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)

The role of combination chemotherapy in the treatment of advanced non-small-cell lung cancer is controversial. At best, a small survival benefit can be achieved. Therefore, other treatment modalities are needed. On the basis of the promising treatment results with interleukin-2 (IL-2) -containing immunotherapy in renal cell cancer and melanoma, we performed a phase I-II study with IL-2 and interferon alpha (IFN-alpha). Eligible patients were treated with IL-2 18 x 10(6) IU/m2/day by continuous intravenous infusion (c.i.v.) for 3 days. On the same days, 5 x 10(6) U/m2/day IFN-alpha was given intramuscularly. After a rest period of 4 days, patients at the first dose level received IL-2 2.4 x 10(6) IU/m2/day c.i.v. for a period of 28 days, followed by 14 days' rest, 14 days' treatment, 7 days' rest, and a final treatment for 14 days. Patients at the second dose level were treated according to the same schedule, in which the dose of IL-2 was increased to 3.6 x 10(6) IU/m2/day. During low-dose IL-2 treatment, patients received IFN-alpha 5 x 10(6) U/m2/day on days 1 and 4 of each week. Eleven patients were admitted to the study, six at the first and five at the second dose level. Median age was 54 years; all patients had a performance status of 0 or 1. The most important adverse effects included anorexia, fatigue, nausea, and headache, which were not dose limiting. In the 11 patients treated, no responses were seen. Nine patients developed progressive disease during the first 5 weeks of treatment. We concluded that this regimen of IL-2 and IFN-alpha is ineffective.
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PMID:Interleukin-2 and interferon-alpha in the treatment of patients with advanced non-small-cell lung cancer. 132 67

Based on recent preclinical data suggesting synergism between 5-fluorouracil (5-FU) and interferon alpha (IFN-alpha) and clinical activity of the combination therapy in colon cancer, 14 patients with advanced gastric cancer were treated with combination therapy of 5-FU and recombinant interferon alpha-2b (rIFN alpha-2b) (Intron A, Schering, Kenilworth, NJ, U.S.A.). The maximum tolerated dose was 5-FU 750 mg/m2/day given as a continuous infusion daily for 5 days followed by weekly bolus injection of the same initial daily dose, plus rIFN alpha-2b 5 X 10(6) U given subcutaneously 3 times weekly starting day 1 of 5-FU infusion. The dose-limiting toxicities were fatigue/weakness, diarrhea, and neurologic toxicities such as somnolence and confusion. The other common side effects were nausea, fever, leukocytopenia, thrombocytopenia, and the darkening of the skin. Of 13 evaluable patients, 4 had a partial response (duration 6, 14, 24, and 28 weeks). These data suggest that combination therapy of 5-FU plus rIFN alpha-2b is tolerable and has manageable side effects in patients with advanced gastric cancer. Further Phase II study will be needed to define the antitumor activity of this combination.
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PMID:Combination of 5-fluorouracil and recombinant interferon alpha-2B in advanced gastric cancer. A phase I study. 155 2

Kaposi's sarcoma (KS) is a malignant neoplasm that develops in 20% to 30% of all acquired immunodeficiency syndrome (AIDS) cases. Kaposi's sarcoma primarily involves the skin, but can progress to involve the lungs, gastrointestinal tract, and liver. alpha-Interferon alone or in combination with zivoduvine has activity in acquired immunodeficiency syndrome-related KS, especially in patients with limited disease and CD4 lymphocyte counts over 400/mm3. Patients with progressive or symptomatic visceral disease, however, can be treated more effectively with cytotoxic chemotherapy. We have used a combination of doxorubicin, bleomycin, and vincristine (ABV) and have achieved response rates of over 80%. Discontinuation of therapy, however, is associated with relapse shortly after response (2 to 3 months). Thus, we have begun studies to define a safe and effective maintenance therapy. Such therapies should include antiretroviral agents since most patients succumb to other human immunodeficiency virus complications, and since human immunodeficiency virus directly, through viral proteins, and indirectly, through the induction of cellular genes, induces KS growth. Additionally, agents with antitumor activity and possible antiviral activity, such as alpha-interferon, may be potentially effective in maintenance therapies. We recently studied 21 patients in a phase I study of recombinant interferon alpha-2b (INTRON-A, Schering-Plough Corp, Kenilworth, NJ) alone following ABV chemotherapy. A dose of 10 million units, given in daily subcutaneous injections, was the maximal tolerated dose; higher doses were associated with intolerable fatigue, diarrhea, and fevers. We are currently conducting a phase I/II trial studying the combination of zivoduvine (500 mg/d) and recombinant interferon alpha-2b (5, 10, and 15 million units) as maintenance in patients with advanced or progressive KS.
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PMID:Phase I/II trials of alpha-interferon alone or in combination with zidovudine as maintenance therapy following induction chemotherapy in the treatment of acquired immunodeficiency syndrome-related Kaposi's sarcoma. 171 42

Malignant carcinoid tumours with the carcinoid syndrome has over the years presented a therapeutic challenge. The patients might not only die from tumour progression but also from symptoms relating to hormone overproduction and the specific cardiac disease, e.g. right heart fibrosis and failure. Surgery has been the treatment of choice in local disease, but when liver metastases have developed other treatment procedures must be considered. Conventional chemotherapy has been of little beneficial value, with response rates of only 10-30%, whereas a new somatostatin analogue, octreotid, is effective in controlling clinical symptoms but not tumour progression. Interferon treatment was introduced in 1982 by our group, and we are now presenting treatment results of 130 patients with histologically verified malignant carcinoid tumours and liver metastases. One hundred and eleven patients were treated with a median dose of 6 mega units (MU) of interferon alpha, five times weekly (dose range 3-9 MU), whereas 29 patients received conventional chemotherapy. Forty-seven out of 111 patients (42%) treated with interferon alpha demonstrated a significant biochemical response and 15% demonstrated more than 50% reduction in tumour size. In another 43 (39%) patients stabilization of the carcinoid disease have been noted, whereas 21 (19%) showed progressive disease. The median duration of response was 34 months. Subjective responses with improvement of diarrhoea, flush and/or bronchoconstriction were noticed in 76 patients (68%). The 19 patients treated with chemotherapy demonstrated only 10% biochemical response, lasting for only 3-5 months. The survival analysis demonstrates a median survival of only 8 months in the group of patients treated with chemotherapy, compared to 80+ months (P less than 0.001) in the groups treated with interferon alpha. Interferon adverse reactions of fatigue, weight loss and anaemia were manageable. Neutralizing interferon antibodies were documented in 5-15% of the patients. Interferon alphas are active in patients with malignant carcinoid tumours. Clinical symptoms are significantly reduced following reduction of circulating hormones. Interferon might also have an impact on survival in this group of patients. The side-effects are moderate and managed by dose adjustments.
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PMID:The role of interferons in the management of carcinoid tumours. 183 59

Fourteen patients with metastatic carcinoid tumors were treated with recombinant interferon alpha-2b at a dosage of 3-4 x 10(6) IU s.c. daily or every second day. No objective tumor regression was observed. Six out of 8 patients with carcinoids of the ileum and the caecum showed stable disease lasting for a median of 25 months (range 4-57). In 3 out of 6 patients with carcinoids of rectum, lung and of unknown primary site, stable disease was observed lasting for 2-7 months. The remaining patients had progressive disease. Six out of 9 evaluable patients had a more than 50% reduction of urinary 24 h 5-hydroxyindoleacetic acid excretion lasting for a median of 4 months (range 2-11). Decrease of flushing was noticed in 3 out of 6 evaluable patients and decrease of diarrhea in 5 out of 9 evaluable patients. In 4 patients dose reduction was necessary due to confusion and fatigue.
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PMID:Treatment of metastatic carcinoid tumors and the carcinoid syndrome with recombinant interferon alpha. 189 78

In a randomized study of advanced renal cell carcinoma 60 patients were allocated to treatment with either recombinant interferon alpha-2a or medroxyprogesterone acetate. Correlation between the dose of interferon alpha-2a and plasma-concentration indicated linear kinetics. Survival was similar in the two treatment groups. Only one complete and one partial response were seen in the interferon group and only one complete response in the medroxyprogesterone group, indicating a low therapeutic potential of both interferon and medroxyprogesterone. Interferon influenced the serum liver enzyme levels; increased transaminases were seen in 17 patients treated with interferon but in only four patients in the medroxyprogesterone group. Two patients had very high serum liver-enzyme levels concomitant with intolerable tiredness, in both patients the symptoms disappeared and the enzymes normalized after discontinuation of the interferon treatment. Antibodies to interferon developed frequently in patients receiving high dose oligomeric interferon therapy but rarely in patients receiving low dose monomeric interferon treatment.
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PMID:Recombinant leukocyte interferon alpha-2a and medroxyprogesterone in advanced renal cell carcinoma. A randomized trial. 218 3

Based on the report of some activity of combination therapy with dacarbazine (DTIC) and interferon alpha-2a (rIFN alpha-2a) in disseminated melanoma, we conducted a phase II study to determine the feasibility and efficacy in a large series of patients. DTIC was administered in 79 patients at the dose of 800 mg/m2 every 3 weeks and rIFN alpha-2a was given daily at the dose of 9 X 10(6) IU for the first 10 weeks and three times a week thereafter. Among the 75 evaluable patients, 25% achieved an objective response, with 8% complete and 17% partial remissions. The regression occurred within a mean time of 1.9 +/- 1.03 months from starting therapy and the mean duration of response was 8.2 +/- 4.2 months. The major side effects were vomiting, anorexia, fever, fatigue, and myalgia. There was one death related to sepsis after myelosuppression. In the other patients bone marrow and liver toxicities were not remarkable. Our data reveal that a combination regimen of rIFN alpha-2a with a cytotoxic agent has some therapeutic activity in the management of advanced malignant melanoma.
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PMID:Phase II study of interferon alpha-2a and dacarbazine in advanced melanoma. 222 Jun 60

A pilot study was undertaken to evaluate toxicity and activity of recombinant alpha-2b interferon in patients with metastatic malignant melanoma. Interferon was administered at the dosage of 10 x 10(6) IU/m2, 3 times a week i.m. 21 patients entered the study, 17 pretreated with chemotherapy and/or immunotherapy and 6 untreated. We obtained 3 partial responses (14.3%; 95% CL, 3.0-36.3%); 9 patients had stable disease. All patients experienced flue-like symptoms and fever; most fatigue and worsening of performance status. Recombinant interferon alpha-2b at the dosage and schedule used has limited but definite activity in metastatic malignant melanoma; the substantial subjective toxicity must be taken into consideration. Further trials testing recombinant alpha interferon in combination with chemotherapeutic agents, like DTIC, are warranted.
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PMID:Phase II trial of recombinant alpha-2b interferon in the treatment of metastatic skin melanoma. 271 Apr 82

A total of 66 patients with advanced renal cell cancer received a combination of recombinant interferon alpha-2a (18 times 10(6) units subcutaneously 3 times weekly) and vinblastine (0.1 mg. per kg. intravenously every 3 weeks). Four patients were ineligible and 6 were inevaluable for response but evaluable for toxicity. There were no complete and 9 partial responses among the 56 evaluable patients, for a response rate of 16 per cent. Median duration of response was 26 weeks, with a range of 8 to 50 weeks. Responses were observed predominantly in patients with lung and soft tissue metastases. Patients who had undergone nephrectomy did not show a better response rate than those who had not. Almost all patients had a flu-like syndrome, fatigue and anorexia. Other side effects included leukopenia, nausea, vomiting, liver function disturbances and neurotoxicity. Most of the side effects were World Health Organization grade 1 or 2; no grade 4 toxicity was observed. Antibodies against interferon developed in 6 patients during the course of treatment. However, there was no relationship between the appearance of antibodies and disease progression. The combination of recombinant interferon alpha-2a and vinblastine has modest but definite activity in patients with advanced renal cell carcinoma, although the role of vinblastine is unclear.
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PMID:Phase II study of recombinant interferon alpha-2a and vinblastine in advanced renal cell carcinoma. 274 39

Two hundred three patients (median age 26 years; range 18-45) with untreated multiple and widespread anogenital condyloma were randomly assigned to one of four study arms in order to compare the efficacy, toxicity, and tolerability of recombinant interferon alpha-2b with those of diathermocoagulation. Of 200 evaluable patients, 51 were treated intramuscularly (IM) with 3 x 10(6) U (3 MU)/m2 daily for 3 weeks (total dose 63 MU/m2), 50 received subcutaneous thrice-weekly injections of 3 MU/m2 for 4 weeks (total dose 36 MU/m2), 51 underwent diathermocoagulation, and 48 were not treated and were used as a control group. Six months after the end of treatment, the overall response rate (complete and partial responses) was 70%: 57 and 82% for patients receiving interferon alpha-2b (IM and subcutaneously) and diathermocoagulation, respectively, and 8% for the control group. After 6 months from therapy, no significant differences in complete response were found among the different types of treatment: 20, 20, and 35% for the two interferon groups and the diathermocoagulation group, respectively. Fifteen and two complete responders in the cauterization and interferon groups, respectively, experienced disease recurrence (P less than .01). All patients given interferon therapy complained of flu-like symptoms, which declined progressively after the first week of treatment. Fatigue, lasting as long as patients received interferon, was the most prevalent chronic side effect. We conclude that systemic recombinant interferon alpha-2b is active in treating patients with primary condyloma lesions and does so as well as cauterization.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Randomized clinical trial comparing systemic interferon with diathermocoagulation in primary multiple and widespread anogenital condyloma. 276 17


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