Mipsagargin, a novel thapsigargin-based PSMA-Activated prodrug: Results of a first-in-man phase i clinical trial in patients with refractory, advanced or metastatic solid tumours

British Journal of Cancer

Volumn 114, Issue 9, 2016, Pages 986-994

  Mahalingam, D ^a   Wilding, G ^b   Denmeade, S ^c   Sarantopoulas, J ^a   Cosgrove, D ^d   Cetnar, J ^b   Azad, N ^d   Bruce, J ^b   Kurman, M ^e   Allgood, V E ^e   Carducci, M ^d  

^a UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO   (United States)

^b UNIVERSITY OF WISCONSIN   (United States)

^c JOHNS HOPKINS UNIVERSITY   (United States)

^d JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e Medical Monitor   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIEMETIC AGENT; ANTIHISTAMINIC AGENT; ANTIPYRETIC AGENT; ASPARTATE AMINOTRANSFERASE; CREATININE; GAMMA GLUTAMYLTRANSFERASE; HISTAMINE H2 RECEPTOR ANTAGONIST; MIPSAGARGIN; STEROID; ENZYME INHIBITOR; PRODRUG; THAPSIGARGIN;

ABDOMINAL PAIN; ACUTE KIDNEY FAILURE; ADULT; ADVANCED CANCER; AGED; ANEMIA; ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTHRALGIA; ARTICLE; ASCITES; BLEEDING; CANCER CONTROL; CHILL; CLINICAL ARTICLE; CONSTIPATION; CONTROLLED STUDY; COUGHING; DECREASED APPETITE; DIARRHEA; DISEASE COURSE; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG HALF LIFE; DRUG METABOLISM; DRUG SAFETY; DRUG STRUCTURE; DYSPEPSIA; DYSPNEA; FATIGUE; FEBRILE NEUTROPENIA; FEMALE; FEVER; HAPLORHINI; HUMAN; HYDRATION; HYPERGLYCEMIA; HYPERKALEMIA; HYPOTENSION; INFUSION RELATED REACTION; KIDNEY INJURY; MALE; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUTROPENIA; NONHUMAN; PHASE 1 CLINICAL TRIAL; PREMEDICATION; PRIORITY JOURNAL; PROTEINURIA; PRURITUS; RASH; RAT; RECOMMENDED DRUG DOSE; SIDE EFFECT; SOLID TUMOR; THROMBOCYTOPENIA; TREATMENT OUTCOME; TREATMENT RESPONSE; URINARY TRACT INFECTION; VOMITING; CLINICAL TRIAL; MIDDLE AGED; NEOPLASMS; VERY ELDERLY;

AGED; AGED, 80 AND OVER; ENZYME INHIBITORS; HUMANS; MALE; MIDDLE AGED; NEOPLASMS; PRODRUGS; THAPSIGARGIN;

EID: 84964674918     PISSN: 00070920     EISSN: 15321827     Source Type: Journal    
DOI: 10.1038/bjc.2016.72     Document Type: Article

References (44)

1. Breckenridge DG, Germain M, Mathai JP, Nguyen M, Shore GC (2003) Regulation of apoptosis by endoplasmic reticulum pathways. Oncogene 22: 8608-8618.
2. Chang SS, OKeefe DS, Bacich DJ, Reuter VE, Heston WD, Gaudin PB (1999a) Prostate specific membrane antigen is produced in tumor-Associated neovasculature. Clin Cancer Res 5: 2674-2681.
3. Chang SS, Reuter VE, Heston WD, Bander NH, Grauer LS, Gaudin PB (1999b) Five different anti-prostate-specific membrane antigen (PSMA) antibodies confirm PSMA expression in tumor-Associated neovasculature. Cancer Res 59: 3192-3198.
4. Coors EA, Seybold H, Merk HF, Mahler V (2005) Polysorbate 80 in medical products and nonimmunologic anaphylactoid reactions. Ann Allergy Asthma Immunol 95: 593-599.
5. Deniaud A, Sharaf el dein O, Malillier E, Poncet D, Kroemer G, Lemaire C, Brenner C (2008) Endoplasmic reticulum stress induces calciumdependent permeability transition, mitochondrial outer membrane permeabilization and apoptosis. Oncogene 27: 285-299.
6. Denmeade SR, Isaacs JT (1998) Enzymatic activation of prodrugs by prostatespecific antigen: Targeted therapy for metastatic prostate cancer. Cancer J Sci Am 4(Suppl 1): S15-S21.
7. Denmeade SR, Isaacs JT (2005) The SERCA pump as a therapeutic target: Making a smart bomb for prostate cancer. Cancer Biol Ther 4: 14-22.
8. Denmeade SR, Jakobsen CM, Janssen S, Khan SR, Garrett ES, Lilja H, Christensen SB, Isaacs JT (2003) Prostate-specific antigen-Activated thapsigargin prodrug as targeted therapy for prostate cancer. J Natl Cancer Inst 95: 990-1000.
9. Denmeade SR, Lin XS, Tombal B, Isaacs JT (1999) Inhibition of caspase activity does not prevent the signaling phase of apoptosis in prostate cancer cells. Prostate 39: 269-279.
10. Denmeade SR, Mhaka AM, Rosen DM, Brennen WN, Dalrymple S, Dach I, Olesen C, Gurel B, DeMarzo AM, Wilding G, Carducci MA, Dionne CA, Moller JV, Nissen P, Christensen SB, Isaacs JT (2012) Engineering a prostate-specific membrane antigen-Activated tumor endothelial cell prodrug for cancer therapy. Sci Trans Med 4: 1-12.
11. Doronina SO, Toki BE, Torgov MY, Mendelsohn BA, Cerveny CG, Chace DF, DeBlanc RL, Gearing RP, Bovee TD, Siegall CB, Francisco JA, Wahl AF, Meyer DL, Senter PD (2003) Development of potent monoclonal antibody auristatin conjugates for cancer therapy. Nat Biotechnol 21: 778-784.
12. Finn RS, Kang YK, Mulcahy M, Polite BN, Lim HY, Walters I, Baudelet C, Manekas D, Park JW (2012) Phase II open-label study of brivanib as second-line therapy in patients with advanced hepatocellular carcinoma. Clin Cancer Res 18: 2090-2098.
13. Furuya Y, Krajewski S, Epstein JI, Reed JC, Isaacs JT (1996) Expression of bcl-2 and the progression of human and rodent prostatic cancers. Clin Cancer Res 2: 389-398.
14. Furuya Y, Lundmo P, Short AD, Gill DL, Isaacs JT (1994) The role of calcium, pH, and cell proliferation in the programmed (apoptotic) death of androgen-independent prostatic cancer cells induced by thapsigargin. Cancer Res 54: 6167-6175.
15. Galsky MD, Eisenberger M, Moore-Cooper S, Kelly WK, Slovin SF, DeLaCruz A, Lee Y, Webb IJ, Scher HI (2008) Phase I trial of the prostate-specific membrane antigen-directed immunoconjugate MLN2704 in patients with progressive metastatic castration-resistant prostate cancer. J Clin Oncol 26: 2147-2154.
16. Haffner MC, Kronberger IE, Ross JS, Sheehan CE, Zitt M, Mühlmann G, Ofner D, Zelger B, Ensinger C, Yang XJ, Geley S, Margreiter R, Bander NH (2009) Prostate-specific membrane antigen expression in the neovasculature of gastric and colorectal cancers. Hum Pathol 40: 1754-1761.
17. Huber M, Hughes MR, Krystal G (2000) Thapsigargin-induced degranulation of mast cells is dependent on transient activation of phosphatidylinositiol-3 kinase. J Immunol 165: 124-133.
18. Jakobsen CM, Denmeade SR, Isaacs JT, Gady A, Olsen CE, Christensen SB (2001) Design, synthesis, and pharmacological evaluation of thapsigargin analogues for targeting apoptosis to prostatic cancer cells. J Med Chem 44: 4696-4703.
19. Lin XS, Denmeade SR, Cisek L, Isaacs JT (1997) Mechanism and role of growth arrest in programmed (apoptotic) death of prostatic cancer cells induced by thapsigargin. Prostate 33: 201-207.
20. Liu H, Moy P, Kim S, Xia Y, Rajasekaran A, Navarro V, Knudsen B, Bander NH (1997) Monoclonal antibodies to the extracellular domain of prostate-specific membrane antigen also react with tumor vascular endothelium. Cancer Res 57: 3629-3634.
21. Llovet JM, Decaens T, Raoul JL, Boucher E, Kudo M, Chang C, Kang YK, Assenat E, Lim HY, Boige V, Mathurin P, Fartoux L, Lin DY, Bruix J, Poon RT, Sherman M, Blanc JF, Finn R, Tak WY, Chao Y, Ezzeddine R, Liu D, Walters I, Park JW (2012) Brivanib versus placebo in patients with advanced hepatocellular carcinoma (HCC) who failed or were intolerant to sorafenib: results from the phase 3 BRISK-PS Study. ILC 2012. Abstract 1398.
22. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, Cosme de Oliveira A, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359: 378-390.
23. Ma D, Hopf CE, Malewicz AD, Donovan GP, Senter PD, Goeckeler WF, Maddon PJ, Olson WC (2006) Potent antitumor activity of an auristatin-conjugated, fully human monoclonal antibody to prostate-specific membrane antigen. Clin Cancer Res 12: 2591-2596.
24. Petrylak DP, Kantoff PW, Mega AE, Vogelzang NJ, Stephenson J, Fleming MT, Stambler N, Petrini M, Blattman S, Israel RJ (2013) Prostate-specific membrane antigen antibody drug conjugate (PSMA ADC): A phase I trial in metastatic castration-resistant prostate cancer (mCRPC) previously treated with a taxane. J Clin Oncol 31(Suppl 6): Abstract 119.
25. Petrylak DP, Smith DC, Appleman LJ, Fleming MT, Hussain A, Dreicer R, Sartor AO, Shore N, Vogelzang NJ, Youssoufian H, DiPippo VA, Stambler N, Huang K, Israel RJ (2014) A phase II trial of prostate-specific membrane antigen antibody drug conjugate (PSMA ADC) in taxanerefractory metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol 32(Suppl): Abstract 5023.
26. Putney Jr JW, Bird GS (1993) The signal for capacitative calcium entry. Cell 75: 199-201.
27. Randriamampita C, Tsien RY (1993) Emptying of intracellular Ca2+ stores releases a novel small messenger that stimulates Ca2+ influx. Nature 364: 809-814.
28. Rao RV, Castro-Obregon S, Frankowski H, Schuler M, Stoka V, del Rio G, Bredesen DE, Ellerby HM (2002) Coupling endoplasmic reticulum stress to the cell death program. An Apaf-1-independent intrinsic pathway. J Biol Chem 277: 21836-21842.
29. Rasmussen U, Christensen SB, Sandberg F (1978) Thapsigargine and thapsigargicine, two new histamine liberators from Thapsia garganica L. Acta Pharm Suec 15: 133-140.
30. Samplaski MK, Heston W, Elson P, Magi-Galluzzi C, Hansel DE (2011) Folate hydrolase (prostate specific antigen) 1 expression in bladder cancer subtypes and associated tumor neovasculature. Mod Pathol 24: 1521-1529.
31. Silver DA, Pellicer I, Fair WR, Heston WDW, Cordon-Cardo C (1997) Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res 3: 81-85.
32. Singh P, Mhaka AM, Christensen SB, Gray JJ, Denmeade SR, Isaacs JT (2005) Applying linear interaction energy method for rational design of noncompetitive allosteric inhibitors of the sarco-And endoplasmic reticulum calcium-ATPase. J Med Chem 48: 3005-3014.
33. Søhoel H, Jensen AM, Møller JV, Nissen P, Denmeade SR, Isaacs JT, Olsen CE, Christensen SB (2006) Natural products as starting materials for development of second generation SERCA inhibitors targeted towards prostate cancer cells. Bioorg Med Chem 14: 2810-2815.
34. Tabas I, Ron D (2011) Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat Cell Biol 13: 184-190.
35. Tagawa ST, Milowsky MI, Morris M, Vallabhajosula S, Christos P, Akhtar NH, Osborne J, Goldsmith SJ, Larson S, Taskar NP, Scher HI, Bander NH, Nanus DM (2013) Phase II study of Lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for metastatic castration-resistant prostate cancer. Clin Cancer Res 19: 5182-5191.
36. Thastrup O, Cullen PJ, Drøbak BK, Hanley MR, Dawson AP (1990) Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2+-ATPase. Proc Natl Acad Sci USA 87: 2466-2470.
37. Tombal B, Denmeade SR, Gillis JM, Isaacs JT (2002) A supramicromolar elevation of intracellular free calcium ([Ca2+]i) is consistently required to induce the execution phase of apoptosis. Cell Death Differ 9: 561-573.
38. Tombal B, Denmeade SR, Isaacs JT (1999) Assessment and validation of a microinjection method for kinetic analysis of [Ca2+]i in individual cells undergoing apoptosis. Cell Calcium 25: 19-28.
39. Tombal B, Weeraratna AT, Denmeade SR, Isaacs JT (2000) Thapsigargin induces a calmodulin/calcineurin-dependent apoptotic cascade responsible for the death of prostatic cancer cells. Prostate 43: 303-317.
40. Toyoshima C, Nomura H, Sugita Y (2003) Crystal structures of Ca2+-ATPase in various physiological states. Ann NY Acad Sci 986: 1-8.
41. WinNonlin (2011) Phoenix Version 6.2.1. Pharsight Corporation Inc.: Mountain View, CA.
42. Winther AM, Liu H, Sonntag Y, Olesen C, Le Maire M, Soehoe Hl, Olsen CE, Christensen SB, Nissen P, Møller JV (2010) Critical roles of hydrophobicity and orientation of side chains for inactivation of sarcoplasmic reticulum Ca2+-ATPase with thapsigargin and thapsigargin analogs. J Biol Chem 285: 28883-28892.
43. Yang ZF, Poon RTP (2008) Vascular changes in hepatocellular carcinoma. Anat Rec 291: 721-734.
44. Yau T, Wong H, Chan P, Yao TJ, Pang R, Cheung TT, Fan ST, Poon RT (2012) Phase II study of bevacizumab and erlotonib in the treatment of advanced hepatocellular patients with sorafenib-refractory disease. Invest New Drugs 30: 2384-2390.