Phase II trial of monoamine oxidase inhibitor phenelzine in biochemical recurrent prostate cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 94-94 ◽  
Author(s):  
Mitchell E. Gross ◽  
David B. Agus ◽  
Tanya B. Dorff ◽  
Jacek K. Pinski ◽  
David I. Quinn ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Monoamine Oxidase ◽  
Monoamine Oxidase Inhibitor ◽  
Depression Score ◽  
Oxidase Inhibitor ◽  
Monoamine Oxidase A ◽  
Recurrent Prostate Cancer ◽  
Open Label ◽  
Grade 3

94 Background: Monoamine oxidase A (MAOA) influences prostate cancer growth and metastasis in pre-clinical models. We examined effects of phenelzine (a monoamine oxidase inhibitor) in patients with biochemical recurrent castrate-sensitive prostate cancer. Methods: An open-label single arm clinical trial enrolled subjects with biochemical recurrent prostate cancer defined by: PSA ≥ 0.4 ng/ml (post-prostatectomy) or PSA ≥ 2 ng/ml above nadir (post-radiation therapy); no evidence of metastasis on imaging; and normal androgen levels. Subjects received phenelzine 30 mg orally twice daily. Mood symptoms were assessed with the hospital anxiety depression score (HADS) questionnaire. The primary endpoint was the proportion of patients who achieved a PSA decline of ≥50% from baseline. Results: Characteristics of the 20 eligible patients enrolled included: mean ± SD age 66.9 ± 4.8 years and PSA 4.7 ± 5.8 ng/dl. Maximal PSA declines ≥ 30% and ≥ 50% were observed in 25% (n=5/20) and 10% (n=2/20) of subjects, respectively. At 12 weeks, 17 subjects remained on treatment with PSA declines ≥ 30% and ≥ 50% of 24% (n=4/17) and 6% (n=1/17), respectively. Common toxicities observed included dizziness (grade 1 = 45%, grade 2= 35%), hypertension (grade ≥ 2 =30%), and edema (grade 1=25%, grade 2=10%). There was 1 episode of grade 4 hypertension (cycle 4) and 2 episodes of grade 3 syncope (cycle 12 and cycle 14) requiring treatment discontinuation. HADS questionnaires demonstrated a significant decrease in anxiety with no change in depressive symptoms on treatment. Conclusions: Phenelzine demonstrated efficacy in patients with biochemical recurrent castrate sensitive prostate cancer. Most treatment related toxicities were mild, but rare significant and reversible cardiovascular toxicities were observed. Therapies directed at MAOA may represent a new avenue for treatment in patients with recurrent prostate cancer. Clinical trial information: NCT02217709.

Tyramine and New Monoamine Oxidase Inhibitor Drugs

1989 ◽  
Vol 155 (S6) ◽  
pp. 32-37 ◽  
Author(s):  
G.M. Simpson ◽  
J. de Leon
Keyword(s):  
Monoamine Oxidase ◽  
Tricyclic Antidepressants ◽  
Monoamine Oxidase Inhibitor ◽  
Relative Effectiveness ◽  
Hypertensive Crisis ◽  
Oxidase Inhibitor ◽  
Monoamine Oxidase A ◽  
Pressor Test ◽  
The World ◽  
Tyramine Pressor Test

The hypertensive crisis induced by the ingestion of cheese in subjects undergoing treatment with monoamine oxidase inhibitors (MAOIs) led to their virtual disappearance in many parts of the world. Three strategies to try and diminish the risk of this reaction have been developed: the combination of current (irreversible and non-selective) MAOIs with tricyclic antidepressants, the use of new selective MAOIs, and the use of new reversible MAOIs. The relative effectiveness of these different approaches can be assessed by the tyramine pressor test. The introduction of reversible and selective monoamine oxidase-A (MAO-A) inhibitors looks especially promising clinically.

Clinical Trial of Mebanazine—A New Monoamine Oxidase Inhibitor

1965 ◽  
Vol 111 (478) ◽  
pp. 899-902 ◽  
Author(s):  
S. J. G. Gilmour
Keyword(s):  
Clinical Trial ◽  
Side Effects ◽  
Monoamine Oxidase ◽  
Relapse Rate ◽  
Monoamine Oxidase Inhibitor ◽  
Oxidase Inhibitor ◽  
Monoamine Oxidase Inhibitors ◽  
Clinical Use ◽  
Clinical Toxicity

At the time when this investigation was being considered (June, 1961) the efficacy of the monoamine oxidase inhibitors in the treatment of depressive illnesses was already well recognized. It was also evident from a study of the published papers on this group of drugs that their use was accompanied by a number of side-effects which often raised problems in treatment. The clinical trial of a new drug of this class which, from the pre-clinical toxicity studies in animals, held promise of being less toxic than M.A.O. inhibitors already in clinical use was therefore considered worth while. Such a trial also seemed a useful opportunity to follow up previous observations with phenelzine (Gilmour, 1960) and the suggestion of Sargant (1961) that, given concurrently, M.A.O. inhibitors may potentiate the effect of E.C.T. and reduce the number of exposures necessary, and that their continuance after a course of E.C.T. has been completed may reduce the relapse rate.

The clinical relevance of treatment with antidepressants

1995 ◽  
Vol 7 (2) ◽  
pp. 52-54 ◽  
Author(s):  
W.A. Nolen
Keyword(s):  
Monoamine Oxidase ◽  
Clinical Relevance ◽  
Rating Scales ◽  
Monoamine Oxidase Inhibitor ◽  
Oxidase Inhibitor ◽  
Tricyclic Antidepressant ◽  
Statistical Evidence ◽  
Monoamine Oxidase A ◽  
Selective Serotonin ◽  
Uptake Inhibitors

Oince the discovery in the late 1950's of imipramine (Tofranil®), the first tricyclic antidepressant (TCA), and iproniazid, the first monoamine oxidase inhibitor (MAOI), many other TCAs and MAOIs, now being considered the classical antidepressants, have become available. Their effectiveness has been shown in numerous studies, although according to nowadays standards well designed studies (placebo-controlled, defined diagnostic groups, the use of standardized rating scales) with these compounds are relatively scarce.From the early 1980's the so called modern antidepressants have been introduced: the selective serotonin re-uptake inhibitors (SSRIs), the reversible selective monoamine oxidase-A inhibitors (RIMAs) and a variety of other compounds. All these drugs have been registered after their effectiveness had been shown in well designed, placebo-controlled studies. In defining the efficacy of antidepressants, registration authorities consider two aspects important: statistical evidence and clinical relevance.

A clinical trial for the safety and immunogenicity of a DNA-based immunotherapy in men with biochemically (PSA) relapsed prostate cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14634-e14634 ◽  
Author(s):  
Neal D. Shore ◽  
Elisabeth I. Heath ◽  
Luke T. Nordquist ◽  
Heather H. Cheng ◽  
Kamalnayan Bhatt ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Disease Progression ◽  
Open Label ◽  
Median Serum ◽  
Definitive Therapy ◽  
Grade 3 ◽  
Ecog Ps ◽  
Dose Levels ◽  
Site Pain

e14634 Background: Introducing amino acid sequence changes in highly expressed self-antigens for prostate cancer (PCa) patients (pts) might lead to avoidance of immune tolerance. We evaluated a DNA vaccine (INO-5150) including SynCon PSA and PSMA. Administration of INO-5150 to PCa pts along with plasmid encoded adjuvant IL-12 (INO-9012) via electroporation (EP) is postulated to break tolerance, resulting in antigen-specific immune responses which could lead to stabilization of disease progression. Methods: Phase I, open-label, multicenter study of PCa pts post-definitive therapy with a rising PSA ≥ 1.0 ng/ml after surgery, or ≥ 2.0 ng/ml above nadir after RT and PSADT > 3 months, testosterone > 150 ng/dL, no concomitant androgen deprivation therapy and no evidence of metastases within 12 months. We evaluated safety, tolerability and for efficacy signals. INO-5150 low (2 mg, arms A and C) or high (8.5 mg, arms B and D) dose with or without INO-9012 (1 mg) was administered IM followed by EP in total 4 dosing arms on Day 0 and at Wks 3, 12, and 24 in 60 planned pts (15/arm). Pts were followed for 72 Wks. Results: 62 pts, 16 each in arms A and D and 15 in B and C were enrolled. Median age: 69.5 yrs (range 55.4-87.7), Gleason score: 7 (5-10), time from initial diagnosis: 8.2 yrs (0.5-23.8) and ECOG PS: 0 (0-1). As of data cutoff of 23Jan17, 52 pts had EOT visit, 7 withdrawn from treatment and 6 (10%) reported disease progression, 3 biochemical and 3 radiographic. Median serum PSA at enrollment was 4.6 ng/mL (range 1.2, 113.7) and at EOT was 6.5 ng/mL (0.1, 73.6). Median PSADT at enrollment was 8.7 months (3.1, 218.1) and at EOT it was 3.1 months (-23.1, 100.0). Safety: no reports of Grade 4-5 SAEs. 6 Grade 3 SAEs in 5 pts: presyncope, cardiac disorder, fall, neoplasm, ALT and AST elevation. Grade 1-3 AEs reported in 51 (82%) pts: 12 (75%) in Arm A, 13 (87%) B, 13 (87%) C, and 13 (81%) in D. Common AEs were injection site pain (24/39%), swelling (14/23%), erythema (14/23%), all Grade 1-2. Conclusions: INO-5150 (+) and (-) INO-9012 was generally safe and well-tolerated at all 4 dose levels in this patient population. Preliminary data suggest PSA stabilization in some patients. Immune analyses are ongoing. (NCT02514213) Clinical trial information: NCT02514213.

A clinical trial for the safety and immunogenicity of a DNA-based immunotherapy in men with biochemically (PSA) relapsed prostate cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 80-80 ◽  
Author(s):  
Neal D. Shore ◽  
Elisabeth I. Heath ◽  
Luke T. Nordquist ◽  
Heather H. Cheng ◽  
Kamalnayan Bhatt ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Immunological Response ◽  
High Dose ◽  
Open Label ◽  
Definitive Therapy ◽  
Grade 3 ◽  
Dose Levels ◽  
Site Pain ◽  
Clinical Trial Information

80 Background: Introducing amino acid sequence changes in highly expressed self-antigens for androgen sensitive prostate cancer pts might be sufficient to break tolerance, thus a DNA vaccine was developed using SynCon PSA and PSMA (INO-5150) that share 96.8 and 91.6% sequence identities to these native antigens, respectively. Administration of these antigens to prostate cancer pts along with plasmid encoded adjuvant IL-12 (INO-9012) via electroporation (EP) using the CELLECTRA5P device is postulated to break tolerance, resulting in an antigen-specific immune response which could lead to stabilization of disease progression. Methods: This Phase I, open-label, multicenter study included prostate cancer pts post-definitive therapy with a rising PSA ≥ 1.0 ng/ml after surgery, or ≥ 2.0 ng/ml above nadir after RT and PSA doubling time > 3 months, testosterone > 150 ng/dL and no evidence of metastasis within 12 months. INO-5150 with or without INO-9012 was administered IM followed by EP in 4 arms: low (2 mg) or high dose (8.5 mg) INO-5150 alone or with 1 mg INO-9012 on Day 0 and at week 3, 12, and 24 in 60 planned pts (15 pts/arm). DLT assessments were performed after dosing of the first 3 pts of each arm at Week 4. Results: Enrollment is complete in all 4 arms and at data cut-off (10Oct16), 62 enrolled pts received at least one, 60 pts received 3 and about half, 28 pts (10 in arm A, 8 in B, 7 in C, and 3 in D) received all 4 vaccinations. Safety: there were no DLTs noted. Four pts had five Grade 3 SAEs noted as pre-syncope, cardiac disorder, hospitalization for fall, ALT and AST elevation. No Grade 4-5 AEs were noted. Grade 1-3 treatment-emergent AEs occurred in 50 (81%) pts: 12 (75%) in arm A, 13 (87%) B, 13 (87%) C, and 12 (75%) in D. The most common AEs were injection site pain (24/39%), erythema (13/21%), swelling (12/19%), bruising (10/16%), hyperglycemia (8/13%) and fatigue (6/10%), all Grade 1-2. Assessments of immunological response, PSA kinetics and correlation with clinical outcome are ongoing and will be presented. Conclusions: INO-5150 (+) or (-) INO-9012 is generally safe and well-tolerable at all 4 dose levels in a biochemically relapsed prostate cancer patient population. Clinical trial information: NCT02514213.

Bicalutamide with or without metformin for biochemical recurrence in prostate cancer patients (BIMET-1).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 85-85
Author(s):  
Marijo Bilusic ◽  
Matthew R. Zibelman ◽  
Pooja Ghatalia ◽  
Susan Wroblewski ◽  
Ravi Amrit Madan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Total Duration ◽  
Epidemiological Studies ◽  
Primary Objective ◽  
Duration Of Treatment ◽  
Open Label ◽  
Carcinogenic Agent ◽  
Randomized Phase Ii ◽  
Grade 3

85 Background: Metformin (MET) may play a role as an anti-proliferative and anti-carcinogenic agent. Epidemiological studies have demonstrated that MET is associated with decreased prostate cancer (PCa) incidence, including decreased PCa specific mortality in diabetic men with PCa. Preclinical studies have shown synergistic effect of MET with bicalutamide, thus prompting this clinical trial evaluating the combination (NCT02614859). Methods: This was an open label, randomized, phase II trial of pts with biochemically recurrent PCa, PSA doubling time 3-9 months, normal testosterone, and BMI > 25. Pts were randomized (2:1) either to MET 1000 mg twice daily orally or observation for initial 8 weeks. Bicalutamide 50 mg orally daily was added to both arms after 8 weeks. Total duration of treatment was 32 weeks. The primary objective was to determine number of pts with undetectable PSA ( < 0.2 ng/mL) at the end of study with key secondary objectives of evaluating PSA declines of ≥ 85%, PSA responses to MET alone and safety. An early stopping rule for futility was set at 39 pts, but due to slow accrual, an unplanned interim analysis was undertaken. Results: 28 patients were randomized between December 2015 and September 2019. Treatment was well tolerated with no dose reductions or treatment discontinuation. No Grade 3 treatment-related adverse events were observed. Conclusions: PSA responses were seen in 50% pts with MET monotherapy after 8 weeks. Although well tolerated, there was no difference in PSA at 32 weeks between the two arms. The trial will be stopped early due to poor accrual and inability to achieve its primary endpoint. Ongoing larger studies of MET in PCa (STAMPEDE) will define it’s utility in prostate cancer. Clinical trial information: NCT02614859. [Table: see text]

scholarly journals Isolation and Identification of Phenylethanoid Glycosides from Aloysia polystachya and Its Activity as Inhibitors of Monoamine Oxidase-A

2019 ◽  
Vol 6 (01) ◽  
pp. e1-e6 ◽  
Author(s):  
Ana Pereira ◽  
Camila Guimarães ◽  
Sarazete Pereira ◽  
Eduardo Crevelin ◽  
Gustavo Pinto ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Monoamine Oxidase Inhibitor ◽  
Oxidase Inhibitor ◽  
Monoamine Oxidase A ◽  
Indigenous Populations ◽  
Dependent Manner ◽  
Oxidation Reactions ◽  
Phenylethanoid Glycosides ◽  
Isolation And Identification ◽  
Hydroethanolic Extract

Abstract Aloysia polystachya is used as a sedative and antidepressant by the indigenous populations of Argentina and Paraguay, but the compounds associated with these activities have not been determined. We have separated and identified the main constituents of the hydroethanolic extract of A. polystachya by ultra-performance liquid chromatography-mass spectrometry and confirmed the presence of acteoside, isoacteoside, 6'-acetylacteoside, and 4’,4’’’,5,5’’-tetrahydroxy-6,6’’,3’’’-trimethoxy-[C7–O–C7’’]-biflavone by NMR spectroscopy. Inhibitory activities of the hydroethanolic extract and purified phenylethanoid glycosides against monoamine oxidase-A were assessed using a standard fluorometric assay. The hydroethanolic extract inhibited monoamine oxidase-A activity in a dose-dependent manner with an IC50 of 9.2 µg/mL, while the selective monoamine oxidase inhibitor clorgyline exhibited an IC50 of 0.06 µg/mL (0.22 µM). Acteoside was the strongest inhibitor of monoamine oxidase-A (IC50 value of 5 µM), whereas isoacteoside and 6'-acetylacteoside showed IC50 values of around 10 µM. The results showed that phenylethanoids from a hydroethanolic extract of A. polystachya have been found to have inhibitory activity against monoamine oxidase-A. It is likely that the mode of action of the acteosides is multi-targeted, involving the downregulation of inflammatory molecules and neutralization of oxidation reactions as well as inhibition of monoamine oxidase-A.

An Australian Multicentre Study of Moclobemide versus Amitriptyline in the Treatment of Depression

1992 ◽  
Vol 26 (3) ◽  
pp. 454-458 ◽  
Author(s):  
Larry Evans ◽  
Tom George ◽  
Brendan O'sullivan ◽  
Philip Mitchell ◽  
Gordon Johnson ◽  
...  
Keyword(s):  
Major Depression ◽  
Monoamine Oxidase ◽  
Multicentre Study ◽  
Monoamine Oxidase Inhibitor ◽  
Oxidase Inhibitor ◽  
Monoamine Oxidase A ◽  
Double Blind ◽  
Blood Pressure Elevation ◽  
Treatment Of Depression ◽  
Blind Comparison

This paper reports the results of a multicentre study of the new monoamine oxidase inhibitor, moclobemide, in the treatment of major depression. Moclobemide is a specific monoamine oxidase-A inhibitor which does not bind irreversibly to the enzyme, unlike the currently available MAOIs. Recent studies would suggest that in subjects taking moclobemide blood pressure elevation caused by tyramine is significantly less than that induced by the irreversible MAOIs, particularly when tyramine is administered in an oral form. Forty-eight patients with major depression were randomly allocated to treatment with either moclobemide or amitriptyline for 4 weeks in a double-blind comparison. There were no statistically significant differences between the two groups on measures of efficacy. Patients taking amitriptyline reported a greater number of side-effects and more patients in the amitriptyline group dropped out because of these. There were no reports of interactions with tyramine-containing foods.

Controlled Clinical Trial of Isocarboxazid (“Marplan”) in Hospital Psychiatry

1961 ◽  
Vol 107 (448) ◽  
pp. 567-571 ◽  
Author(s):  
Vasant G. Joshi
Keyword(s):  
Clinical Trial ◽  
Monoamine Oxidase ◽  
Monoamine Oxidase Inhibitor ◽  
Oxidase Inhibitor ◽  
Controlled Clinical Trial ◽  
Synthetic Drugs ◽  
Uncontrolled Trial ◽  
Treatment Of Depression ◽  
Hospital Psychiatry

A number of synthetic drugs have recently been introduced as specific antidepressants in psychiatry. Isocarboxazid (Marplan) is an analogue of iproniazid (Marsilid). Both belong to the monoamine oxidase inhibitor group of antidepressants. Isocarboxazid is said to be less toxic but of equal potency for a lesser dose than iproniazid. A controlled clinical trial of isocarboxazid was therefore undertaken to assess this drug in the treatment of depression. The results of this trial are reported in this paper together with the results of an uncontrolled trial in a further group of patients (group M) who received isocarboxazid only.

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