma and during treatment with interferon-alpha and vinblastin, a 70-year-old patient developed necrotizing Raynaud's phenomenon in both hands (at first: pain, livid skin and hyperhidrosis; later: painful acral ulcers; finally: trophic changes plus almost complete impairment of mobility and fine movements in both hands). These changes persisted even after the end of chemotherapy and despite several months on aspirin, naftidrofuryl, nitrates and glucocorticoids, so that the patient's general health was seriously affected. Because repeated sympathetic blocks were efficacious for brief periods, bilateral transthoracic endoscopic sympathectomy (TES) was performed. The patient became free of pain at once, the acral ulcers healed within a few weeks and he could again use his hands. Until his death from advanced metastases 10 months later the Raynaud's phenomenon did not recur. This case suggests that sympathetic vasoconstriction is apparently involved in the maintenance and progression of malignant neoplasm-associated Raynaud's phenomenon. TES is recommended as a reasonable palliative measure in patients with limited life expectancy, as long as preceding sympathetic blockage has indicated likely success and the procedure is performed under intraoperative monitoring of acral and facial skin temperature.
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PMID:[Endoscopic transthoracic sympathectomy in a paraneoplastic Raynaud's syndrome]. 807 4

In order to investigate the effects of in vivo treatment with interferon-alpha (IFN-alpha) on melanoma antigens, a clinical EORTC trial (No. 18852) was accompanied by an immunohistological study. Twenty patients with melanoma metastases of skin and soft tissues, eventually also of the lung, who were treated with systemic IFN-alpha, were evaluated for a comparison of metastases before (40) and during (42) treatment. Representative cryostat sections were studied immunohistologically with a panel of monoclonal antibodies against differentiation antigens (HMW-MAA, K-1-2, NKI-beteb, M-2-10-15), progression markers (transferrin receptor, ICAM-1, VLA-2), histocompatibility antigens (HLA-A, B, C, HLA-DR) and the proliferation-associated nuclear antigen Ki67. We found an overall reduction of the proliferation-associated antigen Ki-67 (p < 0.01), and an increase in expression of HLA-DR (p < 0.05) and ICAM-1 (trend) during treatment. The intensity of expression of HLA-A, B and C antigens as well as pigmentation (p < 0.01) was found to be increased. Early progression (< or = 8 weeks after onset of treatment) was associated with a lack of phenotypic changes. The data suggest an independent modulation of proliferation, pigmentation, and antigen expression by systemic treatment of metastatic melanoma with IFN-alpha.
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PMID:Effects of systemic interferon-alpha (IFN-alpha) on the antigenic phenotype of melanoma metastases. EORTC melanoma group cooperative study No. 18852. 810 70

In this study, we describe the origin and characterization of a new metastatic tumor cell line (p11-R-Eb) obtained after i.p. passages of the nonmetastatic Eb lymphoma cells into DBA/2 mice. The p11-R-Eb cells exhibited the same morphology and in vitro growth properties and chromosome markers as the original Eb cells. FACS analysis of the p11-R-Eb cells also revealed a close similarity to the Eb cells. Moreover, the p11-R-Eb cells were specifically killed by anti-Eb cytotoxic lymphocytes. In spite of all these characteristics of the Eb line, p11-R-Eb cells metastasized to the liver when injected i.v. or s.c. in DBA/2 mice. Peritumoral interleukin (IL)-2 treatment resulted in a potent antitumor response in DBA/2 mice transplanted s.c. with p11-R-Eb cells. In contrast, the same IL-2 regimen did not significantly increase the survival time of mice transplanted with the highly metastatic ESb cell line. Combined IL-1/IL-2 treatments of established p11-R-Eb tumors resulted in a synergistic antitumor effect and in tumor regression in 70% of the injected mice. Similarly, combined peritumoral treatment with IL-1 and interferon-alpha/beta, which were poorly effective or ineffective as single cytokine therapy, resulted in a marked antitumor effect, and 30% of the mice were cured. Spleen cells from IL-1/IL-2-treated p11-R-Eb-cell-injected mice showed a marked antitumor activity when assayed in a Winn assay with homologous tumor cells. This antitumor activity was eliminated by preincubation of spleen cells with antibodies to CD4 and complement and markedly inhibited by anti-asialo GM1 antibodies. P11-R-Eb cells represent, therefore, a new tumor model which may be useful for investigating the relevant mechanisms which need to be activated to achieve a potent antitumor response to cytokine therapy in the DBA/2 mouse host.
Invasion Metastasis 1993
PMID:Isolation and characterization of a metastatic Eb-like tumor variant highly responsive to interleukin (IL)-2 and to combination cytokine therapy with IL-2/IL-1 beta and IL-1 beta/interferon-alpha/beta. 811 75

Pancreatic polypeptidioma, a pancreatic endocrine tumor, is an extremely uncommon disease and its clinical features and responses to therapy are not well known. We present a 33-year-old woman with disseminated pancreatic polypeptidioma, who subsequently showed various signs and symptoms of metastases, including bone pain, cranial nerve palsy, spinal block, and hematuria, and died 22 months after the presentation. Responses to various therapeutic regimens including hepatic arterial embolization, radiation therapy, systemic chemotherapy, and administration of interferon-alpha or somatostatin analogue, are discussed. Particular note in this case is a prompt response of bone metastases to the radiotherapy.
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PMID:Disseminated pancreatic polypeptidioma. 814 81

Recent clinical trials for the biological therapy of solid tumours have used recombinant human cytokines in combination with conventional chemotherapy. In patients with progressive metastatic renal cell carcinoma, we established a three-drug combination comprising interferon-alpha (IFN-alpha), interleukin-2 (IL-2) and 5-fluorouracil (5-FU), using a regimen which allows outpatient therapy. Treatment consisted of 8 weeks each of IFN-alpha [6-9 MU/m2 once to three times weekly subcutaneously (sc)] combined sequentially with IL-2 (5-20 MU/m2 thrice weekly sc for 4 weeks) and 5-FU [750 mg/m2 intravenously (i.v.) weekly for 4 weeks]. Among the first 35 patients treated, there were 4 complete (11.4%) and 13 partial responders (37.1%), with an overall objective response rate of 48.6% (95% confidence interval 32-66%). Regressions occurred in local relapse, in lung, lymph node, bone, pleural, renal and thyroid metastases. Median response duration was calculated at 7+ months. An additional 13 patients (37.1%) were stable throughout therapy and thereafter (median of 6+ months). Response rate of this three-drug combination regimen compared favourably with single agent IFN-alpha (objective response rate approximately 16%) and against the sc IFN-alpha/IL-2 combination (objective response rate approximately 28%). Systemic toxicity was mild to moderate with no severe 5-FU-related mucositis and no dose-limiting adverse effects of sc IL-2. While the exact mechanisms of the potentially additive or synergistic effects of 5-FU and IFN-alpha/IL-2 remain to be established in more detail, it appears that the sequential use of IFN-alpha/IL-2 and IFN-alpha/5-FU in metastatic renal carcinoma further enhances the therapeutic index of IFN-alpha/IL-2-based biological therapy. Based on the present data, combined biochemotherapy may be a promising new approach to the therapy of advanced renal cancer.
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PMID:Interleukin-2 in combination with interferon-alpha and 5-fluorouracil for metastatic renal cell cancer. 826 Feb 64

We report on a 37-year-old woman with progressive lung and pleural metastases from a right nephroblastoma, who achieved partial remission with recombinant interferon-alpha. The drug was given subcutaneously at a dose of 5 mu. 3 times per week. The response was documented after 3 months of treatment and was maintained for at least 9 months. Although such a response has not been reported in the literature, this case suggests promising activity of recombinant interferon-alpha in relapsed nephroblastoma.
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PMID:Recombinant interferon-alpha efficacy in relapsed adult nephroblastoma: a case report. 828 39


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