Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirteen patients with metastatic melanoma and ten patients with advanced renal cell cancer (RCC) received interferon alfa-2a (Roferon-A) and vinblastine. In melanoma the interferon dose was 3-9 million IU i.m., escalated daily for 10 weeks, and in RCC the dose was 18 million IU three times a week i.m. The dose of vinblastine was 0.075-0.15 mg/kg every third week i.v. One of the ten evaluable patients with melanoma had partial remission (PR; 11%) and three presented no change (NC). Three of seven evaluable patients with renal cell carcinoma had PR (43%) and three NC. Duration of the remission was 10 months in the melanoma patients and 7+, 10+, and 7+ in the RCC patients. The three times a week schedule was better tolerated. The most common side effects were fever, fatigue, loss of taste, weight loss, and neutropenia. On the basis of these results it can be concluded that in melanoma the combination of daily administration of interferon and vinblastine is not effective, whereas in renal cell cancer interferon and vinblastine treatment given three times a week seems to be favorable.
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PMID:Combined interferon and vinblastine treatment of advanced melanoma and renal cell cancer. 318 Jan 44

Eleven patients received four consecutive weekly cycles of human recombinant interleukin 2 (IL-2) by continuous infusion for 4 days/week. Two dose levels were tested, 1 and 3 X 10(6) units/m2/day. Toxicities experienced by most patients included fever, rigors, fatigue, anemia, eosinophilia, and liver function abnormalities. All side effects from treatment reversed and no severe or life-threatening problems occurred. A marked lymphocytosis was seen following the 4 weeks of therapy. Fresh lymphocytes obtained during this lymphocytosis mediated enhanced destruction in vitro of a natural killer cell-resistant tumor cell line (Daudi). The increase in the absolute number of circulating lymphocytes and their enhanced ability to mediate direct lysis of Daudi targets resulted in a greater than 100-fold mean increase in cytotoxic potential by the end of IL-2 treatment. One patient, with renal carcinoma, who was treated at 3 X 10(6) units/m2/day experienced a sustained measurable response with greater than 50% regression of pulmonary and hepatic metastases. Five patients were retreated with a second course of IL-2, lasting 4 weeks. This therapy was well tolerated in four of these five patients, with similar immunological changes occurring. No further antitumor responses were seen in these patients. Thus, a relatively well tolerated immunotherapy regimen using IL-2 can induce dramatic increases in lymphocyte number and augment their in vitro antitumor reactivity.
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PMID:Clinical and immunological effects of recombinant interleukin 2 given by repetitive weekly cycles to patients with cancer. 325 45

The combination of Interferon and low-dose cyclophosphamide synergistically inhibits the growth of human breast cancer xenografts, explanted human non-small cell lung carcinoma, and other experimental tumors. To determine whether this combination would demonstrate clinical efficacy against refractory solid tumors, we used recombinant alpha-2b-Interferon, 10 MU/m2 subcutaneously three times per week, and cyclophosphamide, 25 mg orally twice daily, in 42 patients (25 renal cell carcinoma, 17 melanoma). Two patients were inevaluable due to premature removal from the study. The toxicity profile did not differ substantially from that of Interferon alone with malaise, fatigue, fevers, and chills predominating. Sixteen percent of patients experienced an alteration in mental status. Of 40 patients evaluable for response, there were two partial responders (one renal cell carcinoma, one melanoma) and four minor responders (all renal cell carcinoma). The responder with melanoma had previously failed therapy with dacarbazine (DTIC). Seventeen patients remained stable for a median follow-up of 6 months. We conclude that this regimen is well tolerated; however, the combination of Interferon and low-dose cyclophosphamide used in this way does not appear to be superior to the same dose and schedule of Interferon used alone.
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PMID:Phase II trial of recombinant alpha-2b-interferon and low-dose cyclophosphamide in advanced melanoma and renal cell carcinoma. 327 75

Cytoplasmic lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (HBDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzymatic activities were measured in normal renal cortical tissue and in hypernephroma. Significantly lower activities were always found in tumoral tissue than in normal renal tissue. Their respective values (mean +/- SD) were: LDH, 4,333 +/- 747 (normal tissue) vs. 997 +/- 748 U/l (tumor); HBDH, 2,554 +/- 466 vs. 387 +/- 290 U/l; AST, 529 +/- 109 vs. 65 +/- 37 U/l, and ALT, 205 +/- 45 vs. 9.9 +/- 5.4 U/l. The LDH/HBDH ratio was significantly greater in tumoral (2.69 +/- 0.69) than in normal tissue (1.70 +/- 0.11). These results indicate that hypernephroma exhibits a low metabolic rate when compared to normal tissue. Their enzymatic activities suggest a decreased energy metabolism, predominantly of the anaerobic type, and a reduced synthesis of nonessential amino acids in the tumor. These findings could explain in part the slow growth rate of hypernephroma.
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PMID:Cytoplasmic enzyme activities in human hypernephroma compared with normal renal cortical tissue. 337 61

Human lymphoblastoid interferon (HLBI-alpha) or recombinant human leukocyte interferon (HLIF-alpha) was administered to ten patients suffering from renal cell carcinoma at a daily dose of 5 X 10(6) units. The efficacy of interferon was assessed in nine patients who had received HLBI-alpha or HLIF-alpha for more than eight weeks. One patient (11%) demonstrated complete response (CR), three patients (33%) showed no change and five patients (56%) continued to have progressive disease. CR was obtained after 30 weeks under HLBI-alpha and FT-207 combination therapy. The main side effects were fever, anorexia, general fatigue and hematologic toxicities. Cessation of interferon therapy due to side effects was necessary in three patients. In conclusion interferon is one of the most valuable agents in the treatment of renal cell carcinoma.
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PMID:[Therapy of renal cell carcinoma. 3. Interferon therapy]. 361 21

Natural interferon-alpha preparation "Sumiferon" was recently developed in Japan. This is a human lymphoblastoid interferon (HLBI) preparation. Like other interferon preparations, this preparation showed both direct and indirect antitumor effect and the toxicities were moderate. The phase I-II studies were carried out in 38 major institutions in Japan. In the phase I study in 5 patients with advanced breast cancer, the maximum tolerated dose (MTD) was found to be 12 X 10(6) units/day given for 1 month. In the phase II study, HLBI was given in at 3 approximately 6 X 10(6) units/day. Out of 391 cases, 280 were evaluable. Complete and partial responses (CR and PR) were observed in 40 (14.3%) out of 280 evaluable cases, including 11 (19.6%) out of 56 renal cell cancer, 14 (19.2%) out of 73 multiple myeloma, and 9 (17.3) out of 52 malignant lymphoma among others. Major side effects observed were: fever (69.8%), gastrointestinal disturbances (31.4%), leukopenia (30.7%), thrombocytopenia (27.8%), hepatotoxicities (23.6%) and general fatigue (22.1%). Sumiferon seemed to be one of useful antitumor drugs effective against renal cancer.
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PMID:[Introduction of natural interferon-alpha "Sumiferon"]. 363 77

Alpha interferons are biological response modifiers that regulate immune function, slow cell proliferation, and inhibit virus replication. Large supplies of purified preparations are now available for clinical trials. Common toxicity includes an influenza-like syndrome to which tolerance occurs after several doses, and chronic fatigue and anorexia that may be dose-limiting. Myelosuppression is mild. Alpha interferons have established clinical activity against several human cancers, including melanoma, Kaposi's sarcoma, multiple myeloma, non-Hodgkin's lymphoma, hairy cell leukemia, and renal cell carcinoma. These data and alpha interferon nomenclature are summarized in table form. Intranasal alpha interferon is effective in prophylaxis of common viral upper respiratory tract infections, although toxicity in long-term use is prohibitive. Short-term administration to high risk populations may be most useful. Optimal doses and schedules need to be determined for all indications.
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PMID:The new alpha interferons. 391 Mar 84

A case of pulmonary metastasis from renal cell carcinoma in which complete remission was achieved using interferon therapy is herein reported. A 54-year-old male underwent left nephrectomy following diagnosis of left renal cancer. Radiotherapy and hormonal therapy were performed postoperatively. Solitary pulmonary metastasis was found in the right lobe 4 months after surgery. The interferon (recombinant human leukocyte A interferon, rIFN-alpha A, Ro 22-8181) was initially administered i.m. at a dose of 3 X 10(6) units per injection every day. Marked response was observed one month after starting the interferon therapy (total: 183 X 10(6) U) and complete disappearance of the tumor was obtained 2 months after commencement of therapy (total: 345 X 10(6) U). The interferon was later injected at a dose of 6 X 10(6) U., 3 times a week because of general fatigue. The duration of complete response has lasted 8 months.
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PMID:[A case of pulmonary metastasis from renal cell carcinoma in which complete remission was achieved by interferon therapy (r-IFN-alpha A, Ro 22-8181)]. 394 13

Twenty patients with measurable metastatic renal cell carcinoma (RCC) were were treated with interferon alfa-2a (Roferon-A), 36 X 10(6)U intramuscularly 3 times weekly, alone (2 patients) or in combination with vinblastine, 0.10-0.15 mg/kg intravenously every 2 to 3 weeks. Objective responses in the lung, bone, liver, and lymph node metastases were seen in 6 of 18 evaluable patients. Dose reduction of interferon alfa-2a was necessary in 19 of the 20 patients due to intolerable flu-like side effects and fatigue. Bone marrow suppression and increase of gamma-GT represented the most often observed objective toxicity. The preliminary results of this combination treatment in RCC are promising and warrant randomized studies exploring the role of vinblastine. The dose of interferon alfa-2a should be reduced by 50% to avoid excessive toxicity and to maximize patient compliance.
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PMID:Recombinant interferon alfa-2a with or without vinblastine in metastatic renal cell carcinoma. 394 41

Because two of five patients with renal cell carcinoma in a Phase I study had partial response to recombinant alpha-2 interferon (IFN), we treated 26 patients with advanced renal cell carcinoma with a 3-month regimen of IFN. Patients were randomized to receive IFN either subcutaneously (2 X 10(6) IU/m2 3 times a week) or intravenously (3 X 10(7) IU/m2 for 5 consecutive days every 2-3 weeks). Patients whose disease was responding or stable were treated further, while those with progressive disease on subcutaneous treatment were offered intravenous therapy. Sites of metastasis included lung (14 patients), bone (7 patients), soft tissue (7 patients) and liver (2 patients). Twenty patients were evaluable for response. One patient had a partial response at the end of the third course of intravenous IFN and subsequently had complete disappearance of a 12 X 7 cm subcutaneous mass after the seventh course of treatment. The disease was stable in 13 patients including two minor responses, and six patients had progressive disease (5 with subcutaneous treatment; 1 with intravenous treatment) including one mixed response. All patients experienced early flu-like symptoms of fever, chills, and rigors during the first few days of treatment and most had mild to moderate fatigue. Three patients left the study because of fatigue, and one had an urticarial rash. From these results and our previous experience, it appears that IFN has activity against renal cell carcinoma with acceptable toxicity.
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PMID:Recombinant interferon alpha-2 (INTRON A) in a phase II study of renal cell carcinoma. 395 53


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