460:(MTD)of NAMI-A as well as determining the pharmacokinetics of NAMI-A and gemcitabine administered jointly. This was accomplished by a dose escalation study. The minimal dosage was 300 mg/m on a 28-day schedule and the max dosage was 600 mg/m administered on a 21-day schedule. 32 patients were enrolled in the study all of which had a form of
25:
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Contrary to what can be found in some papers, the nickname NAMI is not the acronym of “New
Anticancer Metastasis Inhibitor”, but has a much more prosaic origin. It was created by a student as a short-form name of the chemical formula of the complex: “NA” comes from the symbol for sodium and “MI” from
472:
Phase II trials were done to evaluate how NAMI-A in combination with gemcitabine impact cancer progression. 19 patients were added in addition to those from the phase I trial. Of the 27 patients evaluated for final results -15 showed anti-tumor activity, 10 showed stable disease progression for 6–10
357:
One trial was done to test the efficacy of NAMI-A in female grafted with MCa mammary carcinoma cells. It was determined that, NAMI-A showed very little toxicity yet managed to decrease the rate of metastasis. Perhaps most impressively is that, though NAMI-A is very sensitive to the environment, it
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The patient who was observed to have a partial remission, occurred during the dose escalation phase I trial. In order to expand the trial, there needed to be at least one patient in the phase II trial that showed PR as the best response. Unfortunately, this did not occur. In addition, it was found
589:
Alessio E, Messori L (2018). "Chapter 5. The
Deceptively Similar Ruthenium(III) Drug Candidates KP1019 and NAMI-A have Different Actions. What Did We Learn in the Past 30 Years?". In Sigel A, Sigel H, Freisinger E, Sigel RK (eds.).
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Leijen S, Burgers SA, Baas P, Pluim D, Tibben M, van
Werkhoven E, et al. (February 2015). "Phase I/II study with ruthenium compound NAMI-A and gemcitabine in patients with non-small cell lung cancer after first line therapy".
545:
Lentz F, Drescher A, Lindauer A, Henke M, Hilger RA, Hartinger CG, et al. (February 2009). "Pharmacokinetics of a novel anticancer ruthenium complex (KP1019, FFC14A) in a phase I dose-escalation study".
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Due to negative results of the stand-alone Phase I trial, and knowledge that NAMI-A slows down progression of metastasis, and not growth of the initial tumor, Phase I & II trials were done using
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Sava G, Bergamo A, Zorzet S, Gava B, Casarsa C, Cocchietto M, et al. (February 2002). "Influence of chemical stability on the activity of the antimetastasis ruthenium compound NAMI-A".
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Phase I trials were conducted on NAMI-A in patients with varying solid tumors 3 hrs a day, 5 days a week, for 3 weeks at varying doses. Drug was given intravenously with and without a
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Of the 24 patients in the study, 20 were evaluated for final results. At the end of the study, 19 of the 20 showed disease progression while 1 patient showed no progression.
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Alessio E, Guo Z (September 28, 2016). "Thirty Years of the Drug
Candidate NAMI-A and the Myths in the Field of Ruthenium Anticancer Compounds: A Personal Perspective".
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the word imidazole. The corresponding imidazolium salt was simply called NAMI-A to signify that it was an upgraded version of the prototype NAMI".
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705:"In vitro cell cycle arrest, in vivo action on solid metastasizing tumors, and host toxicity of the antimetastatic drug NAMI-A and cisplatin"
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that the results of NAMI-A in combination with gemcitabine, did not show improved results from studies done with gemcitabine alone.
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671:"Dual Action of NAMI-A in inhibition of solid tumor metastasis: selective targeting of metastatic cells and binding to collagen"
339:, a platinum based drug, NAMI-A affects metastasis. Whereas platinum compounds can be highly cytotoxic, NAMI-A is much less so.
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incubated with NAMI-A, were not able to proliferate but that NAMI-A did not kill the cells that were already grown.
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739:"Inhibition of endothelial cell functions and of angiogenesis by the metastasis inhibitor NAMI-A"
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Vacca A, Bruno M, Boccarelli A, Coluccia M, Ribatti D, Bergamo A, et al. (March 2002).
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Bergamo A, Gagliardi R, Scarcia V, Furlani A, Alessio E, Mestroni G, Sava G (April 1999).
464:(NSCLC), a median age of 57, most diagnosed as level III & IV of disease progression.
594:. Metal Ions in Life Sciences. Vol. 18. Berlin: de Gruyter GmbH. pp. 141–170.
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increase – common toxicity (CTC) grade 1 and 2 - High levels indicate kidney dysfunction
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Due to these results, Phase II trials, using NAMI-A as a solo drug, were not pursued.
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Sava G, Zorzet S, Turrin C, Vita F, Soranzo M, Zabucchi G, et al. (May 2003).
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Imidazolium-trans-tetrachloro(dimethylsulfoxide)imidazoleruthenium(III)
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320:. At pH 7.4, a chloride is replaced by water giving a charge-neutral
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NAMI-A is considered a pro-drug formulation that becomes active upon
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Several preclinical trials were conducted in various model systems.
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NAMI-A dissociates differently based on pH (Sava et al., 2001).
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Lukashevich IS, Malkovský M, Schorlemmer HU, Bobé P, Artym J.
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Kostova I (2006). "Ruthenium complexes as anticancer agents".
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324:. At lower pH, imidazole is cleaved and replaced with water.
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The
Journal of Pharmacology and Experimental Therapeutics
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Metallo-Drugs:Development and Action of
Anticancer Agents
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that has shown to be successful in treating lung cancer.
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Due to these results, clinical trials were terminated.
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In 2002, a study published by Vacca et al. showed that
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Phase I trials were done to determine the optimal and
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is the imidazolium]] salt of the coordination complex
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Phase I and II – combination therapy with gemcitabine
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is able to be effective over a range of conditions.
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66:Learn how and when to remove this message
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473:weeks, and 1 patient exhibited a
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416:Sensitivity reactions to drug
560:10.1097/CAD.0b013e328322fbc5
368:Netherlands Cancer Institute
296:is imidazole Together with
512:Current Medicinal Chemistry
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636:European Journal of Cancer
524:10.2174/092986706776360941
462:non-small cell lung cancer
425:Blisters on hands and feet
193:Chemical and physical data
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815:Investigational New Drugs
743:British Journal of Cancer
600:10.1515/9783110470734-011
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678:Clinical Cancer Research
957:Ruthenium(IV) compounds
927:DNA-binding substances
880:10.1002/ejic.201600986
755:10.1038/sj.bjc.6600176
458:maximum tolerated dose
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374:Phase I – monotherapy
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36:confusing or unclear
937:Ruthenium complexes
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44:clarify the article
788:"Mice, Inbred CBA"
343:Preclinical trials
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874:(12): 1549–1560.
548:Anti-Cancer Drugs
475:partial remission
446:nucleoside analog
422:at injection site
352:endothelial cells
279:dimethylsulfoxide
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42:Please help
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836:1874/314465
442:gemcitabine
380:port-a-cath
248: g·mol
163:201653-76-1
128:Identifiers
107:Intravenous
947:Sulfoxides
942:Imidazoles
916:Categories
497:References
408:Creatinine
399:Stomatitis
318:hydrolysis
241:Molar mass
183:60487Z56XW
154:CAS Number
137:IUPAC name
56:April 2011
38:to readers
792:WikiGenes
420:Phlebitis
337:cisplatin
312:Reactions
259:[RuCl
101:Routes of
853:27817700
845:25344453
773:11953835
724:10087050
690:12738748
656:11818210
618:29394024
576:38457574
568:19209025
532:16611086
395:Diarrhea
392:Vomiting
302:BOLD-100
263:(dmso)(C
113:ATC code
764:2364145
404:Fatigue
370:(NKI).
335:Unlike
199:Formula
34:may be
907:NAMI-A
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389:Nausea
298:KP1019
255:NAMI-A
246:458.17
80:NAMI-A
849:S2CID
708:(PDF)
674:(PDF)
572:S2CID
413:Fever
872:2017
841:PMID
769:PMID
720:PMID
686:PMID
652:PMID
614:PMID
604:ISBN
564:PMID
528:PMID
444:, a
300:and
281:and
174:UNII
120:None
884:hdl
876:doi
831:hdl
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759:PMC
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231:Ru
216:Cl
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234:S
228:O
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222:N
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210:H
207:8
204:C
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Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
