Nonclinical pharmacokinetics and activity of etirinotecan pegol (NKTR-102), a long-acting topoisomerase 1 inhibitor, in multiple cancer models

Cancer Chemotherapy and Pharmacology

Volumn 74, Issue 6, 2014, Pages 1125-1137

  Hoch, Ute ^a   Staschen, Carl Michael ^b   Johnson, Randall K ^c   Eldon, Michael A ^a  

^a NEKTAR THERAPEUTICS   (United States)

^b CENTER FOR DRUG EVALUATION AND RESEARCH   (United States)

^c Independent Consultant   (United States)

Author keywords

Anticancer activity; Etirinotecan pegol; Pharmacokinetics; SN38; Topoisomerase 1 inhibition

Indexed keywords

ETIRINOTECAN PEGOL; FIRTECAN; IRINOTECAN; ANTINEOPLASTIC AGENT; CAMPTOTHECIN; DNA TOPOISOMERASE INHIBITOR; FUSED HETEROCYCLIC RINGS; MACROGOL DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; BEAGLE; BLOOD SAMPLING; BREAST CANCER; CANCER INHIBITION; CANCER MODEL; COLORECTAL CANCER; CONTROLLED STUDY; DRUG ELIMINATION; DRUG METABOLISM; DRUG TOLERABILITY; DRUG TUMOR LEVEL; FEMALE; HUMAN; HUMAN CELL; LUNG CANCER; MALE; MOUSE; MOUSE MODEL; NONHUMAN; OUTCOME ASSESSMENT; OVARY CANCER; PHARMACOKINETICS; PLASMA CONCENTRATION-TIME CURVE; PLASMA HALF LIFE; RAT; SPECIES; STOMACH CANCER; ANALOGS AND DERIVATIVES; ANIMAL; COMPARATIVE STUDY; DOG; DRUG SCREENING; NEOPLASMS, EXPERIMENTAL; NUDE MOUSE; PATHOLOGY; SCID MOUSE; SPECIES DIFFERENCE; SPRAGUE DAWLEY RAT; TREATMENT OUTCOME;

ANIMALS; ANTINEOPLASTIC AGENTS; CAMPTOTHECIN; DOGS; FEMALE; HETEROCYCLIC COMPOUNDS WITH 4 OR MORE RINGS; HUMANS; MALE; MICE; MICE, NUDE; MICE, SCID; NEOPLASMS, EXPERIMENTAL; POLYETHYLENE GLYCOLS; RATS; RATS, SPRAGUE-DAWLEY; SPECIES SPECIFICITY; TOPOISOMERASE I INHIBITORS; TREATMENT OUTCOME; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84912033623     PISSN: 03445704     EISSN: 14320843     Source Type: Journal    
DOI: 10.1007/s00280-014-2577-7     Document Type: Article

References (48)

1. Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R (2007) Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol 2(12):751-760
2. ABI 007 (2004) Drugs R D 5:155-159
3. Gilead Sciences; Foster City (CA). Prescribing Information DaunoXome (1998)
4. Sigma-Tau Pharmaceuticals, Inc; Gaithersburg (MD). Prescribing information DepoCyt (1999)
5. Abraxis Biosciences; Bridgewater (NJ). Prescribing information Abraxane (2005)
6. Krown SE, Northfelt DW, Osoba D, Stewart JS (2004) Use of liposomal anthracyclines in Kaposi's sarcoma. Semin Oncol 31(6 Suppl 13):36-52
7. Markman M, Gordon AN, McGuire WP, Muggia FM (2004) Liposomal anthracycline treatment for ovarian cancer. Semin Oncol 31(6 Suppl 13):91-105
8. Pasut G, Veronese FM (2009) PEG conjugates in clinical development or use as anticancer agents: an overview. Adv Drug Deliv Rev 61(13):1177-1188
9. Zamboni WC (2005) Liposomal, nanoparticle, and conjugated formulations of anticancer agents. Clin Cancer Res 11(23):8230-8234
10. Chabot GG, Abigerges D, Catimel G, Culine S, de Forni M, Extra JM, Mahjoubi M, Herait P, Armand JP, Bugat R et al (1995) Population pharmacokinetics and pharmacodynamics of irinotecan (CPT-11) and active metabolite SN-38 during phase I trials. Ann Oncol 6(2):141-151
11. Pommier Y (2006) Topoisomerase I inhibitors: camptothecins and beyond. Nat Rev Cancer 6(10):789-802
12. Saltz LB, Cox JV, Blanke C, Rosen LS, Fehrenbacher L, Moore MJ, Maroun JA, Ackland SP, Locker PK, Pirotta N, Elfring GL, Miller LL, Irinotecan Study Group (2000) Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. N Engl J Med 343(13):905-914
13. Douillard JY, Cunningham D, Roth AD, Navarro M, James RD, Karasek P, Jandik P, Iveson T, Carmichael J, Alakl M, Gruia G, Awad L, Rougier P (2000) Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet 355(9209):1041-1047
14. Freyer G, Rougier P, Bugat R, Droz JP, Marty M, Bleiberg H, Mignard D, Awad L, Herait P, Culine S, Trillet-Lenoir V, CPT-11 F205, F220, F221 and V222 study groups (2000) Prognostic factors for tumour response, progression-free survival and toxicity in metastatic colorectal cancer patients given irinotecan (CPT-11) as second-line chemotherapy after 5FU failure. Br J Cancer 83(4):431-437
15. Hanna N, Bunn PA Jr, Langer C, Einhorn L, Guthrie T Jr, Beck T, Ansari R, Ellis P, Byrne M, Morrison M, Hariharan S, Wang B, Sandler A (2006) Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol 24(13):2038-2043
16. Ohe Y, Ohashi Y, Kubota K, Tamura T, Nakagawa K, Negoro S, Nishiwaki Y, Saijo N, Ariyoshi Y, Fukuoka M (2007) Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: four-Arm Cooperative Study in Japan. Ann Oncol 18(2):317-323
17. Shah MA, Ramanathan RK, Ilson DH, Levnor A, D'Adamo D, O'Reilly E, Tse A, Trocola R, Schwartz L, Capanu M, Schwartz GK, Kelsen DP (2006) Multicenter phase II study of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol 24(33):5201-5206
18. Park SR, Chun JH, Yu MS, Lee JH, Ryu KW, Choi IJ, Kim CG, Lee JS, Kim YW, Bae JM, Kim HK (2006) Phase II study of docetaxel and irinotecan combination chemotherapy in metastatic gastric carcinoma. Br J Cancer 94(10):1402-1406
19. Raymond E, Fabbro M, Boige V, Rixe O, Frenay M, Vassal G, Faivre S, Sicard E, Germa C, Rodier JM, Vernillet L, Armand JP (2003) Multicentre phase II study and pharmacokinetic analysis of irinotecan in chemotherapy-naive patients with glioblastoma. Ann Oncol 14(4):603-614
20. Selvaggi L, Loizzi V, Di Gilio AR, Nardelli C, Cantatore C, Cormio G (2006) Neoadjuvant chemotherapy in cervical cancer: a 67 patients experience. Int J Gynecol Cancer 16(2):631-637
21. Perez EA, Hillman DW, Mailliard JA, Ingle JN, Ryan JM, Fitch TR, Rowland KM, Kardinal CG, Krook JE, Kugler JW, Dakhil SR (2004) Randomized phase II study of two irinotecan schedules for patients with metastatic breast cancer refractory to an anthracycline, a taxane, or both. J Clin Oncol 22(14):2849-2855
22. Ribrag V, Koscielny S, Vantelon JM, Ferme C, Rideller K, Carde P, Bourhis JH, Munck JN (2003) Phase II trial of irinotecan (CPT-11) in relapsed or refractory non-Hodgkin's lymphomas. Leuk Lymphoma 44(9):1529-1533
23. Hertzberg RP, Caranfa MJ, Hecht SM (1989) On the mechanism of topoisomerase I inhibition by camptothecin: evidence for binding to an enzyme-DNA complex. Biochemistry 28(11):4629-4638
24. Kawato Y, Aonuma M, Hirota Y, Kuga H, Sato K (1991) Intracellular roles of SN-38, a metabolite of the camptothecin derivative CPT-11, in the antitumor effect of CPT-11. Cancer Res 51(16):4187-4191
25. Pitot HC, Goldberg RM, Reid JM, Sloan JA, Skaff PA, Erlichman C, Rubin J, Burch PA, Adjei AA, Alberts SA, Schaaf LJ, Elfring G, Miller LL (2000) Phase I dose-finding and pharmacokinetic trial of irinotecan hydrochloride (CPT-11) using a once-every-three-week dosing schedule for patients with advanced solid tumor malignancy. Clin Cancer Res 6(6):2236-2244
26. Kehrer DF, Yamamoto W, Verweij J, de Jonge MJ, de Bruijn P, Sparreboom A (2000) Factors involved in prolongation of the terminal disposition phase of SN-38: clinical and experimental studies. Clin Cancer Res 6(9):3451-3458
27. Chabot GG (1997) Clinical pharmacokinetics of irinotecan. Clin Pharmacokinet 33(4):245-259
28. Masi G, Falcone A, Di Paolo A, Allegrini G, Danesi R, Barbara C, Cupini S, Del Tacca M (2004) A phase I and pharmacokinetic study of irinotecan given as a 7-day continuous infusion in metastatic colorectal cancer patients pretreated with 5-fluorouracil or raltitrexed. Clin Cancer Res 10(5):1657-1663
29. Takimoto CH, Morrison G, Harold N, Quinn M, Monahan BP, Band RA, Cottrell J, Guemei A, Llorens V, Hehman H, Ismail AS, Flemming D, Gosky DM, Hirota H, Berger SJ, Berger NA, Chen AP, Shapiro JD, Arbuck SG, Wright J, Hamilton JM, Allegra CJ, Grem JL (2000) Phase I and pharmacologic study of irinotecan administered as a 96-hour infusion weekly to adult cancer patients. J Clin Oncol 18(3):659-667
30. Herben VM, Schellens JH, Swart M, Gruia G, Vernillet L, Beijnen JH, ten Bokkel Huinink WW (1999) Phase I and pharmacokinetic study of irinotecan administered as a low-dose, continuous intravenous infusion over 14 days in patients with malignant solid tumors. J Clin Oncol 17(6):1897-1905
31. Gabrielsson J, Weiner D (2000) Pharmacokinetic and pharmacodynamic data analysis: concepts and applications. pharmacokinetic and pharmacodynamic data analysis: concepts and applications, 3rd edn. Swedish Pharmaceutical Press, Stockholm
32. Simeoni M, Magni P, Cammia C, De Nicolao G, Croci V, Pesenti E, Germani M, Poggesi I, Rocchetti M (2004) Predictive pharmacokinetic-pharmacodynamic modeling of tumor growth kinetics in xenograft models after administration of anticancer agents. Cancer Res 64(3):1094-1101
33. Reagan-Shaw S, Nihal M, Ahmad N (2008) Dose translation from animal to human studies revisited. FASEB J 22(3):659-661
34. Maeda H, Wu J, Sawa T, Matsumura Y, Hori K (2000) Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 65(1-2):271-284
35. Fang J, Sawa T, Maeda H (2003) Factors and mechanism of "EPR" effect and the enhanced antitumor effects of macromolecular drugs including SMANCS. Adv Exp Med Biol 519:29-49
36. Minko T, Dharap SS, Pakunlu RI, Wang Y (2004) Molecular targeting of drug delivery systems to cancer. Curr Drug Targets 5(4):389-406
37. Lammers T, Kiessling F, Hennink WE, Storm G (2012) Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress. J Control Release 161(2):175-187
38. Jameson GS, Hamm JT, Weiss GJ, Alemany C, Anthony S, Basche M, Ramanathan RK, Borad MJ, Tibes R, Cohn A, Hinshaw I, Jotte R, Rosen LS, Hoch U, Eldon MA, Medve R, Schroeder K, White E, Von Hoff DD (2013) A multicenter, phase I, dose-escalation study to assess the safety, tolerability, and pharmacokinetics of etirinotecan pegol in patients with refractory solid tumors. Clin Cancer Res 19(1):268-278
39. Kim J, Bayever E, Laivins P, Niyikiza C, Nielsen U, Fitzgerald J, Kalra A, Chalishazar M, Klinz S, Paz N, Hendriks B, Drummond D, Kirpotin D, Moyo V (2012) Sustained intratumoral activation of MM-398 results in superior activity over irinotecan demonstrated by using a systems pharmacology approach. Cancer Res 72(13 Suppl 2):A6
40. Sapra P, Zhao H, Mehlig M, Malaby J, Kraft P, Longley C, Greenberger LM, Horak ID (2008) Novel delivery of SN38 markedly inhibits tumor growth in xenografts, including a camptothecin-11-refractory model. Clin Cancer Res 14(6):1888-1896
41. Matsumura Y (2011) Preclinical and clinical studies of NK012, an SN-38-incorporating polymeric micelles, which is designed based on EPR effect. Adv Drug Deliv Rev 63(3):184-192
42. Matsuzaki T, Takagi A, Furuta T, Ueno S, Kurita A, Nohara G, Kodaira H, Sawada S, Hashimoto S (2012) Antitumor activity of IHL-305, a novel pegylated liposome containing irinotecan, in human xenograft models. Oncol Rep 27(1):189-197
43. Chen L, Chang T, Cheng C, Yang C, Shiah H, Chang J, Yeh G (2008) Phase I study of liposome encapsulated irinotecan (PEP02) in advanced solid tumor patients. J Clin Oncol (Meeting Abstracts) 26(suppl 15):2565
44. Kurzrock R, Goel S, Wheler J, Hong D, Fu S, Rezai K, Morgan-Linnell SK, Urien S, Mani S, Chaudhary I, Ghalib MH, Buchbinder A, Lokiec F, Mulcahy M (2012) Safety, pharmacokinetics, and activity of EZN-2208, a novel conjugate of polyethylene glycol and SN38, in patients with advanced malignancies. Cancer 118(24):6144-6151
45. Hamaguchi T, Doi T, Eguchi-Nakajima T, Kato K, Yamada Y, Shimada Y, Fuse N, Ohtsu A, Matsumoto S, Takanashi M, Matsumura Y (2010) Phase I study of NK012, a novel SN-38-incorporating micellar nanoparticle, in adult patients with solid tumors. Clin Cancer Res 16(20):5058-5066
46. Infante JR, Keedy VL, Jones SF, Zamboni WC, Chan E, Bendell JC, Lee W, Wu H, Ikeda S, Kodaira H, Rothenberg ML, Burris HA 3rd (2012) Phase I and pharmacokinetic study of IHL-305 (PEGylated liposomal irinotecan) in patients with advanced solid tumors. Cancer Chemother Pharmacol 70(5):699-705
47. Vergote IB, Garcia A, Micha J, Pippitt C, Bendell J, Spitz D, Reed N, Dark G, Fracasso PM, Ibrahim EN, Armenio VA, Duska L, Poole C, Gennigens C, Dirix LY, Leung AC, Zhao C, Soufi-Mahjoubi R, Rustin G (2013) Randomized multicenter phase II trial comparing two schedules of etirinotecan pegol (NKTR-102) in women with recurrent platinum-resistant/refractory epithelial ovarian cancer. J Clin Oncol 31(32):4060-4066
48. Awada A, Garcia AA, Chan S, Jerusalem GH, Coleman RE, Huizing MT, Mehdi A, O'Reilly SM, Hamm JT, Barrett-Lee PJ, Cocquyt V, Sideras K, Young DE, Zhao C, Chia YL, Hoch U, Hannah AL, Perez EA (2013) Two schedules of etirinotecan pegol (NKTR-102) in patients with previously treated metastatic breast cancer: a randomised phase 2 study. Lancet Oncol 14(12):1216-1225