Camptothecin antitumor agents

IDrugs

Volumn 2, Issue 9, 1999, Pages 896-906

  Lerchen, Hans Georg ^a   Bayer, A G ^a  

^a Central Research Bunding   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

9 AMINOCAMPTOTHECIN; BELOTECAN; CAMPTOTHECIN; CARBOPLATIN; CISPLATIN; DNA TOPOISOMERASE; DOXORUBICIN; ETOPOSIDE; EXATECAN; FLUOROURACIL; HAR 7; HOMOCAMPTOTHECIN; IRINOTECAN; KARENITECIN; LURTOTECAN; MACROGOL; PACLITAXEL; POLY[N (2 HYDROXYPROPYL)METHACRYLAMIDE]; RUBITECAN; TOPOTECAN; UNCLASSIFIED DRUG;

ANEMIA; BONE MARROW SUPPRESSION; BREAST CANCER; CANCER; CLINICAL TRIAL; COLORECTAL CANCER; CONTROLLED CLINICAL TRIAL; DNA REPLICATION; DRUG INHIBITION; DRUG MECHANISM; DRUG RESEARCH; GASTROINTESTINAL TOXICITY; HEAD AND NECK CANCER; HUMAN; LUNG SMALL CELL CANCER; NEUTROPENIA; NONHODGKIN LYMPHOMA; NONHUMAN; OVARY CANCER; OVARY METASTASIS; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; RANDOMIZED CONTROLLED TRIAL; REVIEW; SKIN CANCER; THROMBOCYTOPENIA; UTERINE CERVIX CANCER;

EID: 0032863833     PISSN: 13697056     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (113)

1. Wall ME, Wani MC, Cook CE, Palmer KH, McPhail AT. Sim GA: Plant antitumor agents. I. The isolation and structure of camptothecin, a novel alkaloidal leukemia and tumor inhibitor from Camptotheca acuminate. J Am Chetn Soc (1966)88:3888-3890.
2. First report of the discovery of camptothecin.
3. Gottlieb JA, Guarino AM, Call JB, Oliverio VT, Block JB: Preliminary pharmacologie and clinical evaluation of camptothecin sodium (NSC-100880). Cancer Chernother Rep (1970) 54:461-479.
4. Moertel CG, Schutt AJ, Reitemeier RJ, Hahn RG: Phase II study of camptothecin (NSC-100880) In the treatment of advanced gastrointestinal cancer. Cancer Chemother Rep (1972)56:95-101.
5. Gottlieb JA, Luce JK: Treatment of malignant lymphoma with camptothecin (NSC-100880). Cancer Chemother Rep (1972)56:103-105.
6. Wall ME, Wani MC: Antineoplastic agents from plants. Annu Rev Pharmaco! Toxicol (1977) 17:117-132.
7. Wani MC, Ronman PE, Undley JT, Wall ME: Plant antitumor agents. 18. Synthesis and biological activity of camptothecin analogs. J Med Chem (1980) 23:554-560.
8. Wani MC, Nicholas AW, Wall ME: Plant antitumor agents. 23. Synthesis and antileukemic activity of camptothecin analogs. J Med Chem (1986) 29:2358-2363.
9. SARs ofA-ring modifications leading to highly potent analogs.
10. Jaxel C, Kohn KW, Wani MC, Wall ME: Structure activity study of the actions of camptothecin derivatives on mammalian topoisomerase I, evidence for a specific receptor site and for a relation to antitumor activity. Cancer Res (1989) 49:1465-1469.
11. Verification of earlier observed in vivo SARs at the molecular target (see [11]).
12. Hsiang YH, Hertzberg R, Hecht S, Uu LF: Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. JBiol Chem (1985) 260:14873-14878.
13. First report of the molecular target of camptothecin.
14. Hsiang YH, Liu LF: Identification of mammalian DNA topoisomerase I as an intracellular target of the anticancer drug camptothecin. Cancer Res (1988) 48:1722-1726.
15. More comprehensive investigations on mechanism of action is presented.
16. Hsiang YH, Uu LF. Wall ME, Wani MC, Nicholas AW, Manikumar G, Kirschenbaum S, Silber R, Potmesil M: DNA topoisomerase 1-fnediated DNA cleavage and cytotoxicity of camptothecin analogues. Cancer Res (1989) 49:4385-4389.
17. Verification of earlier observed in vivo SARs at the molecular target (see [8]).
18. Zhang H, D'Arpa P, Uu LF: A model for tumor cell killing by topoisomerase poisons. Cancer Cells (1990) 2:23-27.
19. Wall ME, Wani MC: Camptothecin and analogs: From discovery to clinic In: Camptothecins: New Anticancer Agents Potmesil M, Pinedo H (Eds), CRC Press, Boca Raton, Ann Arbor, London, Tokyo (1995):21-41.
20. Comprehensive review of SAR of extracted and synthetic camptothecin compounds.
21. Sawada S, Okajima S, Aiyarna R, Nokata K, Furuta T, Yokokura T, Sugino E, Yamaguchi K, Miyasaka T: Synthesis and antitumor activity of 20(S)-camptothecin derivatives: Carbamate-linked, water soluble derivatives of 7-ethy!-10-hydroxycamptothecin. Chem Pharm Bull (1991) 39(6):1446-1454.
22. Description of synthesis and preclinical activity of CPT-11.
23. Kingsbury WD, Boehm JC, Jakas DR, Holden KG. Hecht SM. Gallagher G, Caranfa MJ, McCabe FL, Faucette LF, Johnson KJ, Hertzberg RP: Synthesis of water-soluble (amlnoalky)camptothecin analogues: Inhibition of topoisomerase I and antitumor activity. J Med Chem (1991) 34:98-107.
24. Description of selection, synthesis and preclinical activity of topotecan.
25. Kawato Y, Furuta T, Aonuma M, Yasuoka M, Yokokura T Matsumoto K: Antitumor activity of a camptothecin derivative, CPT-11, against human tumor xenografts in nude mice. Cancer Chemother Pharmacol ( 1991) 28:192-198.
26. Comparison of antitumor activity of CPT-11, SN-38 and other cytotoxics.
27. Giovanella BC, Hinz HR, Kozielski AJ, Stehlin JS, Silber R, Potmesil M: Complete growth inhibition of human cancer xenografts in nude mice by treatment with 20-(S)camptothecin. Cancer Res (1991) 51:3052-3055.
28. Burke TG, Mi Z: Preferential binding of the carboxylate form of camptothecin by human serum albumin. Anal Biochem (1993) 212:285-287
29. First publication of this important finding.
30. Liehr JG, Ahmed AE, Giovanella BC: Pharmacokinetics of camptothecins administered orally. In: The camptothecins: from discovery to the patient. Ann NY Acad Sei (1996) 803:157-163.
31. Wall ME, Wani MC, Nicholas AW, Manikumar G, Tele C, Moore L, Truesdale A, Leitner P, Besterman JM: Plant antitumor agents. 30. Synthesis and structure activity of novel camptothecin analogs. J Med Chem (1993) 36:26892700.
32. Hertzberg RP, Caranfa MJ, Holden KG, Jakas DR, Gallagher G, Mattem MR, Mong SM, Bartus JO, Johnson, RK, Kingsbury WD: Modification of the hydroxy lactone ring of camptothecin: Inhibition of mammalian topoisomerase I and biological activity. JMed Chem (1989) 32:715-720.
33. Lackey K, Besterman JM, Fletcher W, Leitner P, Morton B, Stembach D: Rigid analogs of camptothecin as DNA topoisomerase inhibitors. J Med Chem (1995) 38:906-911.
34. Fan Y, Weinstein JN, Kohn KW, Shi LM, Pommmier Y: Molecular modeling studies of the DNA-topoisomerase I ternary cleavable complex with camptothecin. J Med Chem (1998)41:2216-2226.
35. Redinbo MR, Stewart L, Kühn P, Champoux JJ, Hol WGJ: Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA. Science (1998) 279:1504-1513.
36. Paper gives an excellent insight into mechanism of action of camptothecins.
37. Fassberg J, Stella VJ: A kinetic and mechanistic study of the hydrolysis of camptothecin and some analogs. J Pharm Sc/(1992) 120:2979-2980.
38. Burke TG: Chemistry of the camptothecins in the blood stream; drug stabilization and optimization of activity. In: The camptothecins: from discovery to the patient. Ann NY Acad Sei (1996) 803:29-31.
39. Compact review indicating the most important references.
40. Wamer DL, Burke TG: Comparison of filter and tunable fluorescence detection for the HPLC simultaneous quantitation of lactone and carboxylate forms of topotecan in plasma. J LJq Chromatogr Relat Technol (1997) 20(10):1523-1537.
41. Rivory LP, Robert J: Reversed-phase high performance liquid Chromatographie method for the simultaneous quantitation of the carboxylate and lactone forms of the camptothecin derivative Irinotecan, CPT-11, and its metabolite SN38 in plasma. J Chromatogr B (1994) 661:133-141.
42. Herben VMM, Mazee D, Van Gortel-Van Zomeren DM, Zeedijk S, Rosing H, Schellens JHM, Huinik WW, Ten Bokkel, Beijnen JH: Sensitive determination of the carboxylate and lactone forms of the novel antitumor drug irinotecan and its active metabolite in plasma by HPLC. J LJq Chromatogr Relat Technol (1998) 21(10):1541-1558.
43. Yang D. Strode JT. Spielman HP, Wang AHJ, Burke TG: DNA interactions of two clinical camptothecin drugs stabilize their active lactone forms. J Am Chem Soc (1998) 120:2979-2980.
44. Chourpa, I, Riou JF, Millot JM, Pommier Y, Manfait M: Modulation in kinetics of lactone ring hydrolysis of camptothecins upon interaction with topoisomerase I cleavage sites on DNA. Biochemistry (1998) 37(20):7284-7291.
45. Dancey J, EA Eisenhauer: Current perspectives on camptothecins in cancer treatment. Br J Cancer (1996) 74:327-338.
46. Excellent and compact review summarizing clinical trials and perspectives of the most important compounds.
47. Slichenmyer WJ, Donehower RC: Recent clinical advances with camptothecin analogs. Cancer Treat Res (1995) 78:29-43.
48. Arbuck SG, Blaylock BA, Christian MC, Parkinson DR, Takimoto CH: The camptothecin topoisomerase I inhibitors: an update. Prog Anti-Cancer Chemother (1997) 3-27.
49. Comprehensive review with a particular focus on clinical aspects of irinotecan and topotecan.
50. Kaneda N, Nagata H, Furuta T, Yokokura T: Metabolism and pharmacokinetics of the camptothecin analogue CPT-11 in the mouse. Cancer Res (1990) 50:1715-1720.
51. Bissery MC, Vrignaud P, Lavelle F, Chabot GG: Preclinical antitumor activity and pharmacokinetics of irinotecan (CPT-11) in tumor-bearing mice In: The Camptothecins; From discovery to the patient. Ann NY Acad Sei (1996) 803:173-180.
52. Rothenberg, ML: CPT-11: An original spectrum of clinical activity. Semin Onco/(1996) 23(1, Suppl 3):21-26.
53. Saijo N: Clinical trials of Irinotecan hydrochloride (CPT, Campto Injection, Topotecin Injection) in Japan In: The amptothecins; from discovery to the patient. Ann NY Acad Sei (1996)803:292-305.
54. Takasuna K, Hagiwara T, HirohshiM, Kato M, Nomura M, Nagai E, Yokoi T, Kamataki T: Involvement of β-glucuronidase in intestinal microflora in the intestinal toxicity of the antitumor camptothecin derivative Irinotecan hydrochloride (CPT-11) in rats. Cancer Res (1996) 56:3752-3757.
55. lyer L, Ratain M: Clinical pharmacology of camptothecins. Cancer Chemother Pharmacol (1998) 42(Suppl):S31 -S43.
56. Boisseau M, Guichard S, Canal P, Bugat R: Irinotecan (CPT11): current status and perspectives. Exp Opin Invest Drugs (1996) 5(6):613-628.
57. Skirvin JA, Relias V: Topoisomerase I inhibitors: 2. Irinotecan. J Oncol Pharm Pract (1998) 4(2):103-116.
58. Comprehensive review on clinical aspects of irinotecan.
59. Houghton PJ, Cheshire PJ, Hallman JD, Lutz L, Friedman HS, Danks MK, Houghton JA: Efficacy of topoisomerase I inhibitors, topotecan and irinotecan, administered at low dose levels In protected schedules to mice bearing xenografts of human tumors. Cancer Chemother Pharmacol (1995)36:393-403.
60. Bolis G, Malmstrom H, Coleman R, Relds SC, Heran JF, Hudson I, Broom C, Scarabelli C, Davidson N, Spanczynski M: Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer. J Clin Oncol (1997), 15(6):2183-. 2193.
61. Rowinsky EK, Kaufmann SH: Topotecan in combination chemotherapy. Semin Oncol (1997) 24(6 Suppl 20):S20/11-S20/26.
62. 'Relias V, Skirvin JA: Topoisomerase I inhibitors: 1. Topotecan. J Oncol Pharm Pract (1997) 3(4):173-185.
63. Carmichae! J, Ozols RF: Topotecan, an active new antineoplastic agent: review and current status. Exp Opin Invest Drugs (1997) 6(5):593-608.
64. Comprehensive review on preclinical and clinical aspects and perspectives.
65. Giovanella, BC, Stehlin JS. Wall ME, Wani MC, Nicholas AW, Liu LF, Silber R, Potmesil M: DNA topoisomerase l-targeted chemotherapy of human colon cancer in xenografts. Science (1989) 246:1046-1048.
66. Potmesil M, Arbuck SG, Takimoto CH, Liebes L, Höchster H: 9Aminocamptothecin and beyond: Preclinical and clinical studies. Ann NYAcad Sei (1996) 803:231-246.
67. Natelson EA, Giovanella BC, Verschraegen CF, Fehir KM, De Ipolyi PD, Harris N, Stehlin JS: Phase I clinical and pharmacological studies of 20(S)-camptothecin and 20(S}9-nitrocamptothecin as anticancer agents. Ann NY Acad Sc (1996)803:224-230.
68. Emerson DL, Besterman JM, Brown HR, Evans MG, Leitner PP, Luzzio MJ, Shaffer JE, Stembach DD, Uehling D, Yuong A: In vivo antitumor activity of two seven-substituted watersoluble camptothecin analogs. Cancer Res (1995) 55:603609.
69. Emerson DL, Amirgahari N, Bendele R, Brown E, Chen LS, Chiang SM, Gill S, Leray JD, Moynihan K, Tomkinson B, Luzzio MJ: NX-211, a liposomal formulation of lurtotecan demonstrates enhanced pharmacokinetic and antitumor activity. ProcAmAssoc Cancer Res (1998) 39:278. 53. Mitsui I, Kumazawa E, Hirota Y, Aonuma M, Sugimori M, Ohsuki S, Uoto K, Ejima A, Terasawa H, Sato K: A new watersoluble camptothecin derivative, DX-8951f, exhibits antitumor activity against human tumors in vitro and in vivo. Jpn J Cancer Res. (1995) 86:776-782.
70. Kumazawa E, Jimbo T, Ochi Y: Potent and broad antitumor effects of DX-8951f, a water-soluble camptothecin derivative, against various human tumors xenografted in nude mice. Cancer Chemother Pharmacol ( 1998) 42:210-220.
71. Extended comparison of DX-8951 with other topisomerase I inhibitors.
72. Kumazawa E, Tohgo A: Antitumor activity of DX-8951 f: a new anticancer derivative. Exp Opin Invest Drugs (1998) 7(4):625-632.
73. Royce M, Hoff PM, Brito R: Phase I trial of DX-8951 f, a novel camptothecin analog, administered by a 24-hour continous infusion. Proc Am Soc Clin Oncol (1998) 34:757
74. Hausheer F, Haridas K, Zhao M, Murali D, Seetharamulu P, Yao S, Reddy D, Pavankumar P, Wu M, Saxe J, Huang Q, Rustum Y: Karenitecins (part II): A novel class of orally active highly lipophilic topoisomerase I inhibitors. Proc Am Assoc Cancer Res (1998) 39:420.
75. Jew S, Kim MG, Kim HJ, Roh EY, Cho Y, Kim JK, Cha KH, Lee KK, Man HJ, Choi JY, Lee H: Synthesis and antitumor activity of 7-substituted 20(RS)-camptothecIn analogues.
76. Bioorg Med Chem Lett (1996) 6(7):845-848.
77. Lee JH. Sohn YS, Lee JM, Kim KK, Kim JK, Ahn SK, Jew SS, Park JG, Hong CI: Antitumor activities of CKD602, a novel camptothecin derivative. Proc Am Assoc Cancer Res (1998) 39:303.
78. Lavergne O, Lesueur-Ginot L, Rodas FP, Bigg DCH: BN 80245: An E-ring modified camptothecin with potent antiproliferative and topoisomerase I inhibitory activities. Bioorg Med Chem Lett (1997) 7(17):2235-2238.
79. New aspects of SARs in the pharmacophore unit of camptothecin derivatives.
80. Kasprzyk PG, Lesueur-Ginot L, Dermaquay D, Carlson M, Lauer J, Lavergne O, Bigg DCH: A series of E-ring modified camptothecins display potent topoisomerase I mediated antiproliferative activity in vitro and in vivo. Proc Am Assoc Cancer Res (1998) 39:420.
81. Chou TC, Bom D, Zheng YH, Josien H, Zimmer S, Burke TG, Curran D: 7-Silylcamptothecins (Silatecans): a new class of lipophilic camptothecins highly active against human cancers in vitro and in vivo. Proc Am Assoc Cancer Res (1998)39:223.
82. Josien H, Bom D, Curran D, Zheng YH, Chou TC: 7Silylcamptothecins- (Silatecans): a new family of camptothecin antitumor agents. Bioorg Med Chem Lett (1997) 7(24):3189-3194.
83. Bedeschi A, Candiani I, Geroni C, Capolongo L: Water-soluble camptothecin derivatives. Drugs Future (1997) 22(11):12591266.
84. Vishnuvajjala BR, Cradock JC, Garzon-Aburbeh A: Water soluble camptothecin prodrugs. Pharm Res (1986) 3(5):22S.
85. Cao C, Harris N, Kozielski A, Vardeman D, Slehlin JS, Giovanella B: Alkyl esters of camptothecin and 9nitrocamptothecin: Synthesis, In vitro pharmacokinetics, toxicity and antitumor activity. J Med Chem (1998) 41:31-37.
86. Duncan R, Spreafico F: Polymer conjugates: Pharmacokinetic considerations for design and development. Clin Pharmacokinet (1994) 27(4):290-306. xcellent review about the rationale of polymeric drug delivery systems.
87. Maeda H, Matsumura Y: Tumoritropic and lymphotropic principles of macromolecular drugs. Crit Rev Ther Drug CarrierS/(1989) 6:193-210.
88. Greenwald RB, Pendri A, Conover C, Gilbert C, Yang R, Xia J: Drug Delivery systems: 2. camptothecin 20-O-poly(ethylene glycol) ester transport forms. J Med Chem (1996)39:1938-1940.
89. Greenwald RB, Pendri A, Conover C, Lee C, Choe YH, Gilbert C, Martinez A, Xia J, Wu D, Hsue M: Camptothecin-20-PEG ester transport forms: the effect of spacer groups on antitumor activity. Bioorg Med Chem Lett (1998) 6:551-562.
90. Caiolfa VR, Frigerio E, Castelii MG, Poggesi I, Fiorino A, Marsiglio A, Lovisolo PP, Farao M, Sola F, Pesenti E, Zamai M, Angelucci F, Suarato A: HMPA-based tumor delivery: pharmacokinetics and tumor delivery of the first MAG-prteleu-gly-CPT soluble derivative. Proc Am Assoc Cancer Res (1998)39:429.
91. Sadzuka Y, Hirotsu S, Miyagishima A, Nozawa Y, Hirota S): The study of polyethylene glycol-coated liposomes containing CPT-11. J Liposome Res (1997) 7(2&3):241 -260.
92. Sugarman SM, Zou Y, Wasan K, Piorot K, Kumi R, Reddy S, 1 Perez-Soler R: Lipid-complexed camptothecin: Formulation and initial biodistribution and antitumor studies. Cancer Chemother Pharmacol (1996) 37(6):531 -538.
93. Thompson J, Slewart CFi Houghton, PJ: Animal models for studying the action of topoisomerase I targeted drugs. Biochim Biophys Acta (1998) 1400(1 -3):301 -319.
94. BIONUMERIK PHARMACEUTICALS INC (Hausheer F, Haridas K, Seetharamulu P, Murali D, Reddy D, Yao S, Pelluru P): Highly lipophilic camptothecin derivatives. WO-09807727 (1998).
95. BIONUMERIK PHARMACEUTICALS INC (Hausheer FH, Murali D, Haridas K, Reddy DG): Pharmaceutical formulations of highly lipophilic camptothecin derivatives in N-methylpyrrolidin-2-one. WO-09639143 (1996).
96. SOCIETE DE CONSEILS DE RECHERCHES ET D'APPLICATIONS SCIENTIFIQUES (Bigg D, Lavergne O, Pla Rodas F, Pommier J, Ulibarri, G): Novel camptothecin analogues, préparation methods therefor, use therof as drugs and pharmaceutical compositions containing said analogs. WO-09700876 (1997). Related application from the same group in this field: WO-09828305.
97. SOCIETE DE CONSEILS'DE RECHERCHES ET D'APPLICATIONS SCIENTIFIQUES (Bigg D, Lavergne O, Hamett J, Rolland A, Liberalere AM, Lanco C): Prodrugs and counterparts of camptothecin, their applications as medicines. WO-09828304 (1998).
98. PHARMACIA SPA (Bedeschi A, Zarini F, Cabri W, Candiani I, Penco S, Capolongo L): Water-soluble camptothecin derivatives. WO-09522549 (1995).
99. Further related applications by Pharmacia & Upjohn in this field: WO-09637496, WO-09728164, WO-09725332, WO-09835969.
100. DR REDDY'S FOUNDATION/REDDY-CHEMINOR INC (Duwuri S, Akella V, Vedula S, Kalla R, Akella S): Novel water-soluble analogs of 20(S)-camptothecin WO-09746564 (1997).
101. Further applications from the same group in this field: WO-09746563, WO-09746562.
102. THE UNIVERSITY OF MICHIGAN (Shull BK, Slemon C, Koreeda M): Glycosylated analogs of camptothecin WO-09634003 (1996).
103. THE UNITED STATES OF AMERICA REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (Vishnuvajjala BR. Garzon-Aburbeh A): Water soluble prodrugs of camptothecin. US-04943579 (1990).
104. RESEARCH TRIANGLE INSTITUTE (Wall ME, Wani MC): Water-soluble esters of camptothecin compounds. WO-09602546 (1996).
105. BAYER AKTIENGESELLSCHAFT (Lerchen HG, von dem Bruch K, Pelersen U, Baumgarten J, Fiel N, Antonicek HP, Weichel W, Sperzel M, Bremm KD): Sugar-modified cytostatics. WO-09631532 (1996).
106. Related applications from the same group in this field: WO-09814459 (1998), WO-09814468 (1998), WO-09815573 (1998), WO-09851703 (1998).
107. STEHLIN FOUNDATION FOR CANCER RESEARCH (Zhisong C, Giovanella B): Derivatives of camptothecin for use in treating cancer. US-05731316 (1998).
108. ENZON INC (Greenwald RB, Pendri A, Zhao H): High molecular weight polymer-based prodrugs. WO-09807713 (1998).
109. Related applications from the same group in this field: WO-09623794 (1996).
110. PHARMACIA & UPJOHN (Angelucci F, Suarato A): New conjugate of camptothecin with methacrylamide copolymer used as topoisomerase I inhibiting antitumor agent with low toxicity and high water solubility. WO-09510304 (1995).
111. BIONUMERIK PHARMACEUTICALS INC (Hausheer FH, Haridas K): Lactone stable formulation of 7-ethyl-10hydroxycamptothecin. US-0567/4874 (1997).
112. OHIO STATE UNIVERSITY (Burke'TG): Liposomal and micellar stabilization of camptotheciri drugs. US-05552156 (1996).
113. MATRIX PHARMACEUTICALS INC (Jones RE, Washco K, Trager G, Roskos KV, Maskiewicz R): Gel delivery vehicles for anticellular proliferative agents. WO-09836776 (1998).