Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
editorial
. 1996 Aug;74(3):327–338. doi: 10.1038/bjc.1996.362

Current perspectives on camptothecins in cancer treatment.

J Dancey, E A Eisenhauer
PMCID: PMC2074644  PMID: 8695345

Abstract

The camptothecins are a new class of chemotherapeutic agents which have a novel mechanism of action targeting the nuclear enzyme topoisomerase I. Knowledge of the structure-activity relationships of the parent compound camptothecin has led to the development of effective soluble analogues with manageable toxicities. Broad anti-tumour activity shown in preclinical studies has been confirmed in phase I/II studies for irinotecan and topotecan. Two other derivatives, 9-aminocamptothecin and GI 147211C, are undergoing phase I and early phase II evaluation. Although camptothecin is a plant extract, it and most of its derivatives are not affected by the classic P-gpMDR1 mechanism of resistance which may allow the development of novel combination chemotherapeutic regimens. Important areas of future endeavour will include the development of rational combination regimens and the pursuit of randomised trials. Based on single agent data, colorectal cancer and non-small-cell lung cancer should be the focus for future irinotecan studies. Small-cell lung cancer and ovarian carcinoma are logical tumour types to pursue with topotecan. Both 9-aminocamptothecin and GI 147211C are too early in their clinical evaluation to make recommendations about their future roles. Finally, the unfolding story of camptothecin analogue development will give important insights into the predictive value of preclinical observations on relative efficacy, schedule dependency, combination strategies and resistance mechanisms which have helped determine the strategies for clinical evaluation of these agents.

Full text

PDF
327

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abigerges D., Armand J. P., Chabot G. G., Da Costa L., Fadel E., Cote C., Hérait P., Gandia D. Irinotecan (CPT-11) high-dose escalation using intensive high-dose loperamide to control diarrhea. J Natl Cancer Inst. 1994 Mar 16;86(6):446–449. doi: 10.1093/jnci/86.6.446. [DOI] [PubMed] [Google Scholar]
  2. Abigerges D., Armand J. P., Chabot G. G., Da Costa L., Fadel E., Cote C., Hérait P., Gandia D. Irinotecan (CPT-11) high-dose escalation using intensive high-dose loperamide to control diarrhea. J Natl Cancer Inst. 1994 Mar 16;86(6):446–449. doi: 10.1093/jnci/86.6.446. [DOI] [PubMed] [Google Scholar]
  3. Andoh T., Ishii K., Suzuki Y., Ikegami Y., Kusunoki Y., Takemoto Y., Okada K. Characterization of a mammalian mutant with a camptothecin-resistant DNA topoisomerase I. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5565–5569. doi: 10.1073/pnas.84.16.5565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Andoh T., Ishii K., Suzuki Y., Ikegami Y., Kusunoki Y., Takemoto Y., Okada K. Characterization of a mammalian mutant with a camptothecin-resistant DNA topoisomerase I. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5565–5569. doi: 10.1073/pnas.84.16.5565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Araki E., Ishikawa M., Iigo M., Koide T., Itabashi M., Hoshi A. Relationship between development of diarrhea and the concentration of SN-38, an active metabolite of CPT-11, in the intestine and the blood plasma of athymic mice following intraperitoneal administration of CPT-11. Jpn J Cancer Res. 1993 Jun;84(6):697–702. doi: 10.1111/j.1349-7006.1993.tb02031.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Araki E., Ishikawa M., Iigo M., Koide T., Itabashi M., Hoshi A. Relationship between development of diarrhea and the concentration of SN-38, an active metabolite of CPT-11, in the intestine and the blood plasma of athymic mice following intraperitoneal administration of CPT-11. Jpn J Cancer Res. 1993 Jun;84(6):697–702. doi: 10.1111/j.1349-7006.1993.tb02031.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Benedetti P., Fiorani P., Capuani L., Wang J. C. Camptothecin resistance from a single mutation changing glycine 363 of human DNA topoisomerase I to cysteine. Cancer Res. 1993 Sep 15;53(18):4343–4348. [PubMed] [Google Scholar]
  8. Benedetti P., Fiorani P., Capuani L., Wang J. C. Camptothecin resistance from a single mutation changing glycine 363 of human DNA topoisomerase I to cysteine. Cancer Res. 1993 Sep 15;53(18):4343–4348. [PubMed] [Google Scholar]
  9. Bertrand R., O'Connor P. M., Kerrigan D., Pommier Y. Sequential administration of camptothecin and etoposide circumvents the antagonistic cytotoxicity of simultaneous drug administration in slowly growing human colon carcinoma HT-29 cells. Eur J Cancer. 1992;28A(4-5):743–748. doi: 10.1016/0959-8049(92)90107-d. [DOI] [PubMed] [Google Scholar]
  10. Bertrand R., O'Connor P. M., Kerrigan D., Pommier Y. Sequential administration of camptothecin and etoposide circumvents the antagonistic cytotoxicity of simultaneous drug administration in slowly growing human colon carcinoma HT-29 cells. Eur J Cancer. 1992;28A(4-5):743–748. doi: 10.1016/0959-8049(92)90107-d. [DOI] [PubMed] [Google Scholar]
  11. Blaney S. M., Balis F. M., Cole D. E., Craig C., Reid J. M., Ames M. M., Krailo M., Reaman G., Hammond D., Poplack D. G. Pediatric phase I trial and pharmacokinetic study of topotecan administered as a 24-hour continuous infusion. Cancer Res. 1993 Mar 1;53(5):1032–1036. [PubMed] [Google Scholar]
  12. Blaney S. M., Balis F. M., Cole D. E., Craig C., Reid J. M., Ames M. M., Krailo M., Reaman G., Hammond D., Poplack D. G. Pediatric phase I trial and pharmacokinetic study of topotecan administered as a 24-hour continuous infusion. Cancer Res. 1993 Mar 1;53(5):1032–1036. [PubMed] [Google Scholar]
  13. Burris H. A., 3rd, Awada A., Kuhn J. G., Eckardt J. R., Cobb P. W., Rinaldi D. A., Fields S., Smith L., Von Hoff D. D. Phase I and pharmacokinetic studies of topotecan administered as a 72 or 120 h continuous infusion. Anticancer Drugs. 1994 Aug;5(4):394–402. doi: 10.1097/00001813-199408000-00002. [DOI] [PubMed] [Google Scholar]
  14. Burris H. A., 3rd, Awada A., Kuhn J. G., Eckardt J. R., Cobb P. W., Rinaldi D. A., Fields S., Smith L., Von Hoff D. D. Phase I and pharmacokinetic studies of topotecan administered as a 72 or 120 h continuous infusion. Anticancer Drugs. 1994 Aug;5(4):394–402. doi: 10.1097/00001813-199408000-00002. [DOI] [PubMed] [Google Scholar]
  15. Burris H. A., 3rd, Hanauske A. R., Johnson R. K., Marshall M. H., Kuhn J. G., Hilsenbeck S. G., Von Hoff D. D. Activity of topotecan, a new topoisomerase I inhibitor, against human tumor colony-forming units in vitro. J Natl Cancer Inst. 1992 Dec 2;84(23):1816–1820. doi: 10.1093/jnci/84.23.1816. [DOI] [PubMed] [Google Scholar]
  16. Burris H. A., 3rd, Hanauske A. R., Johnson R. K., Marshall M. H., Kuhn J. G., Hilsenbeck S. G., Von Hoff D. D. Activity of topotecan, a new topoisomerase I inhibitor, against human tumor colony-forming units in vitro. J Natl Cancer Inst. 1992 Dec 2;84(23):1816–1820. doi: 10.1093/jnci/84.23.1816. [DOI] [PubMed] [Google Scholar]
  17. Champoux J. J. Evidence for an intermediate with a single-strand break in the reaction catalyzed by the DNA untwisting enzyme. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3488–3491. doi: 10.1073/pnas.73.10.3488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Champoux J. J. Evidence for an intermediate with a single-strand break in the reaction catalyzed by the DNA untwisting enzyme. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3488–3491. doi: 10.1073/pnas.73.10.3488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Chen A. Y., Yu C., Potmesil M., Wall M. E., Wani M. C., Liu L. F. Camptothecin overcomes MDR1-mediated resistance in human KB carcinoma cells. Cancer Res. 1991 Nov 15;51(22):6039–6044. [PubMed] [Google Scholar]
  20. Chen A. Y., Yu C., Potmesil M., Wall M. E., Wani M. C., Liu L. F. Camptothecin overcomes MDR1-mediated resistance in human KB carcinoma cells. Cancer Res. 1991 Nov 15;51(22):6039–6044. [PubMed] [Google Scholar]
  21. Del Bino G., Bruno S., Yi P. N., Darzynkiewicz Z. Apoptotic cell death triggered by camptothecin or teniposide. The cell cycle specificity and effects of ionizing radiation. Cell Prolif. 1992 Nov;25(6):537–548. doi: 10.1111/j.1365-2184.1992.tb01458.x. [DOI] [PubMed] [Google Scholar]
  22. Del Bino G., Bruno S., Yi P. N., Darzynkiewicz Z. Apoptotic cell death triggered by camptothecin or teniposide. The cell cycle specificity and effects of ionizing radiation. Cell Prolif. 1992 Nov;25(6):537–548. doi: 10.1111/j.1365-2184.1992.tb01458.x. [DOI] [PubMed] [Google Scholar]
  23. Del Bino G., Lassota P., Darzynkiewicz Z. The S-phase cytotoxicity of camptothecin. Exp Cell Res. 1991 Mar;193(1):27–35. doi: 10.1016/0014-4827(91)90534-2. [DOI] [PubMed] [Google Scholar]
  24. Del Bino G., Lassota P., Darzynkiewicz Z. The S-phase cytotoxicity of camptothecin. Exp Cell Res. 1991 Mar;193(1):27–35. doi: 10.1016/0014-4827(91)90534-2. [DOI] [PubMed] [Google Scholar]
  25. Emerson D. L., Besterman J. M., Brown H. R., Evans M. G., Leitner P. P., Luzzio M. J., Shaffer J. E., Sternbach D. D., Uehling D., Vuong A. In vivo antitumor activity of two new seven-substituted water-soluble camptothecin analogues. Cancer Res. 1995 Feb 1;55(3):603–609. [PubMed] [Google Scholar]
  26. Friedman H. S., Houghton P. J., Schold S. C., Keir S., Bigner D. D. Activity of 9-dimethylaminomethyl-10-hydroxycamptothecin against pediatric and adult central nervous system tumor xenografts. Cancer Chemother Pharmacol. 1994;34(2):171–174. doi: 10.1007/BF00685936. [DOI] [PubMed] [Google Scholar]
  27. Fukuoka M., Negoro S., Niitani H., Furue H., Hasegawa K., Hara Y., Hara N., Taguchi T. [A phase I study of weekly administration of CPT-11 in lung cancer]. Gan To Kagaku Ryoho. 1990 May;17(5):993–997. [PubMed] [Google Scholar]
  28. Fukuoka M., Niitani H., Suzuki A., Motomiya M., Hasegawa K., Nishiwaki Y., Kuriyama T., Ariyoshi Y., Negoro S., Masuda N. A phase II study of CPT-11, a new derivative of camptothecin, for previously untreated non-small-cell lung cancer. J Clin Oncol. 1992 Jan;10(1):16–20. doi: 10.1200/JCO.1992.10.1.16. [DOI] [PubMed] [Google Scholar]
  29. Furuta T., Yokokura T. [Effect of administration schedules on the antitumor activity of CPT-11, a camptothecin derivative]. Gan To Kagaku Ryoho. 1990 Jan;17(1):121–130. [PubMed] [Google Scholar]
  30. Futatsuki K., Wakui A., Nakao I., Sakata Y., Kambe M., Shimada Y., Yoshino M., Taguchi T., Ogawa N. [Late phase II study of irinotecan hydrochloride (CPT-11) in advanced gastric cancer. CPT-11 Gastrointestinal Cancer Study Group]. Gan To Kagaku Ryoho. 1994 Jun;21(7):1033–1038. [PubMed] [Google Scholar]
  31. Gandia D., Abigerges D., Armand J. P., Chabot G., Da Costa L., De Forni M., Mathieu-Boue A., Herait P. CPT-11-induced cholinergic effects in cancer patients. J Clin Oncol. 1993 Jan;11(1):196–197. doi: 10.1200/JCO.1993.11.1.196. [DOI] [PubMed] [Google Scholar]
  32. Giovanella B. C., Hinz H. R., Kozielski A. J., Stehlin J. S., Jr, Silber R., Potmesil M. Complete growth inhibition of human cancer xenografts in nude mice by treatment with 20-(S)-camptothecin. Cancer Res. 1991 Jun 1;51(11):3052–3055. [PubMed] [Google Scholar]
  33. Giovanella B. C., Stehlin J. S., Wall M. E., Wani M. C., Nicholas A. W., Liu L. F., Silber R., Potmesil M. DNA topoisomerase I--targeted chemotherapy of human colon cancer in xenografts. Science. 1989 Nov 24;246(4933):1046–1048. doi: 10.1126/science.2555920. [DOI] [PubMed] [Google Scholar]
  34. Gong J., Li X., Darzynkiewicz Z. Different patterns of apoptosis of HL-60 cells induced by cycloheximide and camptothecin. J Cell Physiol. 1993 Nov;157(2):263–270. doi: 10.1002/jcp.1041570208. [DOI] [PubMed] [Google Scholar]
  35. Gottlieb J. A., Luce J. K. Treatment of malignant melanoma with camptothecin (NSC-100880). Cancer Chemother Rep. 1972 Feb;56(1):103–105. [PubMed] [Google Scholar]
  36. Gupta E., Lestingi T. M., Mick R., Ramirez J., Vokes E. E., Ratain M. J. Metabolic fate of irinotecan in humans: correlation of glucuronidation with diarrhea. Cancer Res. 1994 Jul 15;54(14):3723–3725. [PubMed] [Google Scholar]
  37. Haas N. B., LaCreta F. P., Walczak J., Hudes G. R., Brennan J. M., Ozols R. F., O'Dwyer P. J. Phase I/pharmacokinetic study of topotecan by 24-hour continuous infusion weekly. Cancer Res. 1994 Mar 1;54(5):1220–1226. [PubMed] [Google Scholar]
  38. Hendricks C. B., Rowinsky E. K., Grochow L. B., Donehower R. C., Kaufmann S. H. Effect of P-glycoprotein expression on the accumulation and cytotoxicity of topotecan (SK&F 104864), a new camptothecin analogue. Cancer Res. 1992 Apr 15;52(8):2268–2278. [PubMed] [Google Scholar]
  39. Hertzberg R. P., Caranfa M. J., Hecht S. M. On the mechanism of topoisomerase I inhibition by camptothecin: evidence for binding to an enzyme-DNA complex. Biochemistry. 1989 May 30;28(11):4629–4638. doi: 10.1021/bi00437a018. [DOI] [PubMed] [Google Scholar]
  40. Hertzberg R. P., Caranfa M. J., Holden K. G., Jakas D. R., Gallagher G., Mattern M. R., Mong S. M., Bartus J. O., Johnson R. K., Kingsbury W. D. Modification of the hydroxy lactone ring of camptothecin: inhibition of mammalian topoisomerase I and biological activity. J Med Chem. 1989 Mar;32(3):715–720. doi: 10.1021/jm00123a038. [DOI] [PubMed] [Google Scholar]
  41. Hochster H., Liebes L., Speyer J., Sorich J., Taubes B., Oratz R., Wernz J., Chachoua A., Raphael B., Vinci R. Z. Phase I trial of low-dose continuous topotecan infusion in patients with cancer: an active and well-tolerated regimen. J Clin Oncol. 1994 Mar;12(3):553–559. doi: 10.1200/JCO.1994.12.3.553. [DOI] [PubMed] [Google Scholar]
  42. Houghton P. J., Cheshire P. J., Hallman J. C., Bissery M. C., Mathieu-Boué A., Houghton J. A. Therapeutic efficacy of the topoisomerase I inhibitor 7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxy-camptothecin against human tumor xenografts: lack of cross-resistance in vivo in tumors with acquired resistance to the topoisomerase I inhibitor 9-dimethylaminomethyl-10-hydroxycamptothecin. Cancer Res. 1993 Jun 15;53(12):2823–2829. [PubMed] [Google Scholar]
  43. Hsiang Y. H., Liu L. F. Identification of mammalian DNA topoisomerase I as an intracellular target of the anticancer drug camptothecin. Cancer Res. 1988 Apr 1;48(7):1722–1726. [PubMed] [Google Scholar]
  44. Hsiang Y. H., Liu L. F., Wall M. E., Wani M. C., Nicholas A. W., Manikumar G., Kirschenbaum S., Silber R., Potmesil M. DNA topoisomerase I-mediated DNA cleavage and cytotoxicity of camptothecin analogues. Cancer Res. 1989 Aug 15;49(16):4385–4389. [PubMed] [Google Scholar]
  45. Jaxel C., Kohn K. W., Wani M. C., Wall M. E., Pommier Y. Structure-activity study of the actions of camptothecin derivatives on mammalian topoisomerase I: evidence for a specific receptor site and a relation to antitumor activity. Cancer Res. 1989 Mar 15;49(6):1465–1469. [PubMed] [Google Scholar]
  46. Kano Y., Suzuki K., Akutsu M., Suda K., Inoue Y., Yoshida M., Sakamoto S., Miura Y. Effects of CPT-11 in combination with other anti-cancer agents in culture. Int J Cancer. 1992 Feb 20;50(4):604–610. doi: 10.1002/ijc.2910500420. [DOI] [PubMed] [Google Scholar]
  47. Kantarjian H. M., Beran M., Ellis A., Zwelling L., O'Brien S., Cazenave L., Koller C., Rios M. B., Plunkett W., Keating M. J. Phase I study of Topotecan, a new topoisomerase I inhibitor, in patients with refractory or relapsed acute leukemia. Blood. 1993 Mar 1;81(5):1146–1151. [PubMed] [Google Scholar]
  48. Kaufmann S. H. Antagonism between camptothecin and topoisomerase II-directed chemotherapeutic agents in a human leukemia cell line. Cancer Res. 1991 Feb 15;51(4):1129–1136. [PubMed] [Google Scholar]
  49. Kawato Y., Aonuma M., Hirota Y., Kuga H., Sato K. Intracellular roles of SN-38, a metabolite of the camptothecin derivative CPT-11, in the antitumor effect of CPT-11. Cancer Res. 1991 Aug 15;51(16):4187–4191. [PubMed] [Google Scholar]
  50. 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(3):192–198. doi: 10.1007/BF00685508. [DOI] [PubMed] [Google Scholar]
  51. Kawato Y., Sekiguchi M., Akahane K., Tsutomi Y., Hirota Y., Kuga H., Suzuki W., Hakusui H., Sato K. Inhibitory activity of camptothecin derivatives against acetylcholinesterase in dogs and their binding activity to acetylcholine receptors in rats. J Pharm Pharmacol. 1993 May;45(5):444–448. doi: 10.1111/j.2042-7158.1993.tb05573.x. [DOI] [PubMed] [Google Scholar]
  52. Kim J. H., Kim S. H., Kolozsvary A., Khil M. S. Potentiation of radiation response in human carcinoma cells in vitro and murine fibrosarcoma in vivo by topotecan, an inhibitor of DNA topoisomerase I. Int J Radiat Oncol Biol Phys. 1992;22(3):515–518. doi: 10.1016/0360-3016(92)90865-f. [DOI] [PubMed] [Google Scholar]
  53. Kim R., Hirabayashi N., Nishiyama M., Jinushi K., Toge T., Okada K. Experimental studies on biochemical modulation targeting topoisomerase I and II in human tumor xenografts in nude mice. Int J Cancer. 1992 Mar 12;50(5):760–766. doi: 10.1002/ijc.2910500516. [DOI] [PubMed] [Google Scholar]
  54. Kunimoto T., Nitta K., Tanaka T., Uehara N., Baba H., Takeuchi M., Yokokura T., Sawada S., Miyasaka T., Mutai M. Antitumor activity of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothec in, a novel water-soluble derivative of camptothecin, against murine tumors. Cancer Res. 1987 Nov 15;47(22):5944–5947. [PubMed] [Google Scholar]
  55. Law T. M., Ilson D. H., Motzer R. J. Phase II trial of topotecan in patients with advanced renal cell carcinoma. Invest New Drugs. 1994;12(2):143–145. doi: 10.1007/BF00874445. [DOI] [PubMed] [Google Scholar]
  56. Lynch T. J., Jr, Kalish L., Strauss G., Elias A., Skarin A., Shulman L. N., Posner M., Frei E., 3rd Phase II study of topotecan in metastatic non-small-cell lung cancer. J Clin Oncol. 1994 Feb;12(2):347–352. doi: 10.1200/JCO.1994.12.2.347. [DOI] [PubMed] [Google Scholar]
  57. Madden K. R., Champoux J. J. Overexpression of human topoisomerase I in baby hamster kidney cells: hypersensitivity of clonal isolates to camptothecin. Cancer Res. 1992 Feb 1;52(3):525–532. [PubMed] [Google Scholar]
  58. Masuda N., Fukuoka M., Kusunoki Y., Matsui K., Takifuji N., Kudoh S., Negoro S., Nishioka M., Nakagawa K., Takada M. CPT-11: a new derivative of camptothecin for the treatment of refractory or relapsed small-cell lung cancer. J Clin Oncol. 1992 Aug;10(8):1225–1229. doi: 10.1200/JCO.1992.10.8.1225. [DOI] [PubMed] [Google Scholar]
  59. Mattern M. R., Hofmann G. A., McCabe F. L., Johnson R. K. Synergistic cell killing by ionizing radiation and topoisomerase I inhibitor topotecan (SK&F 104864). Cancer Res. 1991 Nov 1;51(21):5813–5816. [PubMed] [Google Scholar]
  60. McCabe F. L., Johnson R. K. Comparative activity of oral and parenteral topotecan in murine tumor models: efficacy of oral topotecan. Cancer Invest. 1994;12(3):308–313. doi: 10.3109/07357909409023029. [DOI] [PubMed] [Google Scholar]
  61. Minami H., Beijnen J. H., Verweij J., Ratain M. J. Limited sampling model for area under the concentration time curve of total topotecan. Clin Cancer Res. 1996 Jan;2(1):43–46. [PubMed] [Google Scholar]
  62. Moertel C. G., Schutt A. J., Reitemeier R. J., Hahn R. G. Phase II study of camptothecin (NSC-100880) in the treatment of advanced gastrointestinal cancer. Cancer Chemother Rep. 1972 Feb;56(1):95–101. [PubMed] [Google Scholar]
  63. Muggia F. M., Creaven P. J., Hansen H. H., Cohen M. H., Selawry O. S. Phase I clinical trial of weekly and daily treatment with camptothecin (NSC-100880): correlation with preclinical studies. Cancer Chemother Rep. 1972 Aug;56(4):515–521. [PubMed] [Google Scholar]
  64. Narita M., Nagai E., Hagiwara H., Aburada M., Yokoi T., Kamataki T. Inhibition of beta-glucuronidase by natural glucuronides of kampo medicines using glucuronide of SN-38 (7-ethyl-10-hydroxycamptothecin) as a substrate. Xenobiotica. 1993 Jan;23(1):5–10. doi: 10.3109/00498259309059356. [DOI] [PubMed] [Google Scholar]
  65. Negoro S., Fukuoka M., Masuda N., Takada M., Kusunoki Y., Matsui K., Takifuji N., Kudoh S., Niitani H., Taguchi T. Phase I study of weekly intravenous infusions of CPT-11, a new derivative of camptothecin, in the treatment of advanced non-small-cell lung cancer. J Natl Cancer Inst. 1991 Aug 21;83(16):1164–1168. doi: 10.1093/jnci/83.16.1164. [DOI] [PubMed] [Google Scholar]
  66. Niimi S., Nakagawa K., Sugimoto Y., Nishio K., Fujiwara Y., Yokoyama S., Terashima Y., Saijo N. Mechanism of cross-resistance to a camptothecin analogue (CPT-11) in a human ovarian cancer cell line selected by cisplatin. Cancer Res. 1992 Jan 15;52(2):328–333. [PubMed] [Google Scholar]
  67. O'Connor P. M., Nieves-Neira W., Kerrigan D., Bertrand R., Goldman J., Kohn K. W., Pommier Y. S-phase population analysis does not correlate with the cytotoxicity of camptothecin and 10,11-methylenedioxycamptothecin in human colon carcinoma HT-29 cells. Cancer Commun. 1991 Aug;3(8):233–240. doi: 10.3727/095535491820873083. [DOI] [PubMed] [Google Scholar]
  68. Ohe Y., Sasaki Y., Shinkai T., Eguchi K., Tamura T., Kojima A., Kunikane H., Okamoto H., Karato A., Ohmatsu H. Phase I study and pharmacokinetics of CPT-11 with 5-day continuous infusion. J Natl Cancer Inst. 1992 Jun 17;84(12):972–974. doi: 10.1093/jnci/84.12.972. [DOI] [PubMed] [Google Scholar]
  69. Ohno R., Okada K., Masaoka T., Kuramoto A., Arima T., Yoshida Y., Ariyoshi H., Ichimaru M., Sakai Y., Oguro M. An early phase II study of CPT-11: a new derivative of camptothecin, for the treatment of leukemia and lymphoma. J Clin Oncol. 1990 Nov;8(11):1907–1912. doi: 10.1200/JCO.1990.8.11.1907. [DOI] [PubMed] [Google Scholar]
  70. Ota K., Ohno R., Shirakawa S., Masaoka T., Okada K., Ohashi Y., Taguchi T. [Late phase II clinical study of irinotecan hydrochloride (CPT-11) in the treatment of malignant lymphoma and acute leukemia. The CPT-11 Research Group for Hematological Malignancies]. Gan To Kagaku Ryoho. 1994 Jun;21(7):1047–1055. [PubMed] [Google Scholar]
  71. Pantazis P., Hinz H. R., Mendoza J. T., Kozielski A. J., Williams L. J., Jr, Stehlin J. S., Jr, Giovanella B. C. Complete inhibition of growth followed by death of human malignant melanoma cells in vitro and regression of human melanoma xenografts in immunodeficient mice induced by camptothecins. Cancer Res. 1992 Jul 15;52(14):3980–3987. [PubMed] [Google Scholar]
  72. Pommier Y. DNA topoisomerase I and II in cancer chemotherapy: update and perspectives. Cancer Chemother Pharmacol. 1993;32(2):103–108. doi: 10.1007/BF00685611. [DOI] [PubMed] [Google Scholar]
  73. Potmesil M. Camptothecins: from bench research to hospital wards. Cancer Res. 1994 Mar 15;54(6):1431–1439. [PubMed] [Google Scholar]
  74. Pratt C. B., Stewart C., Santana V. M., Bowman L., Furman W., Ochs J., Marina N., Kuttesch J. F., Heideman R., Sandlund J. T. Phase I study of topotecan for pediatric patients with malignant solid tumors. J Clin Oncol. 1994 Mar;12(3):539–543. doi: 10.1200/JCO.1994.12.3.539. [DOI] [PubMed] [Google Scholar]
  75. Rothenberg M. L., Kuhn J. G., Burris H. A., 3rd, Nelson J., Eckardt J. R., Tristan-Morales M., Hilsenbeck S. G., Weiss G. R., Smith L. S., Rodriguez G. I. Phase I and pharmacokinetic trial of weekly CPT-11. J Clin Oncol. 1993 Nov;11(11):2194–2204. doi: 10.1200/JCO.1993.11.11.2194. [DOI] [PubMed] [Google Scholar]
  76. Rowinsky E. K., Grochow L. B., Ettinger D. S., Sartorius S. E., Lubejko B. G., Chen T. L., Rock M. K., Donehower R. C. Phase I and pharmacological study of the novel topoisomerase I inhibitor 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) administered as a ninety-minute infusion every 3 weeks. Cancer Res. 1994 Jan 15;54(2):427–436. [PubMed] [Google Scholar]
  77. Rowinsky E. K., Grochow L. B., Hendricks C. B., Ettinger D. S., Forastiere A. A., Hurowitz L. A., McGuire W. P., Sartorius S. E., Lubejko B. G., Kaufmann S. H. Phase I and pharmacologic study of topotecan: a novel topoisomerase I inhibitor. J Clin Oncol. 1992 Apr;10(4):647–656. doi: 10.1200/JCO.1992.10.4.647. [DOI] [PubMed] [Google Scholar]
  78. Sakata Y., Shimada Y., Yoshino M., Kambe M., Futatsuki K., Nakao I., Ogawa N., Wakui A., Taguchi T. [A late phase II study of CPT-11, irinotecan hydrochloride, in patients with advanced pancreatic cancer. CPT-11 Study Group on Gastrointestinal Cancer]. Gan To Kagaku Ryoho. 1994 Jun;21(7):1039–1046. [PubMed] [Google Scholar]
  79. Saltz L., Sirott M., Young C., Tong W., Niedzwiecki D., Tzy-Jyun Y., Tao Y., Trochanowski B., Wright P., Barbosa K. Phase I clinical and pharmacology study of topotecan given daily for 5 consecutive days to patients with advanced solid tumors, with attempt at dose intensification using recombinant granulocyte colony-stimulating factor. J Natl Cancer Inst. 1993 Sep 15;85(18):1499–1507. doi: 10.1093/jnci/85.18.1499. [DOI] [PubMed] [Google Scholar]
  80. Shimada Y., Yoshino M., Wakui A., Nakao I., Futatsuki K., Sakata Y., Kambe M., Taguchi T., Ogawa N. Phase II study of CPT-11, a new camptothecin derivative, in metastatic colorectal cancer. CPT-11 Gastrointestinal Cancer Study Group. J Clin Oncol. 1993 May;11(5):909–913. doi: 10.1200/JCO.1993.11.5.909. [DOI] [PubMed] [Google Scholar]
  81. Slichenmyer W. J., Rowinsky E. K., Donehower R. C., Kaufmann S. H. The current status of camptothecin analogues as antitumor agents. J Natl Cancer Inst. 1993 Feb 17;85(4):271–291. doi: 10.1093/jnci/85.4.271. [DOI] [PubMed] [Google Scholar]
  82. Sugimoto Y., Tsukahara S., Oh-hara T., Isoe T., Tsuruo T. Decreased expression of DNA topoisomerase I in camptothecin-resistant tumor cell lines as determined by a monoclonal antibody. Cancer Res. 1990 Nov 1;50(21):6925–6930. [PubMed] [Google Scholar]
  83. Sugimoto Y., Tsukahara S., Oh-hara T., Liu L. F., Tsuruo T. Elevated expression of DNA topoisomerase II in camptothecin-resistant human tumor cell lines. Cancer Res. 1990 Dec 15;50(24):7962–7965. [PubMed] [Google Scholar]
  84. Sugita Y., Negoro T., Matsuda T., Sakamoto T., Tomita M. Improved method for the isolation and preliminary characterization of human DAF (decay-accelerating factor). J Biochem. 1986 Jul;100(1):143–150. doi: 10.1093/oxfordjournals.jbchem.a121686. [DOI] [PubMed] [Google Scholar]
  85. Supko J. G., Malspeis L. Pharmacokinetics of the 9-amino and 10,11-methylenedioxy derivatives of camptothecin in mice. Cancer Res. 1993 Jul 1;53(13):3062–3069. [PubMed] [Google Scholar]
  86. Taguchi T., Tominaga T., Ogawa M., Ishida T., Morimoto K., Ogawa N. [A late phase II study of CPT-11 (irinotecan) in advanced breast cancer. CPT-11 Study Group on Breast Cancer]. Gan To Kagaku Ryoho. 1994 Jun;21(7):1017–1024. [PubMed] [Google Scholar]
  87. Taguchi T., Wakui A., Hasegawa K., Niitani H., Furue H., Ohta K., Hattori T. [Phase I clinical study of CPT-11. Research group of CPT-11]. Gan To Kagaku Ryoho. 1990 Jan;17(1):115–120. [PubMed] [Google Scholar]
  88. Takeuchi S., Dobashi K., Fujimoto S., Tanaka K., Suzuki M., Terashima Y., Hasumi K., Akiya K., Negishi Y., Tamaya T. [A late phase II study of CPT-11 on uterine cervical cancer and ovarian cancer. Research Groups of CPT-11 in Gynecologic Cancers]. Gan To Kagaku Ryoho. 1991 Aug;18(10):1681–1689. [PubMed] [Google Scholar]
  89. Tan K. B., Mattern M. R., Eng W. K., McCabe F. L., Johnson R. K. Nonproductive rearrangement of DNA topoisomerase I and II genes: correlation with resistance to topoisomerase inhibitors. J Natl Cancer Inst. 1989 Nov 15;81(22):1732–1735. doi: 10.1093/jnci/81.22.1732. [DOI] [PubMed] [Google Scholar]
  90. Tanizawa A., Beitrand R., Kohlhagen G., Tabuchi A., Jenkins J., Pommier Y. Cloning of Chinese hamster DNA topoisomerase I cDNA and identification of a single point mutation responsible for camptothecin resistance. J Biol Chem. 1993 Dec 5;268(34):25463–25468. [PubMed] [Google Scholar]
  91. Tanizawa A., Fujimori A., Fujimori Y., Pommier Y. Comparison of topoisomerase I inhibition, DNA damage, and cytotoxicity of camptothecin derivatives presently in clinical trials. J Natl Cancer Inst. 1994 Jun 1;86(11):836–842. doi: 10.1093/jnci/86.11.836. [DOI] [PubMed] [Google Scholar]
  92. Tsuruo T., Matsuzaki T., Matsushita M., Saito H., Yokokura T. Antitumor effect of CPT-11, a new derivative of camptothecin, against pleiotropic drug-resistant tumors in vitro and in vivo. Cancer Chemother Pharmacol. 1988;21(1):71–74. doi: 10.1007/BF00262744. [DOI] [PubMed] [Google Scholar]
  93. Verweij J., Lund B., Beijnen J., Planting A., de Boer-Dennert M., Koier I., Rosing H., Hansen H. Phase I and pharmacokinetics study of topotecan, a new topoisomerase I inhibitor. Ann Oncol. 1993 Sep;4(8):673–678. doi: 10.1093/oxfordjournals.annonc.a058623. [DOI] [PubMed] [Google Scholar]
  94. Wall J. G., Burris H. A., 3rd, Von Hoff D. D., Rodriguez G., Kneuper-Hall R., Shaffer D., O'Rourke T., Brown T., Weiss G., Clark G. A phase I clinical and pharmacokinetic study of the topoisomerase I inhibitor topotecan (SK&F 104864) given as an intravenous bolus every 21 days. Anticancer Drugs. 1992 Aug;3(4):337–345. doi: 10.1097/00001813-199208000-00004. [DOI] [PubMed] [Google Scholar]
  95. Wall M. E., Wani M. C., Nicholas A. W., Manikumar G., Tele C., Moore L., Truesdale A., Leitner P., Besterman J. M. Plant antitumor agents. 30. Synthesis and structure activity of novel camptothecin analogs. J Med Chem. 1993 Sep 3;36(18):2689–2700. doi: 10.1021/jm00070a013. [DOI] [PubMed] [Google Scholar]
  96. Walton M. I., Whysong D., O'Connor P. M., Hockenbery D., Korsmeyer S. J., Kohn K. W. Constitutive expression of human Bcl-2 modulates nitrogen mustard and camptothecin induced apoptosis. Cancer Res. 1993 Apr 15;53(8):1853–1861. [PubMed] [Google Scholar]
  97. Wani M. C., Nicholas A. W., Manikumar G., Wall M. E. Plant antitumor agents. 25. Total synthesis and antileukemic activity of ring A substituted camptothecin analogues. Structure-activity correlations. J Med Chem. 1987 Oct;30(10):1774–1779. doi: 10.1021/jm00393a016. [DOI] [PubMed] [Google Scholar]
  98. Wani M. C., Ronman P. E., Lindley J. T., Wall M. E. Plant antitumor agents. 18. Synthesis and biological activity of camptothecin analogues. J Med Chem. 1980 May;23(5):554–560. doi: 10.1021/jm00179a016. [DOI] [PubMed] [Google Scholar]
  99. Woessner R. D., Eng W. K., Hofmann G. A., Rieman D. J., McCabe F. L., Hertzberg R. P., Mattern M. R., Tan K. B., Johnson R. K. Camptothecin hyper-resistant P388 cells: drug-dependent reduction in topoisomerase I content. Oncol Res. 1992;4(11-12):481–488. [PubMed] [Google Scholar]
  100. Zhang H., D'Arpa P., Liu L. F. A model for tumor cell killing by topoisomerase poisons. Cancer Cells. 1990 Jan;2(1):23–27. [PubMed] [Google Scholar]
  101. de Forni M., Bugat R., Chabot G. G., Culine S., Extra J. M., Gouyette A., Madelaine I., Marty M. E., Mathieu-Boué A. Phase I and pharmacokinetic study of the camptothecin derivative irinotecan, administered on a weekly schedule in cancer patients. Cancer Res. 1994 Aug 15;54(16):4347–4354. [PubMed] [Google Scholar]
  102. de Forni M., Bugat R., Chabot G. G., Culine S., Extra J. M., Gouyette A., Madelaine I., Marty M. E., Mathieu-Boué A. Phase I and pharmacokinetic study of the camptothecin derivative irinotecan, administered on a weekly schedule in cancer patients. Cancer Res. 1994 Aug 15;54(16):4347–4354. [PubMed] [Google Scholar]
  103. van der Zee A. G., Hollema H., de Jong S., Boonstra H., Gouw A., Willemse P. H., Zijlstra J. G., de Vries E. G. P-glycoprotein expression and DNA topoisomerase I and II activity in benign tumors of the ovary and in malignant tumors of the ovary, before and after platinum/cyclophosphamide chemotherapy. Cancer Res. 1991 Nov 1;51(21):5915–5920. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES