Phase I/II study with ruthenium compound NAMI-A and gemcitabine in patients with non-small cell lung cancer after first line therapy

Investigational New Drugs

Volumn 33, Issue 1, 2015, Pages 201-214

  Leijen, Suzanne ^a   Burgers, Sjaak A ^a   Baas, Paul ^a,b   Pluim, Dick ^a   Tibben, Matthijs ^c   Van Werkhoven, Erik ^a   Alessio, Enzo ^d   Sava, Gianni ^d,e   Beijnen, Jos H ^c   Schellens, Jan H M ^a,f  

^a NETHERLANDS CANCER INSTITUTE   (Netherlands)

^b ACADEMIC MEDICAL CENTER   (Netherlands)

^c SLOTERVAART HOSPITAL   (Netherlands)

^d UNIVERSITY OF TRIESTE   (Italy)

^e Callerio Foundation   (Italy)

^f UTRECHT UNIVERSITY   (Netherlands)

Author keywords

Clinical study; Gemcitabine; NAMI A; Non small cell lung cancer; Phase I; Phase II; Ruthenium

Indexed keywords

ALANINE AMINOTRANSFERASE; ANTINEOPLASTIC AGENT; ASPARTATE AMINOTRANSFERASE; CREATININE; GEMCITABINE; NOVEL ANTI TUMOR METASTASIS INHIBITOR A; RUTHENIUM DERIVATIVE; UNCLASSIFIED DRUG; DEOXYCYTIDINE; DIMETHYL SULFOXIDE; IMIDAZOLIUM-BIS(IMIDAZOLE)DIMETHYLSULFOXIDEIMIDAZOTETRACHLORORUTHENATE(III); ORGANOMETALLIC COMPOUND; RUTHENIUM;

ADULT; AGED; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALLERGIC REACTION; ANEMIA; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BLISTER; CLINICAL ARTICLE; CONSTIPATION; CONTROLLED STUDY; CREATININE BLOOD LEVEL; DIARRHEA; DOSE LIMITING TOXICITY; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG HALF LIFE; DRUG SAFETY; FATIGUE; FEMALE; FEVER; HUMAN; LEUKOPENIA; MALE; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUROPATHY; NEUTROPENIA; NON SMALL CELL LUNG CANCER; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PLASMA CONCENTRATION-TIME CURVE; PNEUMONIA; PRIORITY JOURNAL; THROMBOCYTOPENIA; THROMBOSIS; TOXICITY; VOMITING; ANALOGS AND DERIVATIVES; BLOOD; CARCINOMA, NON-SMALL-CELL LUNG; CLINICAL TRIAL; LUNG NEOPLASMS; METABOLISM; MIDDLE AGED; TREATMENT OUTCOME;

ADULT; AGED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CARCINOMA, NON-SMALL-CELL LUNG; DEOXYCYTIDINE; DIMETHYL SULFOXIDE; FEMALE; HUMANS; LUNG NEOPLASMS; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; ORGANOMETALLIC COMPOUNDS; RUTHENIUM; TREATMENT OUTCOME;

EID: 84922005327     PISSN: 01676997     EISSN: 15730646     Source Type: Journal    
DOI: 10.1007/s10637-014-0179-1     Document Type: Article

References (67)

1. Brabec V, Kasparkova J (2005) Modifications of DNA by platinum complexes. Relation to resistance of tumors to platinum antitumor drugs. Drug Resist Updat 8:131-146
2. Galanski M, Jakupec MA, Keppler BK (2005) Update of the preclinical situation of anticancer platinum complexes: novel design strategies and innovative analytical approaches. Curr Med Chem 12:2075-2094
3. Galanski M (2006) Recent developments in the field of anticancer platinum complexes. Recent Pat Anticancer Drug Discov 1:285-295
4. Reedijk J (1999) Medicinal applications of heavy-metal compounds. Curr Opin Chem Biol 3:236-240
5. Weiss RB, Christian MC (1993) New cisplatin analogues in development. Rev Drugs 46:360-377
6. Bratsos I, Gianferrara T, Alessio E, Hartinger MA, Jakupec B, Keppler BK (2011) Ruthenium and other non-platinum anti-cancer compounds; in bioinorganic medicinal chemistry., pp 151-174
7. Giraldi T, Sava G (1981) Selective antimetastatic drugs (review). Anticancer Res 1:163-174
8. Ott I, Gust R (2007) Non platinum metal complexes as anti-cancer drugs. Arch Pharm (Weinheim) 340:117-126
9. Alessio E, Mestroni G, Bergamo A, Sava G (2004) Ruthenium anticancer drugs. Met Ions Biol Syst 42:323-351
10. Sava G, Pacor S, Mestroni G, Alessio E (1992) Na[trans-RuCl4(DMSO)Im], a metal complex of ruthenium with antimetastatic properties. Clin Exp Metastasis 10:273-280
11. Sava G, Bergamo A (1999) Drug control of solid tumour metastases: a critical view. Anticancer Res 19:1117-1124
12. Frasca D, Ciampa J, Emerson J, Umans RS, Clarke MJ (1996) Effects of hypoxia and transferrin on toxicity and DNA binding of ruthenium antitumor agents in hela cells. Metal-Based Drugs 3:197-209
13. Clarke MJ (2002) Ruthenium metallopharmaceuticals. Coord Chem Rev 232:69-93
14. Messori L, Vilchez FG, Vilaplana R, Piccioli F, Alessio E, Keppler B (2000) Binding of antitumor ruthenium(III) complexes to plasma proteins. Metal-Based Drugs 7:335-342
15. Messori L, Orioli P, Vullo D, Alessio E, Iengo E (2000) A spectroscopic study of the reaction of NAMI, a novel ruthenium(III)anti-neoplastic complex, with bovine serum albumin. Eur J Biochem 267:1206-1213
16. Allardyce CS, Dyson PJ (2001) Ruthenium in medicine: current clinical uses and future prospects. Platin Met Rev 45:62-69
17. Clarke MJ, Zhu F, Frasca DR (1999) Non-platinum chemotherapeutic metallopharmaceuticals. Chem Rev 99:2511-2534
18. Clarke MJ, Bitler S, Rennert D, Buchbinder M, Kelman AD (1980) Reduction and subsequent binding of ruthenium ions catalyzed by subcellular components. J Inorg Biochem 12:79-87
19. Antonarakis ES, Emadi A (2010) Ruthenium-based chemotherapeutics: are they ready for prime time? Cancer Chemother Pharmacol 66:1-9
20. Bloemink MJ, Reedijk J (1996) Cisplatin and derived anticancer drugs: mechanism and current status of DNA binding. Met Ions Biol Syst 32:641-685
21. Reedijk J (2003) New clues for platinum antitumor chemistry: kinetically controlled metal binding to DNA. Proc Natl Acad Sci U S A 100:3611-3616
22. Bergamo A, Sava G (2011) Ruthenium anticancer compounds: myths and realities of the emerging metal-based drugs. Dalton Trans 40:7817-7823
23. Bergamo A, Gaiddon C, Schellens JH, Beijnen JH, Sava G (2012) Approaching tumour therapy beyond platinum drugs: status of the art and perspectives of ruthenium drug candidates. J Inorg Biochem 106:90-99
24. Kostova I (2006) Ruthenium complexes as anticancer agents. Curr Med Chem 13:1085-1107
25. Rademaker-Lakhai JM, van den Bongard D, Pluim D, Beijnen JH, Schellens JH (2004) A Phase I and pharmacological study with imidazolium-trans-DMSO-imidazole-tetrachlororuthenate, a novel ruthenium anticancer agent. Clin Cancer Res 10:3717-3727
26. Frausin F, Scarcia V, Cocchietto M, Furlani A, Serli B, Alessio E, Sava G (2005) Free exchange across cells, and echistatin-sensitive membrane target for the metastasis inhibitor NAMI-A (imidazolium trans-imidazole dimethyl sulfoxide tetrachlororuthenate) on KB tumor cells. J Pharmacol Exp Ther 313:227-233
27. Sava G, Frausin F, Cocchietto M, Vita F, Podda E, Spessotto P, Furlani A, Scarcia V, Zabucchi G (2004) Actin-dependent tumour cell adhesion after short-term exposure to the antimetastasis ruthenium complex NAMI-A. Eur J Cancer 40:1383-1396
28. Bergamo A, Sava G (2007) Ruthenium complexes can target determinants of tumour malignancy. Dalton Trans; 1267-1272.
29. Gava B, Zorzet S, Spessotto P, Cocchietto M, Sava G (2006) Inhibition of B16 melanoma metastases with the ruthenium complex imidazolium trans-imidazoledimethylsulfoxide-tetrachlororuthenate and down-regulation of tumor cell invasion. J Pharmacol Exp Ther 317:284-291
30. Zorzet S, Bergamo A, Cocchietto M, Sorc A, Gava B, Alessio E, Iengo E, Sava G (2000) Lack of In vitro cytotoxicity, associated to increased G(2)-M cell fraction and inhibition of matrigel invasion, may predict In vivo-selective antimetastasis activity of ruthenium complexes. J Pharmacol Exp Ther 295:927-933
31. Debidda M, Sanna B, Cossu A, Posadino AM, Tadolini B, Ventura C, Pintus G (2003) NAMI-A inhibits the PMA-induced ODC gene expression in ECV304 cells: involvement of PKC/Raf/Mek/ERK signalling pathway. Int J Oncol 23:477-482
32. Sava G, Zorzet S, Turrin C, Vita F, Soranzo M, Zabucchi G, Cocchietto M, Bergamo A, DiGiovine S, Pezzoni G, Sartor L, Garbisa S (2003) Dual Action of NAMI-A in inhibition of solid tumor metastasis: selective targeting of metastatic cells and binding to collagen. Clin Cancer Res 9:1898-1905
33. Casarsa C, Mischis MT, Sava G (2004) TGFbeta1 regulation and collagen-release-independent connective tissue re-modelling by the ruthenium complex NAMI-A in solid tumours. J Inorg Biochem 98:1648-1654
34. Vacca A, Bruno M, Boccarelli A, Coluccia M, Ribatti D, Bergamo A, Garbisa S, Sartor L, Sava G (2002) Inhibition of endothelial cell functions and of angiogenesis by the metastasis inhibitor NAMI-A. Br J Cancer 86:993-998
35. Morbidelli L, Donnini S, Filippi S, Messori L, Piccioli F, Orioli P, Sava G, Ziche M (2003) Antiangiogenic properties of selected ruthenium(III) complexes that are nitric oxide scavengers. Br J Cancer 88:1484-1491
36. Bergamo A, Gagliardi R, Scarcia V, Furlani A, Alessio E, Mestroni G, Sava G (1999) In vitro cell cycle arrest, in vivo action on solid metastasizing tumors, and host toxicity of the antimetastatic drug NAMI-A and cisplatin. J Pharmacol Exp Ther 289:559-564
37. Bergamo A, Zorzet S, Gava B, Sorc A, Alessio E, Iengo E, Sava G (2000) Effects of NAMI-A and some related ruthenium complexes on cell viability after short exposure of tumor cells. Anticancer Drugs 11:665-672
38. Pintus G, Tadolini B, Posadino AM, Sanna B, Debidda M, Bennardini F, Sava G, Ventura C (2002) Inhibition of the MEK/ERK signaling pathway by the novel antimetastatic agent NAMI-A down regulates c-myc gene expression and endothelial cell proliferation. Eur J Biochem 269:5861-5870
39. Sanna B, Debidda M, Pintus G, Tadolini B, Posadino AM, Bennardini F, Sava G, Ventura C (2002) The anti-metastatic agent imidazolium trans-imidazoledimethylsulfoxide-tetrachlororuthenate induces endothelial cell apoptosis by inhibiting the mitogen-activated protein kinase/extracellular signal-regulated kinase signaling pathway. Arch Biochem Biophys 403:209-218
40. Pluim D, van Waardenburg RC, Beijnen JH, Schellens JH (2004) Cytotoxicity of the organic ruthenium anticancer drug Nami-A is correlated with DNA binding in four different human tumor cell lines. Cancer Chemother Pharmacol 54:71-78
41. Barca A, Pani B, Tamaro M, Russo E (1999) Molecular interactions of ruthenium complexes in isolated mammalian nuclei and cytotoxicity on V79 cells in culture. Mutat Res 423:171-181
42. Brabec V, Novakova O (2006) DNA binding mode of ruthenium complexes and relationship to tumor cell toxicity. Drug Resist Updat 9:111-122
43. Sava G, Pacor S, Mestroni G, Alessio E (1992) Effects of the Ru(III) complexes [mer-RuCl3(DMSO)2Im]degrees and Na[trans-RuCl4(DMSO)Im] on solid mouse tumors. Anticancer Drugs 3:25-31
44. Sava G, Capozzi I, Clerici K, Gagliardi G, Alessio E, Mestroni G (1998) Pharmacological control of lung metastases of solid tumours by a novel ruthenium complex. Clin Exp Metastasis 16:371-379
45. Sava G, Clerici K, Capozzi I, Cocchietto M, Gagliardi R, Alessio E, Mestroni G, Perbellini A (1999) Reduction of lung metastasis by ImH[trans-RuCl4(DMSO)Im]: mechanism of the selective action investigated on mouse tumors. Anticancer Drugs 10:129-138
46. Sava G, Gagliardi R, Bergamo A, Alessio E, Mestroni G (1999) Treatment of metastases of solid mouse tumours by NAMI-A: comparison with cisplatin, cyclophosphamide and dacarbazine. Anticancer Res 19:969-972
47. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European organization for research and treatment of cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205-216
48. Storer BE (1989) Design and analysis of phase I clinical trials. Biometrics 45:925-937
49. Cancer therapy evaluation program nci common terminology criteria version 3.0 (NCI-CTCv.3.0) March 31, 2003 Publish Date 09 August 2006 http://ctep.cancer.gov/protocolDevelopment/electronic-applications/docs/ctcaev3.pdf. 9-8-2006.Ref Type: internet communication
50. Crul M, van den Bongard HJ, Tibben MM, van Tellingen O, Sava G, Schellens JH, Beijnen JH (2001) Validated method for the determination of the novel organo-ruthenium anticancer drug NAMI-A in human biological fluids by Zeeman atomic absorption spectrometry. Fresenius J Anal Chem 369:442-445
51. Vainchtein LD, Rosing H, Thijssen B, Schellens JH, Beijnen JH (2007) Validated assay for the simultaneous determination of the anti-cancer agent gemcitabine and its metabolite 2',2'-difluorodeoxyuridine in human plasma by high-performance liquid chromatography with tandem mass spectrometry. Rapid Commun Mass Spectrom 21:2312-2322
52. Veltkamp SA, Hillebrand MJ, Rosing H, Jansen RS, Wickremsinhe ER, Perkins EJ, Schellens JH, Beijnen JH (2006) Quantitative analysis of gemcitabine triphosphate in human peripheral blood mononuclear cells using weak anion-exchange liquid chromatography coupled with tandem mass spectrometry. J Mass Spectrom 41:1633-1642
53. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van GM, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European organization for research and treatment of cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205-216
54. Simon R (1989) Optimal two-stage designs for phase II clinical trials. Control Clin Trials 10:1-10
55. Dickson, N. R., Jones, S. F., Burris, R. K., and et.al (2011) A phase I dose-escalation study of NKP-1339 in patients with advanced solid tumors refractory to treatment. J Clin Oncol (29 suppl; abstr 2607). Ref Type: Abstract
56. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van GM, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European organization for research and treatment of cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205-216
57. Cocchietto M, Sava G (2000) Blood concentration and toxicity of the antimetastasis agent NAMI-A following repeated intravenous treatment in mice. Pharmacol Toxicol 87:193-197
58. Sava G, Pacor S, Bergamo A, Cocchietto M, Mestroni G, Alessio E (1995) Effects of ruthenium complexes on experimental tumors: irrelevance of cytotoxicity for metastasis inhibition. Chem Biol Interact 95:109-126
59. Sava G, Cocchietto M (2000) Blood levels of ruthenium following repeated treatments with the antimetastatic compound NAMI-A in healthy beagle dogs. In Vivo 14:741-744
60. Bouma M, Nuijen B, Jansen MT, Sava G, Bult A, Beijnen JH (2002) Photostability profiles of the experimental antimetastatic ruthenium complex NAMI-A. J Pharm Biomed Anal 30:1287-1296
61. Bouma M, Nuijen B, Jansen MT, Sava G, Flaibani A, Bult A, Beijnen JH (2002) A kinetic study of the chemical stability of the antimetastatic ruthenium complex NAMI-A. Int J Pharm 248:239-246
62. Bouma M, Nuijen B, Sava G, Perbellini A, Flaibani A, van Steenbergen MJ, Talsma H, den Bosch JJ K-v, Bult A, Beijnen JH (2002) Pharmaceutical development of a parenteral lyophilized formulation of the antimetastatic ruthenium complex NAMI-A. Int J Pharm 248:247-259
63. Bouma M, Nuijen B, Jansen MT, Sava G, Picotti F, Flaibani A, Bult A, Beijnen JH (2003) Development of a LC method for pharmaceutical quality control of the antimetastatic ruthenium complex NAMI-A. J Pharm Biomed Anal 31:215-228
64. Sava G, Bergamo A, Zorzet S, Gava B, Casarsa C, Cocchietto M, Furlani A, Scarcia V, Serli B, Iengo E, Alessio E, Mestroni G (2002) Influence of chemical stability on the activity of the antimetastasis ruthenium compound NAMI-A. Eur J Cancer 38:427-435
65. Magnarin M, Bergamo A, Carotenuto ME, Zorzet S, Sava G (2000) Increase of tumour infiltrating lymphocytes in mice treated with antimetastatic doses of NAMI-A. Anticancer Res 20:2939-2944
66. Pacor S, Zorzet S, Cocchietto M, Bacac M, Vadori M, Turrin C, Gava B, Castellarin A, Sava G (2004) Intratumoral NAMI-A treatment triggers metastasis reduction, which correlates to CD44 regulation and tumor infiltrating lymphocyte recruitment. J Pharmacol Exp Ther 310:737-744
67. Vadori M, Pacor S, Vita F, Zorzet S, Cocchietto M, Sava G (2012) Features and full reversibility of the renal toxicity of the ruthenium-based drug NAMI-A in mice. J Inorg Biochem 118C:21-27