Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004093 (asthenia)
 2,650 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biological response modifiers (BRMs) have greatly modified the immunotherapy of tumors. Interleukin-2 (IL-2) has brought about metastasis regression in some cases of malignant tumors, however, when given systemically, it results in high toxicity. More recently, the subcutaneous administration of IL-2 (combined with alpha-interferon, alpha-IFN) seems to be capable of offering the same chances of therapeutic response, but this time with a lower level of toxicity. The Authors report an evaluation of toxicity in 22 patients treated with a combination of IL-2 + alpha-IFN i.m. with or without chemotherapy. The side-effects present in the majority of cases were: fever, diarrhea and asthenia. Approximately 50% of the patients had nausea/vomiting, mucositis, skin rashes, and slight leukopenia. The following side-effects were noted to a much lesser degree, thrombocytopenia, alterations in hepatic and dizziness and cystitis. Only one patient reached 4th degree toxicity, with mucositis, asthenia and skin rash. All the other patients received the treatment without suspensions for toxicity. Biological evaluations will enable us to determine in the future, the cases which can benefit from therapeutic intensification and thus it would seem opportune at this time to use therapy with acceptable toxicity.
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PMID:Evaluation of toxicity in 22 patients treated with subcutaneous interleukin-2, alpha-interferon with and without chemotherapy. 128 42

Partially purified interferon alpha (IFN alpha) was administered to 50 patients with metastatic renal-cell carcinoma (RCC) studied for more than two years. Complete or partial remissions were observed in 26% of the patients. Duration of remissions range from two to 16 months (median, six months). No distinct prognostic factors were clearly identified in the responsive patients, but responses occurred more frequently in men with optimal performance status who had undergone nephrectomy and in whom the metastatic disease was confined to the lungs, pleura, or mediastinum. Leukopenia and granulocytopenia were useful markers of biological activity but did not predict tumor response. Side effects and toxicity at the dosage used (3 X 10(6) units intramuscularly daily) were well-tolerated and consisted predominantly of fatigue and asthenia. We concluded that IFN alpha is useful for palliating metastatic RCC, but no impact on survival was demonstrated. Further studies are required to determine the optimal dose, routes of administration, and treatment schedules.
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PMID:Phase II study of interferon alpha in metastatic renal-cell carcinoma: a progress report. 402 Apr 10

The efficacy of Human 6 IFN (HLIFN) given in a pulse fashion was determined in a phase II study. Ninety-one cancer patients were evaluated (9 myeloma, 12 breast, 14 prostate, 9 melanoma, 4 renal, 6 astrocytoma, 7 ovarian, 9 large bowel, 7 gastric, 14 head and neck). They all had advanced progressive cancer that was resistant to chemotherapy and/or radiotherapy. Patients were treated by intramuscular injection of 6 X 10(2) I.U./m2 for three consecutive days every four weeks. 84 patients were evaluable. Complete clinical response was obtained in 23 patients (4 myeloma, 2 breast, 5 prostate, 1 melanoma, 1 renal, 2 astrocytoma, 2 ovarian, 2 large bowel, 1 gastric, 3 head and neck). Partial responses were observed in 35 patients (3 myeloma, 7 breast, 6 prostate, 4 melanoma, 1 renal, 2 astrocytoma, 3 ovarian, 4 head and neck). Objective responses were related (P less than 0.01) to serum IFN level, with complete and partial responses (P less than 0.01) more commonly seen in those patients whose serum IFN levels at two hours were in the range of 1000 to 1650 I.U./ml. Side effects resulting from pulse IFN were acceptable for this group of patients and consisted of fever, transient chills, malaise and asthenia, and transient thrombocytopenia and leukocytopenia. The extent of fever was directly related (P less than 0.01) to response, and was most elevated in patients who achieved objective responses. IFN administered in a pulse fashion appears to be more effective than daily IFN and merits further evaluation.
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PMID:Clinical results of leukocyte interferon-induced tumor regression in resistant human metastatic cancer resistant to chemotherapy and/or radiotherapy-pulse therapy schedule. 405 26

Twenty-nine late chronic and accelerated phase chronic myelogenous leukaemia (CML) patients were entered in a pilot study designed to test the therapeutic efficacy of treatment with interferon-alpha (IFN-alpha) and low-dose cytosine arabinoside (ARA-C). IFN-alpha was administered at a dose of 2-10 x 10(6) IU/day and ARA-C at 15 mg/m2/day for 14 days each month. The treatment was well tolerated by 73% of the patients. Side effects were mainly asthenia, anorexia, anaemia and piastrinopenia. Haematological and cytogenetic responses were evaluated in the 19 patients who received more than 6 cycles. Four complete haematological response, 7 partial haematological response, 6 minor haematological response, 2 stable disease were obtained in this patient group. Two complete cytogenetic responses and 2 minor cytogenetic responses were detected in these patients. Suppression of secondary Ph' positive clones which appeared during the previous IFN-alpha treatment was documented in 3 accelerated phase patients after ARA-C was added to their IFN-alpha treatment. It would therefore seem that late chronic and accelerated phase CML patients benefit from combined IFN-alpha/ARA-C treatment and achieve haematological and cytogenetic responses not obtained during previous treatment without being exposed to undue toxicity. However, we cannot judge whether it offers any advantage in terms of survival.
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PMID:Interferon-alpha plus low-dose cytosine arabinoside in advanced phase chronic myelogenous leukaemia patients. 767 91

A randomized controlled multicentre trial was undertaken to assess the effectiveness of natural IFN beta (Frone) administered by intramuscular injection to chronic hepatitis B patients. Sixty-five HBsAg and HBeAg carriers with chronic hepatitis and intrahepatic HBcAg histologically proven by immunohistochemistry were included in the study. Fifty-nine patients completed the study: 30 of them (mean age 27 years, range 14-55 years, 16M/14F) were treated with 5 Million Units (MU)/m2 of Frone three times weekly for six months and 29 (mean age 28 years, range 14-59 years, 18M/11F) were not treated. The 2 groups of patients were similar in their clinical and histological (CAH/CPH ratio 25/5 and 20/9) characteristics. In the treated patients, a significant reduction in viremia was observed starting from the 6th month of the follow-up (p < 0.01), accompanied by a significant reduction of serum aminotransferase levels (p < 0.005). At the end of therapy serum HBeAg was undetectable in 7 of 30 (23%) treated patients and in 1 of 29 (3%) controls. Six months after the end of treatment 8 of 30 (26%) treated patients and 5 of 29 (17%) controls were HBeAg negative. A significant difference (p < 0.05) was observed in the rate of anti-HBe seroconversion between the 2 groups starting from the 8th month of follow-up. Mild side effects, namely fever < 38 degrees C and asthenia were observed in 20% and 37% of treated patients. In conclusion natural beta interferon given intramuscularly is effective in HBeAg positive patients suffering from chronic hepatitis B with optimal compliance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intramuscular natural beta interferon in the treatment of chronic hepatitis B: a multicentre trial. Italian Hepatitis B Study Group. 791 65

Interferon-alpha (IFN alpha) is often used for the treatment of renal cell carcinomas. The injections are frequently self-administered at home. To assess how this therapy was accepted by the patient we sent out a questionnaire. For the past 2 years until March 1993, this therapy was performed in our department on 52 patients, of whom 45 were selected for the study. All patients were informed of their disease and consented to the necessity of this treatment. Thirty-eight patients answered this questionnaire. Almost all patients injected this agent mainly by themselves. These findings suggested that they regarded this therapy as a strategy to be executed by themselves for the treatment of carcinoma. The main toxic symptoms in this therapy were asthenia, fever and loss of appetite. Leukocytopenia occurred in about half of the patients, of whom 1 patient required medication because of a rapid decrease in the white blood cell count shortly after inception of this therapy. The treatment was discontinued in 50% of the patients because of these adverse effects. Systemic toxicity disappeared after cessation of IFN alpha administration. Additionally, over 80% of the patients expressed concern about effectiveness, the duration and high cost of this therapy. The patients had to be repeatedly instructed about the method of disposing used needles and syringes. This study revealed that self injection of IFN alpha, which required strict management particularly at the initiation, can be performed at home. However, countermeasures must be taken against the side actions and an optimum regimen of IFN alpha should be established as soon as possible.
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PMID:[Present situation in self-injection therapy with interferon-alpha for patients with renal cell carcinoma]. 794 60

Biological response modifiers have been extensively investigated in the management of patients with cancer, but few data are available on tumors of the gastrointestinal tracts. To evaluate the feasibility and activity of the combination of interleukin 2 (IL-2) and beta-interferon (beta-IFN), 15 patients with colorectal cancer and 10 patients with hepatocellular carcinoma were treated with the following outpatient schedule: beta-IFN 3 x 10(6) U i.m. 3 times weekly from day 1 to day 14; IL-2 4.5 x 10(6) U s.c. every 12 for 5 consecutive days a week from day 7 to day 21, the cycles being repeated every 28 days. All of the patients had been previously treated with chemotherapy; 7 unresectable locally advanced, and 18 had metastatic disease. All of the treatment courses were administered in an outpatient setting. No grade 4 side effects were recorded. The worst side effects were grade 3 fever (4 patients) and asthenia (2 patients) requiring treatment discontinuation in 4 cases. Twenty-four patients were evaluated for response (14 with colorectal cancer and 10 with hepatocellular carcinoma). One partial response, 4 stable disease, 9 progressive disease were recorded among the colorectal patients; 4 stable disease and 6 progressive disease among the hepatocellular carcinoma patients. The median duration of stable disease was 3 months for hepatocellular carcinoma and 4 months for colorectal cancer patients. Our results suggest that the schedule is feasible in an outpatient setting. Its limited hematological toxicity makes it suitable to be combined with cytotoxic drugs.
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PMID:Home treatment with interleukin 2 and beta-interferon in patients with colorectal cancer and hepatocellular carcinoma. 805 92

The effects of interferon-alpha (IFN-alpha), given at a dosage of 6 MU thrice weekly for 12 months, on gonadal function were investigated in 18 males affected by chronic hepatitis C. Periodically, all patients were clinically monitored and questioned about sexual function. Gonadotropin and serum androgen concentrations (follicle-stimulating hormone, luteinizing hormone, total testosterone, free testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and sex hormone binding globulin) were tested every 3 months. Ten of 18 patients (55%) responded to IFN-alpha therapy. Serum total testosterone and sex hormone binding globulin values decreased slightly at the third month of treatment, then returned to baseline values. Serum free testosterone and other sex hormones remained essentially unchanged during IFN-alpha therapy. Four patients (22.2%) complained of sexual dysfunction (impaired libido, erectile failure, and impaired ejaculation), which was unrelated to any significant hormonal change and resolved after IFN therapy was stopped. Serum sex hormones values did not differ between responders and nonresponders to IFN-alpha. This study indicates that 12 months treatment with 6 MU of IFN-alpha thrice weekly does not significantly affect gonadal function in men with chronic hepatitis C. The sexual dysfunction observed could be ascribed to such other side effects of IFN as asthenia, fatigue, or anxiety, or it could have a psychologic basis.
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PMID:Long-term interferon-alpha therapy does not affect sex hormones in males with chronic hepatitis C. 933 29

Management of advanced malignant mesothelioma (MM) still requires innovative systemic therapy as its prognosis is poorly affected by currently available chemotherapy. The combination cisplatin and alpha-interferon (alpha-INF) has synergistic antitumoral activity in preclinical models and interesting activity in phase I-II clinical trials. Weekly CDDP (60 mg/m2) and alpha-IFN (3 MUI/d: d1-d4) in combination was tested in a previous phase I-II study in 23 MM patients, with a 36% objective response rate (ORR). A trial with higher doses of alpha-IFN in the same combination schedule was conducted to explore an incrementalist hypothesis. Thirty patients with MM received the same CDDP dose (60 mg/m2/w) and doubled doses of alpha-IFN (6 MUI/d: d1-d4). The treatment protocol consisted of two cycles of 4 weeks on/4 weeks off followed by two shorter cycles of 3 weeks on/3 weeks off, in the absence of life-threatening toxicity or progressive disease. All patients were evaluable for toxicity. The main treatment-limiting side-effects were digestive intolerance (nausea, vomiting) and severe asthenia. Antitumoral efficacy was not increased (ORR = 27%). Haematological and neurological toxicities were moderate and manageable. The antitumoral activity of the CDDP-alpha-IFN combination with higher doses of the latter is similar to our previous experience, but tolerance issues make it a poorer choice for eventual comparative trials, or as a standard therapeutic indication.
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PMID:Higher doses of alpha-interferon do not increase the activity of the weekly cisplatin-interferon combination in advanced malignant mesothelioma. 947 Aug 55

Rituximab and IFN have each demonstrated single-agent activity in patients with low-grade non-Hodgkin's lymphoma (NHL). A single-arm, multicenter, Phase II trial was conducted to assess the safety and efficacy of combination therapy with rituximab and IFN-alpha-2a in 38 patients with relapsed or refractory, low-grade or follicular, B-cell NHL. IFN-alpha-2a [2.5 or 5 million units (MIU)] was administered s.c., three times weekly for 12 weeks. Starting on the fifth week of treatment, rituximab was administered by i.v. infusion (375 mg/m2) weekly for 4 doses. All 38 patients received four complete infusions of rituximab and were evaluable for efficacy, although 11 patients (29%) did not-receive all 36 injections of IFN. The mean number of IFN-alpha-2a injections was 31 doses; the mean total units received were 141 MIU (maximum, 180 MIU). The study treatment was reasonably well tolerated with no unexpected toxicities stemming from the combination therapy. No grade 4 events were reported. Frequent adverse events during the treatment period included asthenia (35 of 38 patients), chills (31 of 38), fever (30 of 38), headache (28 of 38), nausea (23 of 38), and myalgia (22 of 38). The overall response rate was 45% (17 of 38 patients); 11% had a complete response, and 34% had a partial response. The Kaplan-Meier estimates for the median response duration and the median time to progression in responders are 22.3 and 25.2 months, respectively. Further follow-up is needed to determine whether this treatment combination leads to a significantly longer time to progression than single-agent treatment with rituximab.
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PMID:Combination immunotherapy of relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma with rituximab and interferon-alpha-2a. 1091 5


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