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)

Ten patients with metastatic colorectal cancer after resection of the primary tumor were treated with high-dose recombinant leukocyte alpha-2 interferon. For a period of 12 weeks the patients received up to 20 X 10(6) IU/m2 im twice weekly. Follow-up varied from 6 to 11 months after stopping treatment. All ten patients were evaluable for tumor response and toxicity. There was one partial response. Nine patients showed growth of metastatic marker lesions. Only three of these patients qualified as having progressive disease (greater than 25% increase in tumor mass). The response rate was 10%, with a 95% confidence interval of 0.3%-44.5%. Toxicity proved considerable and consisted of flu-like symptoms, fatigue, anorexia, and weight loss. Fatigue was the single most important dose-limiting factor. There were no drug-related deaths. Three patients died 3, 5, and 7 months after stopping treatment. Median survival was 18 months.
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PMID:Phase II trial of high-dose recombinant leukocyte alpha-2 interferon for metastatic colorectal cancer without previous systemic treatment. 388 27

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 total of 11 patients were treated on an escalating, single dose trial of recombinant gamma interferon (rIFN-gamma), 6 patients by the i.m. and 5 patients by the i.v. route of administration. Dose ranges within each individual were from 0.05 mg/m2 of IFN (1 mg greater than or equal to 10 X 10(6) units of IFN) escalating to 10 mg/m2. All dosages were delivered twice weekly and the i.v. dose was infused over 5 min. The most common toxicities encountered included fever, chills, fatigue, anorexia, and granulocytopenia. The influenza-like symptoms were very similar to those encountered with IFN-alpha but were generally less severe. The granulocytopenia was dose-related and transient with recovery generally seen within 48-72 h following administration of rIFN-gamma. Absolute granulocyte counts only rarely dropped below 1000 mm3. Hepatotoxicity was not observed. IFN levels were determined by both a bioassay and an enzyme-linked immunosorbent assay. By the i.v. route, the peak level of IFN activity could usually be seen at completion of the infusion with a serum half-life of 30 min. By the i.m. route, the peak level of serum activity was generally detected between 4-8 h with a serum half-life of 4.5 h after the initial elimination phase. Peak IFN levels appeared to correlate with maximum toxicity. One patient with melanoma had a 25% reduction in a cutaneous lesion, but there were no other minimal, partial, or complete responses.
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PMID:A phase I trial of recombinant gamma interferon in patients with cancer. 393 18

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

A clinical Phase I study of recombinant human interferon alpha A (Ro 22-8181) was performed in patients with malignant tumors; twenty of them received an American product and seven others a domestic product. Both products were administered in single intramuscularly injected doses of 18, 36, 50, 75 and 100 X 10(6)U. Main side effects included fever and influenza-like symptoms (headache, chill/shivering, general fatigue, lumbago), and digestive symptoms (anorexia, nausea/vomiting). Numbness of fingers or limbs and somnolence were also observed in higher dose groups, but these symptoms all disappeared on the day of administration or by the 3rd day after administration. Abnormal laboratory findings included leukopenia, granulocytopenia, lymphocytopenia, thrombocytopenia and increased GOT/GPT/LDH, but these returned to normal by the 10th day after administration. The peak blood concentration was correlated with the dose, falling to the base line 72 hr after administration. The American product and the domestic product were nearly comparable in the type and incidence of their side effects, and also produced generally comparable blood concentrations. Furthermore, increased anti-IFN-alpha antibody titer was not observed in any of the patients; and the Prick Test proved negative in all of them. No significant changes were observed in any immunological parameters, either.
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PMID:[Phase I study of recombinant human interferon alpha A (Ro 22-8181) in patients with malignant tumors]. 400 81

Results of an ongoing clinical study of a mismatched double-stranded (ds) RNA, termed Ampligen, in patients with metastatic cancer are described. In a pilot study of Ampligen (lot 1) involving mostly hematologic malignancies, patients received cumulative doses up to approximately 450 mg without untoward effects. Evidence of biologic/antitumor effects was observed (3/5 patients) by monitoring tumor-specific markers or tumor cell morphology. In patients with solid tumors receiving lot 2, Ampligen cumulative doses over 4 g were well tolerated. The drug was given by intravenous infusion (10-80 mg/infusion, twice weekly), in some instances for more than 1 year, without clinically significant side effects. Specifically, no evidence of hematologic, liver, or renal toxicity, which was previously noted with other dsRNAs, was observed. Side effects consisted of occasional mild fatigue or flu-like symptoms. Fever, when encountered, was transient and low grade (less than 100.5 degrees F). Importantly, an analysis of patient sera for dsRNA antibodies revealed that no patient had evidence of specific antibodies directed against Ampligen. Other dsRNAs cause up to a 60% incidence of antibody formation. Additionally, a novel method was developed to monitor Ampligen blood levels. In a survey of seven patients, Ampligen had a mean plasma half-life of 23 min. Ampligen administration can also result in activation of both natural killer (NK) cells and a lymphocyte, interferon-associated, intracellular enzyme. Dose-dependent antitumor effects were seen in several solid tumors; in doses of 10-40 mg, 3/9 patients showed stable disease for up to 1 year. At the 80-mg dose level, 2/5 patients showed tumor regressions (mixed and partial responses).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical studies with ampligen (mismatched double-stranded RNA). 408 35

Twenty-seven patients with non-reticuloendothelial malignancies were treated with a single intramuscular injection of recombinant leukocyte alpha 2 interferon (rIFN) to assess clinical tolerance and define a maximum tolerated dose. A single patient in each of six increasing dosage groups (0.3 X 10(6) IU, 1 X 10(6) IU, 3 X 10(6) IU, 10 X 10(6) IU, 30 X 10(6) IU, 100 X 10(6) IU) received a low dose (0.01 X 10(6) IU) and served as a control for subjective and objective toxicity measurements. Severe fatigue proved dose-limiting at 100 X 10(6) IU, and all dosages above 3.0 X 10(6) IU produced one or more signs or symptoms, which typically resembled a 'flu-like' syndrome. Objective toxicity was mild to moderate (leukopenia, thrombopenia) and no toxicities were found not already known from work with interferon obtained directly from leukocytes. Evidence of an antitumor effect was apparent in 3/19 evaluable patients.
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PMID:A phase I clinical tolerance study of rDNA alpha 2 human interferon in patients with non-reticuloendothelial system malignancies. 635 14

This study was designed to evaluate the clinical tolerance to multiple IM injections of rDNA-produced human alpha-2 interferon (IFN) (Schering-Plough 30500) in patients with solid tumours. IFN was administered in escalating IM doses in separate groups of patients daily for 14 days and then twice weekly for a further 10 weeks. The dosage levels were 1, 3, 10, and 30 million U/injection. Subjective toxicity could be divided into two types, acute and chronic. The acute reactions took the form of an influenza-like syndrome consisting in chills, rigors, headache, tremor, nausea, vomiting, and myalgia. These symptoms were dose-related but tachyphylaxis developed with continued dosing. The chronic toxicity consisted of malaise, lethargy, fatigue, anorexia, and confusion. These symptoms were not so dose-dependent and tended to become more severe with prolonged treatment. Objective toxicity consisted of myelosuppression and liver dysfunction. Granulocyte counts below 1.0 X 10(9)/l were seen in three patients at the 30-million-U level, with platelet counts less than 100 X 10(9)/l in two of these. Elevation of the liver enzymes were seen in all five patients treated at 30 million U, but returned to normal after 1 week without IFN in all but one patient. A tolerable dose (IM) for phase II/III studies lies between 3 and 10 million U for daily scheduling and between 10 and 30 million U for twice-weekly injections.
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PMID:A phase I toxicity study of human rDNA interferon in patients with solid tumours. 646 93

Four patients with adult T-cell leukemia (ATL) and 4 patients with non-Hodgkin's lymphoma were treated with alpha-type interferon (Human Lymphoblastoid Interferon: HLBI). Treatment regimen consisted of 3 to 12 million units (MU) of HLBI given intramuscularly once daily. The total dose varied from 36 to 520 MU. Complete remissions were obtained in one of 4 patients with ATL and one of 3 patients with B-cell lymphoma. A partial remission was yielded in one patient with B-cell lymphoma. An overall response rate (CR + PR) was 37.5%. Toxicity included flu-like symptoms, myelosuppression, G-I tract symptoms, fatigue, high fever and hepatic disturbance. On the basis of this study, we have concluded that HLBI is effective for the treatment of ATL and B-cell lymphoma.
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PMID:[Effect of human lymphoblast interferon in adult T-cell leukemia and non-Hodgkin's lymphoma]. 660 14


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