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)

This is a phase I-II study of lymphoblastoid interferon (IFN-alpha-N1) combined with primary chemotherapy after cytoreductive surgery in patients with suboptimal stage III and stage IV epithelial ovarian carcinoma. Fourteen patients were treated initially with cyclophosphamide, doxorubicin, and cisplatin (CAP regimen) for two cycles, and IFN (alpha-N1) was added to this combination on day 2 of the third cycle. Patients then were divided into four groups, each group receiving differing doses of IFN ranging from 3 to 10 MU/m2 on each of days 2-5. A total of eight courses of chemotherapy was administered, six of which included interferon. Severe fatigue and malaise were the greatest dose-limiting toxicities associated with the interferon. However, severe bone marrow suppression also limited the administration of interferon. The results of this study suggest that the addition of interferon to the multiagent chemotherapy regimen of CAP is both unacceptable to patients and excessively toxic to the bone marrow. Because of the small patient sample and poor tolerance of the treatment, an accurate evaluation of therapeutic response could not be performed.
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PMID:Human lymphoblastoid interferon (IFN-alpha-N1) plus doxorubicin, cyclophosphamide, and cisplatin in the treatment of advanced epithelial ovarian malignancies. A phase I-II study of the Gynecologic Oncology Group. 198 44

A phase I trial of natural human beta-interferon (nHuIFN-beta) was initiated to evaluate its biological activity, maximum tolerated dose, and toxicity in patients with refractory malignancies. nHuIFN-beta was administered to successive groups of 4-6 patients as an i.v. bolus on days 1 and 4, for 4 consecutive weeks. Dose levels were 0.1, 1.0, 10, 30, 60, 100, and 200 x 10(6) units/m2. Thirty-five patients were entered, and 34 patients were evaluable for toxicity, immunomodulatory, and antitumor effects. Toxicity was mild to moderate and included fever and chills, fatigue, arthralgias, nausea, transient renal and hepatic dysfunction, and leukopenia. No dose-limiting toxicity was observed, and no responses were seen. Significant immunological changes included the following: an increase in natural killer activity on day 5 when compared to pretreatment values (P less than 0.01) and an increase in activated T-cells (CD3+/HLA-DR+) with increasing doses of nHuIFN-beta (P less than 0.01). Pharmacokinetic data demonstrated a short alpha half-life of 12.1 +/- 2.5 (SE) min and a beta half-life of 129.7 +/- 14.7 min. Neutralizing serum antibodies were detected in 2 of 27 patients receiving nHuIFN-beta. In conclusion, toxicity of nHuIFN-beta given twice weekly was moderate, and further dose escalation is possible. The immunological changes and pharmacokinetic behavior of nHuIFN-beta resemble those reported with rHuIFN-beta ser.
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PMID:Phase I trial of natural human interferon beta in metastatic malignancy. 198 23

Data are available on the principal side effects of individually administered biological response modifiers (BRMs). However, studies on physical symptoms secondary to multiagent regimens (i.e., combinations of BRMs and of BRMs and chemotherapy) are just now appearing in the literature. The combinations of alpha interferon and 5-FU and of alpha interferon and interleukin-2 (IL-2) are the focus of this paper. Published and unpublished reports of side effects associated with these combinations are reviewed, and resulting quality-of-life (QOL) issues examined. Physical side effects that may affect QOL are flu-like symptoms, gastrointestinal (GI) toxicities, and fatigue, which may alter social, physiological, and psychological function and negatively influence the perception of QOL. Nursing interventions to improve these reactions include awareness and assessment of the patient's perception of QOL and strategies to alleviate the symptoms. Numerous opportunities exist for nursing research on improved symptom management and on QOL in combination biotherapy regimens.
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PMID:Physical symptoms of combination biotherapy: a quality-of-life issue. 206 57

A new case of IgE myeloma is described. A 77-year-old woman presented with bone pain and fatigue. Serum protein analysis revealed a paraprotein of the IgE kappa type; bone marrow aspirate and immunofluorescence confirmed the diagnosis; ultrastructural examination showed immature plasma cells. Treatment with prednisone, melphalan, cyclophosphamide and interferon alfa did not produce any improvement and the patient died 5 months after diagnosis. The patient's clinical and laboratory data are compared with those of IgE myeloma cases reported in the literature.
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PMID:A new case of IgE myeloma. 201 30

Thirty-nine patients with epithelial ovarian cancer admitted to the Division of Medical Oncology of the Medical School II of Naples were given 159 courses of alpha 2b interferon (30 Mil./sqm IU) intraperitoneally from October 1986 to November 1989. IFN was generally administered every three weeks, but six patients received the drug weekly at the same dose, for an additional period. In 15 patients IFN was added to standard systemic chemotherapy as first line treatment; the remaining patients, all pretreated (22 with minimal and 2 with no residual disease), received an intraperitoneal multidrug treatment combining IFN, cisplatin and mitoxantrone. Peritoneal access was achieved through a temporarily implanted 18 gauge catheter and the drug was instilled in a large fluid volume (2,000 ml) to ensure wide spread and uniform distribution. IFN was well tolerated: only one patient had to discontinue treatment because of severe fatigue. No major complication related to catheter implantation or function occurred. 3/15 untreated and 11/20 pretreated patients, evaluable for response, achieved a pathological complete response (pCR). In view of IFN's lack of significant toxicity and the safety and tolerability of a temporary small gauge catheter for peritoneal access, intraperitoneal chemotherapy including IFN should be useful in ovarian cancer patients with minimal or absent disease after first-line systemic treatment.
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PMID:Alpha 2b interferon (IFN) by intraperitoneal administration via temporary catheter in ovarian cancer. Preliminary data. 205 Jan 63

Pentostatin, a novel inhibitor of adenosine deaminase, has shown activity in various lymphoid malignancies of both the T and B cell lineage. This agent has unique side effects and in general myelosuppression has been mild. Interferon has both antiviral and antineoplastic properties. This agent has shown activity in hairy cell leukemia, chronic granulocytic leukemia, low grade lymphoma, and myeloma. Side effects from interferon are in general dissimilar to those that have been seen with pentostatin and in particular myelosuppression has not been a major toxicity with low doses of interferon. This current trial explored the combination of pentostatin and interferon in hematologic malignancies. Fifteen patients were enrolled in this phase I trial at a fixed dose of pentostatin of 4 mg/m2 biweekly and interferon at doses of 0.5, 1, 2, or 4 million units/m2 of interferon. At the first three dose levels of interferon nausea and vomiting were the predominant toxicity and appeared to worsen with time on study. Fatigue also was seen at the lowest level of interferon and was severe enough to cause two individuals to discontinue the study medications. At higher dose levels of interferon, myelosuppression, nausea and vomiting, and fatigue were the predominant toxicities. One patient with hairy cell leukemia had a complete response and a second patient with T cell cutaneous lymphoma had a partial response which lasted for 6 to 7 weeks. The maximum tolerated dose of interferon with pentostatin in this patient population was four million units/m2.
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PMID:A phase I trial of alpha-interferon in combination with pentostatin in hematologic malignancies. 205 72

Human lymphoblastoid interferon-alpha was administered intramuscularly at a dose of 5 x 10(6) units/day to 20 metastatic renal cell carcinoma patients. For potentiating the antitumor effect of interferon, cimetidine was also given to them orally at a dose of 800 mg/day. The combination therapy obtained a complete response in three patients (15%) and a partial response in three (15%). Nine patients (45%) had stable disease and five (25%), progressive disease. All six patients who responded to the combination therapy had been nephrectomized and had pulmonary metastases. Two of them also had metastases to other sites (mediastinal lymph nodes and bone). The pulmonary metastases were significantly more receptive to interferon therapy than those at the other sites. The average times before a response was obtained were 2.2 months for a minor response, 2.7 months for a partial response and 3.0 months for a complete response, and the average duration of response was 26 months. The six patients who responded survived for a significantly longer period than the 14 non-responding patients treated with interferon in combination with cimetidine. The major toxicities encountered were fever, fatigue and anorexia due to interferon, and the combination therapy was well tolerated except in three patients. The results suggest that interferon-alpha and cimetidine combination therapy may be of use in the management of patients with metastatic renal cell carcinoma.
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PMID:Treatment of metastatic renal cell carcinoma with a combination of human lymphoblastoid interferon-alpha and cimetidine. 206 20

A dose optimization study was carried out with the aim of identifying the maximally tolerated dose of recombinant alpha interferon-2a (raIFN-2a) in combination with 5-fluorouracil (5FU). 5FU was given at the dose of 750 mg/m2 over a 4-hour infusion on day 1- - greater than 5 followed by 750 mg/m2 weekly i.v. bolus. Recombinant aIFN-2a was started at 3 x 10(6) IU subcutaneously three times/week. 12 patients with advanced colorectal carcinoma were included in the study. 10 patients had previously received chemotherapy for advanced disease. Severe fatigue, most likely attributable to rIFN, was the dose-limiting toxicity. The dosage of raIFN-2a could not be further escalated above 12 x 10(6) IU. At this dose level all patients required dose reduction due to fatigue, fever, myalgia and severe reduction of performance status.
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PMID:5-Fluorouracil and recombinant alpha interferon-2a in the treatment of advanced colorectal carcinoma: a dose optimization study. 209 Jul 72

We report 31 cases of renal cell carcinoma treated with interferon. Indicators defined as bidimensionally measurable mass were present in 20 cases, which included 19 cases with metastatic lesions and one case with primary site who did not receive nephrectomy. Treatment were performed with interferon-gamma in 9 cases, and with interferon-alpha in 14 cases. Of them, 3 cases received alpha-interferon following gamma-interferon treatment. Remained 11 cases had no evidence of disease after radical nephrectomy or surgical removal of metastatic lesions, and received interferon-alpha as post operative adjuvant therapy. In 18 evaluable cases, one case (6%) showed minor response; 8 cases (44%) no change and 9 cases (50%) progressive disease. Survival rates (Kaplan-Meier's method) of minor response and no change cases at 1, 2 years were 89%, 59%. Those of progressive disease cases were 22% and 11%, respectively. Of 11 cases received post operative adjuvant therapy, recurrence was observed in four cases (36%) with the mean follow up period of 11 months. Frequent side effects were fever (62%), leukocytopenia (56%) anorexia (38%), fatigue (26%). Efficacy of interferon to metastatic renal cell carcinoma in this study is limited. Further studies are required to determine the benefit of post operative adjuvant therapy with interferon.
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PMID:[Interferon alpha and gamma in the treatment of renal cell carcinoma]. 211 56

A phase I trial involving continuous infusion of both beta- and gamma-interferon (IFN-beta and IFN-gamma) was conducted in 20 patients in order to determine whether combinations of high doses of IFN-beta and IFN-gamma were tolerable when administered under conditions which mimic conditions of in vitro antiproliferative studies. Patients received a 5-day continuous infusion of IFN-beta/IFN-gamma, followed by a 9-day rest period. Two cycles were administered. Doses of IFN-beta/IFN-gamma were escalated between 4 dose levels, with 5 patients per dose level. Dose-dependent side effects, consisting primarily of constitutional symptoms typical of those experienced with IFN, were observed. The maximally tolerated dose of continuous IFN-beta/IFN-gamma infusion was 3 x 10(6) units of IFN-beta and 200 micrograms of IFN-gamma. Dose-limiting side effects consisted of severe headache, fatigue, fever, and hepatic toxicity. No clinical responses were observed. Serum IFN was measurable only at the highest 3 dose levels. Only 5 patients (4 at the highest dose level) had total serum levels which exceeded 50 laboratory units/ml (55, 63, 800, 800, and 550 laboratory units/ml, respectively). In order to confirm the biological effectiveness of this schedule, we measured IFN-inducible proteins prior to therapy, 24 h after the initiation of the infusion, and at the completion of the 5-day infusion. 2'-5'-Oligoadenylate synthetase, serum beta 2-microglobulin, neopterin, and p78 levels all increased significantly, and serum tryptophan decreased significantly within 24 h after the initiation of treatment (P less than 0.0001). A dose-response effect was observed for serum beta 2-microglobulin, neopterin, and p78 (P less than 0.02). We retrospectively compared the results of this trial with those of another IFN-beta/IFN-gamma trial in which IFN-beta and IFN-gamma were administered by i.v. bolus. Within the limitations of a retrospective comparison, continuous infusion was less well tolerated than our previous schedule of bolus administration 3 times/week. However, the continuous infusion schedule appeared to be more effective in enhancing 2'-5'-oligoadenylate synthetase levels in mononuclear cells. We conclude that tolerable doses of IFN-beta and IFN-gamma do not result in serum IFN levels which produce significant synergistic antiproliferative responses in vitro. This study and other findings suggest that, unless higher doses can be achieved, combinations of IFN-beta and IFN-gamma are unlikely to have significant therapeutic activity.
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PMID:Biological and clinical effects of the combination of beta- and gamma-interferons administered as a 5-day continuous infusion. 211 42


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