Exatecan Mesilate: Anticancer Agent DNA Topoisomerase I Inhibitor

Drugs of the Future

Volumn 29, Issue 1, 2004, Pages 9-22

  Chilman Blair, K ^a   Mealy, N E ^a   Castaner J ^a   Bayes M ^a  

^a PROUS SCIENCE   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; CYTOCHROME P450 1A2; CYTOCHROME P450 3A4; DNA TOPOISOMERASE INHIBITOR; EXATECAN; GEMCITABINE; IRINOTECAN; TOPOTECAN;

ADULT RESPIRATORY DISTRESS SYNDROME; ALOPECIA; ANEMIA; ANTINEOPLASTIC ACTIVITY; BILE DUCT CANCER; BONE MARROW TOXICITY; BREAST CANCER; CANCER INHIBITION; CLINICAL TRIAL; COLORECTAL CANCER; CONSTIPATION; DIARRHEA; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG METABOLISM; DRUG SAFETY; DRUG STRUCTURE; DRUG SYNTHESIS; ESOPHAGUS CANCER; FATIGUE; FEVER; GALLBLADDER CANCER; GASTROINTESTINAL SYMPTOM; HEADACHE; HUMAN; KIDNEY CANCER; LEUKOPENIA; LIVER CANCER; LUNG CANCER; MYALGIA; NAUSEA; NEUTROPENIA; OVARY CANCER; PANCREAS CANCER; PARESTHESIA; PERITONEUM CANCER; REVIEW; SEPSIS; STOMACH CANCER; STOMATITIS; THROMBOCYTOPENIA; VOMITING;

EID: 1342269596     PISSN: 03778282     EISSN: None     Source Type: Journal    
DOI: 10.1358/dof.2004.029.01.778296     Document Type: Review

References (58)

1. Terasawa, H., Sato, K., Mitsui, I. (Daiichi Pharmaceutical Co., Ltd.; Yakult Honsha Co., Ltd.). Antitumor agents. JP 1994087746.
2. Terasawa, H., Ejima, A., Ohsuki, S., Uoto, K. (Daiichi Pharmaceutical Co., Ltd.; Yakult Honsha Co., Ltd.). Hexa-cyclic cpd. JP 1993059061, EP 0495432, US 5834476, US 6407115.
3. Kamihara, S., Kanai, K., Noguchi, S., Terasawa, H., Kitaoka, H. (Daiichi Pharmaceutical Co., Ltd.; Yakult Honsha Co., Ltd.). Campthothecin deriv. with antitumour activity. CA 2173671, EP 0737686, JP 1996337584.
4. Garcia-Carbonero, R., Supko, J. Current perspectives on the clinical experience, pharmacology, and continued development of the camptothecins. Clin Cancer Res 2002, 8: 641-61.
5. Wall, M.E., Wani, M.C., Cook, C.E., Palmer, K.H., McPhail, H.T., Sim, G.A. Plant antitumor agents. I. The isolation and structure of camptothecin, a novel alkaloid leukemia and tumor inhibitor from Camptotheca acuminata. J Am Chem Soc 1966, 88: 3888-90.
6. Hsiang, Y.-H., Hertzberg, R., Hecht, S., Liu, L.F. Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. J Biol Chem 1985, 260: 14873-8.
7. Creaven, P.J., Allen, L.M. Renal clearance of camptothecin (NSC-100880): Effect of urine volume. Cancer Chemother Rep 1973, 57: 175-84.
8. Gottlieb, J.A., Guarino, A.M., Call, J.B., Oliverio, V.T., Block, J.B. Preliminary pharmacologic and clinical evaluation of camptothecin sodium (NSC-100880). Cancer Chemother Rep 1970, 54: 461-70.
9. van Hattum, A., Schlüper, H.M.M., Pinedo, H.M., Boven, E. Preclinical activity of DX-8951f (exatecan mesylate) and induction of breast cancer resistance protein (BCRP) as a mechanism of resistance. Proc Am Assoc Cancer Res 2001, 42: Abst 4372.
10. Ikeda, K., Terashima, M., Sasaki, N. et al. Preclinical evaluation of four kinds of camptothecin analogs against human malignancies. 7th Int Congr Anti-Cancer Treat (Feb 3-6, Paris) 1997, Abst P349.
11. Mitsui, I., Kumazawa, E., Hirota, K., Aonuma, M., Sugimori, M., Ohsuki, S., Uoto, K., Ejima, A., Terasawa, H., Sato, K. A new water-soluble camptothecin derivative, DX-8951f, exhibits potent antitumor activity against human tumors in vitro and in vivo. Jpn J Cancer Res 1995, 86: 776-82.
12. Kumazawa, E., Ochi, Y., Nakayama, Y., Iwahana, Y., Aonuma, M., Tanaka, N., Tohgo, A. Antitumor efficacy of DX-8951, a new camptothecin derivative, in various murine models. Proc Am Assoc Cancer Res 1995, 36: Abst 2627.
13. Vey, N., Jeha, S., Beran, M., Kantarjian, M., Sakamoto, N., DeJager, R., Giles, F.J. In vivo activity of different dose schedules of the topoisomerase inhbitor DX-8951f against human AML engrafted in SCID mice. Proc Am Soc Clin Oncol 1999, 18: Abst 149.
14. Vey, N., Giles, F., Kantarjian, H., Smith, T., Beran, M., Jeha, S. The topoisomerase I inhibitor DX-8951f is active in a severe combined immunodeficient mouse model of human acute myelogenous leukemia. Clin Cancer Res 2000, 6: 731-6.
15. Lawrence, R., Izbicka, E., De Jager, R., Tohgo, A., Clark, G., Weitman, S., Rowinsky, E.K., Von Hoff, D.D. Comparison of DX-8951f and topotecan effects on tumor colony formation from freshly explanted adult and pediatric human tumor cells. AntiCancer Drugs 1999, 10: 655-61.
16. DX-8951f Investigator's Brochure. Daiichi Pharmaceutical Corp.
17. Atsumi, R., Oguma, T., Yoshioka, N., Konno, T., Okazaki, O., Fujimaki, Y. Urinary metabolites of DX-8951, a novel camptothecin analog, in rats and humans. Arzneim-Forsch Drug Res 2001, 51: 253-7.
18. De Jager, R., Oguma, T., Kajimura, T. et al. Comparison of DX-8951f clinical and pre-clinical toxicokinetics (TK). Proc Am Soc Clin Oncol 1999, 18: Abst 686.
19. Sharma, S., Kemeny, N., Schwartz, G. et al. A phase I study of topoisomerase I inhibitor DX-8951f given as a continuous infusion over 24 hours every three weeks. Proc Am Soc Clin Oncol 1999, 18: Abst 683.
20. Rowinsky, E., Johnson, T., Geyer, C. et al. DX-8951f, a hexacyclic camptothecin analog, on a daily-times-five schedule: A phase I and pharmacokinetic study in patients with advanced solid malignancies. J Clin Oncol 2000, 18: 3151-63.
21. Royce, M., Hoff, P., Dumas, P., Lassere, Y., Lee, J., Coyle, J., Ducharme, M.P., De Jager, R., Pazdur, R. Phase I and pharmacokinetic study of exatecan mesylate (DX-8951f): A novel camptothecin analog. J Clin Oncol 2001, 19: 1493-500.
22. Royce, M., Hoff, P., Brito, R., Matei, C., Slaughter, M., Medgyesy, D., Lassere, Y., Lee, J., Coyle, J., De Jager, R.L., Pazdur, R. Phase I and trial of DX-8951f, a novel camptothecin analog, administered by 24-hour continuous infusion. Proc Am Soc Clin Oncol 1998, 17: Abst 757.
23. Hoff, P., Lassere, Y., Royce, M., Matei, C., Slaughter, M., Medgyesy, D., Lee, J., Coyle, J., De Jager, R.L., Pazdur, R. Phase I study of the new camptothecin analog DX-8951F administered by 24-hour continuous infusion. 10th NCI-EORTC Symp New Drugs Cancer Ther (June 16-19, Amsterdam) 1998, Abst 246.
24. Royce, M., Lassere, Y., Hoff, P., Brito, R., Ravandi, F., Coyle, J., De Jager, R., Pazdur, R. DX-8951f: Phase I and pharmacokinetic study of a novel camptothecin analog administered by 24-hour continuous infusion to patients with advanced solid tumors. Proc Am Soc Clin Oncol 1999, 18: Abst 682.
25. Sharma, S., Kemeny, N., Schwartz, G. et al. Phase I study of topoisomerase I inhibitor exatecan mesylate (DX-8951f) given as weekly 24-hour infusions three of every four weeks. Clin Cancer Res 2001, 7: 3963-70.
26. Thomas, C., Hammond, L., Geyer C.E. et al. A phase I and pharmacokinetic study of the hexacyclic topoisoerase I (Topo-I) inhibitor DX-8951f (exatecan) administered as a 5- to 21-day protracted continuous intravenous infusion (PCI). Proc Am Soc Clin Oncol 2001, 20: Abst 417.
27. Braybrooke, J., Boven, E., Bates, N., Ruijter, R., Dobbs, N., Cheverton, P., Pinedo, H.M., Talbot, D.C. Phase I and pharmacokinetic study of the topoisomerase I inhibitor, exatecan mesylate (DX-8915f), using a weekly 30-minute intravenous infusion, in patients with advanced solid malignancies. Ann Oncol 2003, 14: 913-21.
28. Bates, N., Boven, E., Dobbs, N., Varcoe, S., Ruijter, R., O'Grady, J., Pinedo, H.M., Talbot, D.C. Phase I and pharmacokinetic study of DX-8915f, a novel topoisomerase I inhibitor. Proc Am Soc Clin Oncol 1999, 18: Abst 684.
29. Minami, H., Fujii, H., Igarashi, T., Itoh, K., Tamanoi, K., Oguma, T., Sasaki, Y. Phase I and pharmacological study of a new camptothecin derivative, exatecan mesylate (DX-8951f), infused over 30 minutes every three weeks. Clin Cancer Res 2001, 7: 3056-64.
30. Boige, V., Raymond, E., Faivre, S., Gatineau, M., Meely, K., Mekhaldi, S., Pautier, P., Ducreux, M., Rixe, O., Armand, J.-P. Phase I and pharmacokinetic study of the camptothecin analog DX-8915f administered as a 30-minute infusion every 3 weeks in patients with advanced cancer. J Clin Oncol 2000, 18: 3986-92.
31. Raymond, E., Boige, V., Gatineau, M., Frazer, S., Laroche, C., Labbe, S., Paultier, P., Ducreux, M., Armand, J.P. Phase I and pharmacokinetic study of DX-8915f, a novel topoisomerase inhibitor, using a 30-minute infusion every 3 weeks. 10th NCI-EORTC Symp New Drugs Cancer Ther (June 16-19, Amsterdam) 1998, Abst 248.
32. Johnson, T., Geyer, C., De Jager, R., Eckhardt, S., Smetzer, L., Clark, G., Coyle, J., Drengler, R., Von Hoff, D., Rowinsky, E. A phase I and pharmacokinetic (PK) study of DX-8951f, a novel hexacyclic camptothecin (CPT) analog, on a 30 minute infusion daily for 5 days every 3 week schedule. 10th NCI-EORTC Symp New Drugs Cancer Ther (June 16-19, Amsterdam) 1998, Abst 245.
33. Johnson, T., Geyer, C., De Jager, R., Eckhardt, S., Smetzer, L., Coyle, J., Drengler, R., Von Hoff, D., Rowinsky, E. Phase I and pharmacokinetic (PK) study of DX-8951f, a novel hexacyclic camptothecin analog, on a 30 minute infusion daily for 5 days every 3 week schedule. Proc Am Soc Clin Oncol 1998, 17: Abst 756.
34. Rowinsky, E., Johnson, T., Geyer, C., Eckhardt, S., Smetzer, L., Coyle, J., Drengler, R., Diab, S., De Jager, R., Von Hoff, D. DX-8951f, a hexacyclic camptothecin (CPT) analog on a daily x 5 day schedule: A phase I and pharmacokinetic (PK) study. Proc Am Soc Clin Oncol 1999, 18: Abst 632.
35. Garrison, M.A., Hammond, L.A., Geyer, C.E. Jr. et al. A phase I and pharmacokinetic study of exatecan mesylate administered as a protracted 21-day infusion in patients with advanced solid malignancies. Clin Cancer Res 2003, 9: 2527-37.
36. Garrison, M., Hammond, L.A., Geyer, C. et al. A phase I and pharmacokinetic study of camptothecin (CPT) analog (exatecan mesylate): Escalating infusion duration and dose. Proc Am Soc Clin Oncol 2000, 19: Abst 765.
37. Talbot, D.C., Boven, E., Dobbs, N., Varcoe, S., Ruijter, R., Fraser, S. Phase I and pharmacokinetic study of DX-8915f, a novel topoisomerase I inhibitor, using a 30 minute infusion weekly x 3 every 4 weeks. 10th NCI-EORTC Symp New Drugs Cancer Ther (June 16-19, Amsterdam) 1998, Abst 247.
38. Minami, H., Sasaki, Y., Shigeoka, Y., Onozawa, Y., Fujii, H., Igarashi, T., Itoh, K., Tamanoi, K., Kajimura, T., Oguma, T. Phase I study and pharmacology of DX-8951f, a new camptothecin derivative, infused over 30 minutes every three weeks. AACR-NCI-EORTC Int Conf Mol Targets Cancer Ther (Nov 16-19, Washington DC) 1999, Abst 326.
39. Minami, H., Sasaki, Y., Onozawa, H., Ohtsu, T., Igarashi, T., Itoh, K., Tamanoi, K., Oguma, T. Phase I study and clinical pharmacology of DX8951f, a new camptothecin derivative, infused over 30 minutes every three weeks. Proc Am Soc Clin Oncol 1999, 18: Abst 685.
40. Boige, V., Raymond, E., Gatineau, M., Faivre, S., Meely, K., Mekhaldi, S., Pautier, P., Ducreux, M., Escudier, B., Armand, J.P. Final results of a phase I and pharmacokinetic study of DX-8951f in patients with advanced tumors. Proc Am Assoc Cancer Res 1999, 40: Abst 754.
41. Kamiya, Y., Yamamoto, N., Yamada, Y., Kusaba, H., Shimada, Y., Tamura, T., Tamanoi, K., Oguma, T. Phase I and pharmacokinetic (PK) study of DX-8951f, a novel camptothecin analog, given as a 30 minute infusion daily for 5 days. AACR-NCI-EORTC Int Conf Mol Targets Cancer Ther (Nov 16-19, Washington DC) 1999, Abst 327.
42. Kamiya, Y., Yamamoto, N., Tamura, T., Shimada, Y., Oguma, T. Phase I and pharmacokinetic study of DX-8951f, a novel camptothecin analog, given as a 30-minute infusion daily for 5 days. Proc Am Soc Clin Oncol 1999, 18: Abst 832.
43. Giles, F.J., Cortes, J.E., Thomas, D.A., DeJager, R., Garcia-Manero, G., Jeha, S., Kantarjian, H.M. Phase I study of exatecan mesylate (DX-8951f), a novel topoisomerase I (topo I) inhibitor. Blood 2000, 96(11, Part 1): Abst 519.
44. Jeha, S., Kantarjian, H., Cortes, J.E., DeJager, R., Bivins, C., Grigsby, V., Giles, F. Leukemia phase I study of DX-8951f, a novel topoisomerase I (topo I) inhibitor. Proc Am Soc Clin Oncol 2000, 19: Abst 55.
45. O'Reilly, E.M., Lenzi, R., Mani, S., Schwartz, G.K., Sharma, S., Keisen, D.P., Levin, A., Danna, M., Bridget, H., De Jager, R. Final results of a phase I study of DX-8951f (DX) and gemcitabine (Gem) in advanced solid tumor malignancies. Proc Am Soc Clin Oncol 2002, 21 (Part 1): Abst 394.
46. O'Reilly, E.M., Hoff, P.M., Mani, S., Schwartz, G.K., Aird, S., Sharma, S., Hazelwood, B., Kelvin, J., De Jager, R., Kelsen, D. A phase I study of DX-8951f (exatecan mesylate, DX) and gemcitabine (Gem) in advanced solid tumors. Proc Am Soc Clin Oncol 2001, 20: Abst 412.
47. Trippett, T., Furman, W., Aquino, V. et al. Phase I study of DX-8951f in pediatric patients with advanced solid tumors. Proc Am Soc Clin Oncol 2001, 20(Part 1): Abst 1500.
48. Royce, M., Saltz, L., Rowinsky, E.K., Hoff, P.M., Geyer, C.E. Jr., Dumas, P., Lassere, Y.M., Coyle, J., De Jager, R., Pazdur, R. A phase II study of intravenous exatecan mesylate (DX-8951f) administered daily for five days every three weeks to patients with advanced or metastatic adenocarcinoma of the colon or rectum. Proc Am Soc Clin Oncol 2000, 19: Abst 1129.
49. Talbot, D.C., White, S., Jones, P., Thatcher, N.N., Mattson, K., Meely, K., Cheverton, P. Phase II study of exatecan mesylate (DX-8951f) in advanced NSCLC. Proc Am Soc Clin Oncol 2000, 19: Abst 2166.
50. Esteva, F.J., Rivera, E., Cristofanilli, M., Valero, V., Royce, M., Duggal, A., Colucci, P., DeJager, R., Hortobagyi, G.N. A phase II study of intravenous exatecan mesylate (DX-8915f) administered daily for 5 days every 3 weeks to patients with metastatic breast carcinoma. Cancer 2003, 98: 900-7.
51. Esteva, F.J., Rivera, E., Cristofanilli, M., Valero, V., Boutte, T., Royce, M., Duggal, A., Colucci, P., Dejager, R., Hortobagyi, G.N. A phase II study of intravenous exatecan mesylate (DX-8915f) administered daily for five days every three weeks to patients with metastatic breast cancer. Proc Am Soc Clin Oncol 2003, 22: Abst 67.
52. Kudelka, A., Verschraegen, C.F., Vincent, M., Levenback, C., Wolf, J., Bevers, M., Loyer, E., Brown, N., Kavanagh, J.J. Phase II study of intravenous DX-8951f in patients with advanced ovarian, tubal, or peritoneal cancer refractory to platinum, taxane, and topotecan. Proc Am Soc Clin Oncol 2000, 19: Abst 1550.
53. Calvert, P., Jayson, G., Atkinson, R., Ganesan, T., Cervantes-Ruiperez, A., Vasey, P., Adams, M., Boven, E., Calvert, A.H., Cheverton, P. Phase II clinical and pharmacokinetic study of exatecan mesylate (DX-8951f) in patients with advanced ovarian cancer, refractory to, or relapsed after platinum and taxane. Ann Oncol 2000, 11 (Suppl. 4): Abst 372P.
54. O'Reilly, E., Hammond, L., Donehower, R., Schwartz, G., Kelvin, J., Aird, S., Sharma, S., Schrag, D., Molloy, K., De Jager, R. A phase II study of exatecan mesylate (DX-8951f) in advanced pancreatic cancer. Ann Oncol 2000, 11 (Suppl. 4): Abst 2770.
55. O'Reilly, E.M., Hammond, L., Sharma, S., Aird, S., Rowinsky, E.K., Kelvin, J., Kelsen, D.P., Ochoa, L., Zitelli, A., De Jager, R.L. A phase II study of exatecan mesylate (DX-8915f, DX) in advanced pancreatic cancer. Proc Am Soc Clin Oncol 2000, 19: Abst 1170.
56. D'Adamo, D., Hammond, L., Donehower, R., Sharma, S., Aird, S., Kelsen, D.P., Ochoa, L., Rowinsky, E., De Jager, R. O'Reilly, E.M. Final results of a phase II study of DX-8951f (exatecan mesylate, DX) in advanced pancreatic cancer. Proc Am Soc Clin Oncol 2001, 20(Part 1): Abst 532.
57. Brown, T.D., Patt, Y., Rowinsky, E.K. et al. A phase II study of intravenous DX-8951f (exatecan mesylate) administered daily for five days every three weeks to patients with hepatocellular carcinoma. Proc Am Soc Clin Oncol 2001, 20(Part 2): Abst 2345.
58. Abou-Alfa, G.K., O'Reilly, E.M., Rowinsky, E.K. et al. Final results of a phase II study of DX-8951f (DX, exatecan mesylate) in biliary tree cancers. Proc Am Soc Clin Oncol 2002, 20(Part 1): Abst 561.