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)

The combination of interleukin-2 (IL-2) and interferon-alpha-2a (IFN-alpha-2a) has synergistic bioactivity in numerous preclinical model systems. Thirty-nine patients with metastatic renal cell cancer were treated with continuous intravenous infusion IL-2 for 4-5 days plus intramuscular IFN-alpha-2a 2-3 days a week for 4 consecutive weeks. A 2- to 4-week rest period was permitted after each 4 weeks of treatment. Thirty-one of the 39 patients were assessable for response determination. Response rate (six complete+seven partial remissions) was 33.3% for all patients, or 41.9% when the analysis was restricted to the 31 evaluable patients. Three patients were unable to tolerate treatment due to anorexia, weight loss, and severe fatigue. This therapy was relatively well tolerated in the outpatient setting in the other patients despite fever, chills, fatigue, anorexia, and weight loss. There was no correlation of response with site of metastases or bulk of disease.
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PMID:Interleukin-2 and interferon-alpha-2a outpatient therapy for metastatic renal cell carcinoma. 831 97

The intravenous injection of interleukin-2 (IL-2) has appeared to induce tumor regression in metastatic renal cell carcinoma (RCC). IL-2 given subcutaneously has also appeared to be effective when it is administered in association with interferon-alpha (INF), but with a lower toxicity in comparison to the intravenous route of administration. The present study was carried out to evaluate the efficacy of a subcutaneous immunotherapy with IL-2 alone in metastatic RCC. The study included 30 consecutive patients affected by metastatic RCC, 14 of whom had been pretreated with INF plus vinblastine, while the other 16 patients received IL-2 as a first line therapy of their metastatic disease. IL-2 was given subcutaneously at a dose of 3 million IU twice/day for 5 days/week for 6 consecutive weeks, corresponding to one cycle of immunotherapy. No complete response was obtained. A partial response (PR) was achieved in 10/30 (33%) patients (median duration: 7 months, range 5-25), without any significant difference between patients pretreated with IFN and nonpretreated patients (4/14 vs 6/16). Response rate was significantly higher in nephrectomized patients than in those who did not undergo nephrectomy (10/25 vs 0/5; P < 0.01). Moreover, response rate was significantly higher in patients with performance status (PS) greater than 40% than in those with PS lower than 40% (10/23 vs 0/7; P < 0.01). A stable disease (SD) was obtained in 12/30 (40%) patients (median duration 5 months, range 3-13), while the remaining 8/30 (27%) progressed. The increase in lymphocyte and eosinophil mean number was significantly higher in patients with PR or SD than in the progressed ones.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Immunotherapy with low-dose subcutaneous interleukin-2 in metastatic renal carcinoma]. 833 55

The effects of combination therapy including various antitumor agents and interferon on mice bearing hepatic metastases of colon carcinoma 26 were determined. Combined treatment with interferon-alpha A/D and carboplatin (CBDCA) was associated with a considerably more pronounced antitumor effect than was treatment with either drug alone. Murine interferon-beta and -gamma each also potentiated the antitumor activity of CBDCA. Combination therapy with interferon-alpha A/D and CBDCA also resulted in marked inhibition of hepatic metastasis of M5076 reticulum cell sarcoma. However, interferon-beta did not potentiate the antitumor activity of CBDCA against either subcutaneously implanted colon carcinoma 26 or pulmonary metastases of this tumor. Thus, in our model the combined administration of interferon and CBDCA was associated with a synergistic antitumor effect on hepatic metastases alone.
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PMID:Synergistic antitumor effects of carboplatin and interferons on hepatic metastases of colon carcinoma 26 and M5076 reticulum cell sarcoma. 837 Jun 55

Disseminated malignant melanoma is a very resistant tumor to therapy. Mechanisms of resistance to chemotherapy may be due to glutathione reductase and O6 alkyltransferase, two enzymes especially able to detoxify from alkylation. An interesting model is represented by dacarbazine in the treatment of melanoma with nitrosourea derivatives. Cytokines may come to play an increasing role in the combination with chemotherapy; interferon-alpha and interleukin-2, for example, seem to potentiate the action of chemotherapy in well-designed clinical protocols. Moreover, tumor necrosis factor-alpha was shown to be active in combination therapy with interferon-gamma and chemotherapy when administered by isolation perfusion. Targeting with monoclonal antibodies or melanocyte-stimulating hormone-alpha conjugated to cytotoxic agents represents a promising area. The discovery of a gene, designated MAGE1, coding for a peptide presented by HLA-A1 and able to specifically activate cytotoxic T lymphocytes may represent a unique approach to specific active immunotherapy for melanoma. The interference with integrins and adhesion molecules may play a role in the prevention of metastases. Some preclinical models seem to validate this approach. Current treatment of disseminated malignant melanoma involves chemotherapy often associated with other cytotoxic agents or cytokines, which may potentiate the antitumor effect. Other therapeutic issues reviewed concern targeting and immunotherapy. This review ends with a survey of biologic factors that may constitute new approaches to melanoma therapy.
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PMID:Disseminated melanoma, preclinical therapeutic studies, clinical trials, and patient treatment. 845 23

Within four years a 44-year-old man developed a glucagonorma syndrome with insulin dependent diabetes mellitus, weight loss, diarrhea, anemia and a marked superinfected eczema. He developed an organo-cerebral psychosyndrome with cognitive retardation and syncoptic disturbance of consciousness, followed by a tetraspasticity with tetraparesis, micturition difficulties and fecal incontinence. There were a general cerebral atrophy as verified by means of MRT and signs of a demyelinating cerebral disease. The plasma concentration of glucagon was 48 fold elevated to 8,536 ng/l. By means of ultrasonography, CT, ERCP, and angiography a tumorous mass of the corpus and tail of the pancreas, 61 x 32 mm in size, was found with signs of infiltration into the region of the aorta and the splenic vein. Furthermore the liver showed diffuse partially cystic metastases. The diagnosis was certified by fine needle biopsy and histologic examination with Grimelius straining. A thrombosis of the femoral vein was detected by CT. The patient was treated by a debulking resection of the corpus and cauda of the pancreas combined with splenectomy and a drug therapy using octreotide. All paraneoplastic symptoms could be widely reduced. Plasma glucagon concentration decreased from 2,200 ng/l to 600 ng/l. Because of a liver enlargement due to the growth of metastases he was successfully treated with dacarbazine 250 mg/m2 per day during six monthly cycles for five days and interferon-alpha 3 x 3 millions units per week for six months followed by a normalization of the liver volumen.
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PMID:[Paraneoplastic spastic tetraparesis in glucagonoma syndrome. Successful therapy with octreotide, dacarbazine and interferon-alpha]. 892 39

The melanosomal protein gp100 was recently described as an antigen associated with tumor rejection in adoptive immunotherapy using tumor-infiltrating lymphocytes. In this study, we investigated whether the expression of gp100 in melanoma cells correlates with responsiveness to treatment with interferon-alpha and interleukin-2. Using the monoclonal antibody HMB-45 recognizing gp100, we examined metastatic tissue resected before therapy in 44 patients with melanoma including 9 patients with subsequent complete or partial remission. A very heterogeneous pattern of gp100-expression was found between patients, but the percentage of gp-100 positive cells in different metastases resected from the same patient was rather constant. This suggests that the gp100 expression determined in a single metastasis may be judged as being representative for other metastatic lesions of a patient. We found no correlation between expression of gp100 and responsiveness to subsequent immunotherapy. Our results show that the lack of gp100 before therapy is not associated with decreased responsiveness to subsequent cytokine treatment.
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PMID:Expression of gp100 in melanoma metastases resected before or after treatment with IFN alpha and IL-2. 894 77

Tolerability of approximately 30 anticancer drugs vary by 50% or more according to circadian rhythms in mice or rats. Despite pharmacokinetics parameters of cytostatic drugs vary according to dosing time in rodents, cellular rhythms appear as the main mechanisms of their chronopharmacology: circadian changes in enzymatic activities involved into fluoropyrimidine (5-fluorouracil-5-FU, or floxuridine-FUdR) catabolism (dehydropyrimidine dehydrogenase) or anabolism (thymidine kinase), rhythms in reduced glutathione, involved into cellular protection against cytotoxic effects of alkylating drugs, platinum complexes and anthracyclines, rhythms in cellular proliferation of rapidly renewing tissues, such as bone marrow or intestinal tract. Furthermore, chemotherapy injection at the least toxic time allows to increase its antitumor efficacy against several transplanted rodent tumor models. Extrapolation of these results for improving therapeutic index of chemotherapy in cancer patients was based upon the hypothesis that rhythms in metabolism or proliferation of healthy tissues were tightly coupled to the circadian sleep-wakefulness cycle, both in rodents and in man. Programmable-in-time pumps allowed to test the clinical relevance of chronotherapy principle in patients with cancer metastases. Phase I clinical trials with 5-FU, FUdR, oxaliplatin-L-OHP, interferon-alpha and doxorubicin suggested that circadian-based chronomodulation of chemotherapy delivery rate both improved drug tolerability and allowed to increase its safe dose. Antitumor activity of such chronomodulated regimens, usually involving several drugs, appeared as superior to that achieved by standard protocols in Phase II clinical trials, especially in patients with renal cell cancer receiving FUdR and in patients with colorectal cancer treated with 5-FU, folinic acid (FA) and L-OHP (so called chrono-FFL regimen). A randomized european multicenter trial validated the clinical relevance of the chronotherapy principle in 278 patients with metastatic colorectal cancer: chrono-FFL was compared to flat FFL infusion and resulted in 2 to 10 times fewer severe toxic effects and a near-doubling of its antitumor efficacy, objective response rate being 51% with chrono-FFL and 30% with flat FFL (p < 0.001). These results have warranted to test further the relevance of chronotherapy in patients with breast, lung or pancreatic cancer metastases and to develop basic research on the role of biological rhythms upon cancer processes.
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PMID:[Chronopharmacology and chronotherapy of cancers]. 897 20

A 52-year-old man consulted our hospital with a right abdominal mass. Imaging diagnosis revealed a 10.5-cm right renal tumor and bilateral adrenal masses (7 cm on the left side and 2.5 cm on the right). A radical nephrectomy and bilateral adrenalectomy demonstrated renal cell carcinoma with metastases to bilateral adrenal glands. Despite prophylactic treatment with interferon-alpha, a swollen left cervical lymph node and a left renal mass, which seemed to be metastatic lesions, developed respectively 6 and 33 months postoperative. He is alive with disease at 40 months.
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PMID:[A case report of renal cell carcinoma with bilateral adrenal metastases]. 908 48

Interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) were both administered subcutaneously (SC) in combination with intravenously (IV) applied 5-fluorouracil (5-FU) for the treatment of patients with metastasized renal cell carcinoma (RCC). The therapy protocol consisted of a treatment cycle of 8 weeks, which could be carried out in an outpatient regimen. The IFN-alpha was given in each of the 8 weeks (6-9 MU/m2 once to three times weekly SC) combined sequentially with IL-2 (5-20 MU/m2 three times weekly SC for 4 weeks) and 5-FU (750 mg/m2 IV weekly for 4 weeks). Among the 30 consecutive patients treated, in 2 cases a complete, and in 9 cases a partial, remission was achieved in patients with mostly lung and skeletal metastases, with an overall objective response rate of 37%. Mean response duration was 8 months (range 3-18 months). A stable state of the disease lasting 3-18 months was observed in 10 cases. The side effects were only slight and corresponded to toxicity grade I (n = 2), grade II (n = 22) and grade III (n = 6), according to the WHO classification. In conclusion, this triple-drug biochemotherapy demonstrated significant clinical effectiveness comparable with that of an aggressive IL-2 treatment regimen (applied IV), but without its high toxicity.
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PMID:[Immunochemotherapy of metastatic renal cell carcinoma with interleukin 2, interferon-alpha and 5-fluorouracil]. 912 81

The incidence of malignant melanoma continues to rise steadily in the United States, with approximately 40,300 new cases expected in 1997. A significant number of patients with deep primary lesions or regional lymph node metastases are at high risk for developing recurrent, metastatic disease despite adequate surgical intervention. Therefore, approaches to adjuvant therapy including immunotherapy, such as interferon, levamisole, and vaccines and chemotherapy and chemoimmunotherapy have been investigated in high-risk patients. The key adjuvant trials are reviewed, with emphasis placed on randomized trials. High-dose interferon-alpha has recently been shown to modestly improve disease-free and overall survival in a prospective randomized trial of high-risk patients and has been approved by the FDA for this indication. Vaccines, which currently remain experimental, may prove to be equally effective but less toxic options for adjuvant therapy. Also, the identification of more high-risk patients who might benefit from adjuvant therapy may be facilitated by sentinel lymph node biopsy and the reverse-transcriptase polymerase chain reaction for tyrosinase.
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PMID:Adjuvant therapy of malignant melanoma. 930 94


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