72715
document
Randomized trial of recombinant alpha 2b-interferon with or without indomethacin in patients with metastatic malignant melanoma . alpha-Interferon has antitumor activity in a variety of malignancies but is frequently associated with unacceptable toxic side-effects . The routine use of agents potentially capable of reducing these side-effects has not been recommended out of concern for possible reductions in the therapeutic activity of interferon . We conducted a prospective randomized trial of alpha-interferon given with or without indomethacin to patients with malignant melanoma to determine what effect , if any , indomethacin might have on the toxic , immunomodulatory , and therapeutic properties of interferon in this disease . 53 patients were stratified according to performance status and randomized to receive alpha 2b-interferon , 20 million units per m2 i.v. , 5 days per week for 4 weeks followed by 10 million units per m2 s.c. three times per week , either with or without indomethacin , 25 mg orally three times a day . The overall major response rate was 13 % ( three complete responders and three partial responders among 47 evaluable patients ) and was the same on both arms . The mean maximal temperature elevation induced by interferon was significantly reduced ( from 102.1 to 100.7 , P = 0.0002 ) by indomethacin , but the incidence and severity of interferon-related fatigue , reduction in performance status , headache , depression , confusion , elevations in liver function tests , and myelosuppression were no different in either arm of the study . Indomethacin did not reduce the frequency of dose reductions for toxic side-effects and did not permit the administration of higher interferon doses . Peripheral blood natural killer activity was significantly enhanced in patients during maintenance therapy whether or not they received indomethacin . Indomethacin appeared to inhibit augmentation of natural killer activity during high dose induction therapy . Immunological changes did not correlate with response status . We conclude that indomethacin can reduce the fever associated with interferon therapy in patients with malignant melanoma without interfering with its therapeutic or chronic immunomodulatory activities . Since fever is rarely the dose-limiting toxicity of interferon , indomethacin is of marginal benefit to patients with malignant melanoma receiving interferon at the doses outlined in this study .
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Intervention_Pharmacological
recombinant alpha 2b-interferon
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Intervention_Pharmacological
indomethacin
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Intervention_Pharmacological
alpha-Interferon
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Intervention_Pharmacological
indomethacin
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Intervention_Pharmacological
indomethacin
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Intervention_Pharmacological
alpha 2b-interferon
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Intervention_Pharmacological
indomethacin
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Intervention_Pharmacological
indomethacin
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Intervention_Pharmacological
Indomethacin
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Intervention_Pharmacological
Indomethacin
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Intervention_Pharmacological
indomethacin
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Outcome_Adverse-effects
toxic side-effects
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Outcome_Adverse-effects
toxic
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Outcome_Other
immunomodulatory
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Outcome_Other
therapeutic properties
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Outcome_Other
overall major
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Outcome_Physical
response rate
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Outcome_Physical
mean maximal temperature elevation
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Outcome_Physical
incidence and severity of interferon-related fatigue
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Outcome_Physical
reduction in performance status
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Outcome_Physical
headache
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Outcome_Mental
depression
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Outcome_Mental
confusion
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Outcome_Physical
elevations in liver function tests
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Outcome_Physical
myelosuppression
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Outcome_Adverse-effects
frequency of dose reductions for toxic side-effects
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Outcome_Other
administration of higher interferon doses
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Outcome_Physical
Peripheral blood natural killer activity
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Outcome_Physical
augmentation of natural killer activity
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Outcome_Physical
Immunological changes
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Outcome_Physical
fever
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Outcome_Physical
therapeutic or chronic immunomodulatory activities
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Outcome_Physical
fever
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Participant_Condition
metastatic malignant melanoma
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Participant_Condition
malignant melanoma
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Participant_Sample-size
53
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Participant_Condition
malignant melanoma
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Participant_Condition
malignant melanoma