Topotecan (HYCAMTIN®; GlaxoSmithKline, Brentford, Middlesex, UK) is a novel topoisomerase I inhibitor with potentially broad applicability in the treatment of solid and hematologic malignancies. In addition to its use in relapsed small-cell lung cancer (SCLC), topotecan is under investigation in numerous studies for first-line therapy in SCLC and for first- and second-line treatment of non-small-cell lung cancer (NSCLC). Preliminary evidence presented in this supplement demonstrates that single-agent topotecan and topotecan-based combination regimens are active in these settings. In addition to its potential use in SCLC and NSCLC, the feasibility and antitumor activity of topotecan as single-agent therapy and in combination therapy are under active investigation in a variety of other solid and hematologic tumors. Other important avenues of investigation include the feasibility and tumor activity of a more convenient oral formulation, as well as the investigation of alternate regimens (e.g., 3-day, weekly), with high priority given to regimen toxicity, patient convenience, and quality of life. Preliminary results of some of these trials are presented in this summary. The results of other clinical experience trials are eagerly anticipated.

Liebes L, Potmesil M, Kim T, Pease D, Buckley M, Fry D, Cho J, Adler H, Dar K, Zeleniuch-Jacquotte A, Hochster H: Pharmacodynamics of topoisomerase I inhibition: Western blot determination of topoisomerase I and cleavable complex in patients with upper gastrointestinal malignancies treated with topotecan. Clin Cancer Res 1998;4:545–557.
Cersosimo RJ: Topotecan: a new topoisomerase I inhibiting antineoplastic agent. Ann Pharmacother 1998;32:1334–1343.
Kollmannsberger C, Mross K, Jakob A, Kanz L, Bokemeyer C: Topotecan – A novel topoisomerase I inhibitor: pharmacology and clinical experience. Oncology 1999;56:1–12.
Ormrod D, Spencer CM: Topotecan: a review of its efficacy in small cell lung cancer. Drugs 1999;58:533–551.
Evans WK, Feld R, Murray N, Willan A, Coy P, Osoba D, Shepherd FA, Clark DA, Levitt M, MacDonald A: Superiority of alternating non-cross-resistant chemotherapy in extensive small cell lung cancer. A multicenter, randomized clinical trial by the National Cancer Institute of Canada. Ann Intern Med 1987;107:451–458.
Fukuoka M, Takada M, Negoro S, Kusunoki Y, Matsui K, Ryu S, Sakai N, Takifuji N, Kudoh S, Tamai S: Alternating non-cross resistant chemotherapy for small cell lung cancer. Jpn J Clin Oncol 1986;16:261–270.
Havemann K, Wolf M, Holle R, Gropp C, Drings P, Manke HG, Hans K, Schroeder M, Heim M, Victor N: Alternating versus sequential chemotherapy in small cell lung cancer. A randomized German multicenter trial. Cancer 1987;59:1072–1082.
von Pawel J, Gatzemeier U, Pujol JL, Moreau L, Bildat S, Ranson M, Richardson G, Steppert C, Riviere A, Camlett I, Lane S, Ross G: Phase II comparator study of oral versus intravenous topotecan in patients with chemosensitive small-cell lung cancer. J Clin Oncol 2001;19:1743–1749.
Eckardt JR, Fanucchi MP, Stewart DJ, Beckman RA, Dobbs TW, Wilson JJ, Ho ML, Fields SZ: A phase I/II study using oral topotecan (OT) with intravenous paclitaxel (P) as first-line therapy for patients (pts) with advanced non-small cell lung cancer (NSCLC) [abstract]. Lung Cancer 2000;29(suppl 1):6 (abstract 13).
Eckardt JR, Palmer MC, Fanucchi MP, Gralla R, Martins H, Poulin R, Fields SZ: Single agent oral topotecan (OT) as first-line treatment for patients (pts) with extensive disease (ED) small cell lung cancer (SCLC) ineligible for standard therapy: A phase II study [abstract]. Lung Cancer 2000;29(suppl 1):10 (abstract 25).
Schiller JH, Kim K, Hutson P, DeVore R, Glick J, Stewart J, Johnson D: Phase II study of topotecan in patients with extensive-stage small-cell carcinoma of the lung: an Eastern Cooperative Oncology Group Trial. J Clin Oncol 1996;14:2345–2352.
Ardizzoni A, Hansen H, Dombernowsky P, Gamucci T, Kaplan S, Postmus P, Giaccone G, Schaefer B, Wanders J, Verweij J: Topotecan, a new active drug in the second-line treatment of small-cell lung cancer: a phase II study in patients with refractory and sensitive disease. The European Organization for Research and Treatment of Cancer Early Clinical Studies Group and New Drug Development Office, and the Lung Cancer Cooperative Group. J Clin Oncol 1997;15:2090–2096.
Eckardt J, Gralla R, Palmer MC, Gandara D, Laplante J, Sandler A, Fields SZ, Fitts D, Broom C: Topotecan (T) as second-line therapy in patients (Pts) with small cell lung cancer (SCLC): a phase II study [abstract]. Ann Oncol 1996;7(suppl 5):107 (abstract 513P).
Eckardt J, Depierre A, Ardizzoni A, Von Pawel J, Fields S: Pooled analysis of topotecan (T) in the second-line treatment of patients (pts) with sensitive small cell lung cancer (SCLC) [abstract]. Proc Am Soc Clin Oncol 1997;16:452a (abstract 1624).
Gervais R: The Topotecan SCLC Study Group: Topotecan/cisplatin versus topotecan/etoposide in untreated small cell lung cancer (SCLC) extensive disease: a randomized phase II study. Presented at: World Congress of Lung Cancer. Sponsored by the International Association for the Study of Lung Cancer and the Japan Lung Cancer Society; September, 2000: Tokyo, Japan.
Clark P, Sutton P, Smith D, Graham R: A phase I/II study of a 5-day schedule of intravenous topotecan (T) and etoposide (E) regimen in untreated small cell lung cancer (SCLC). A promising combination with potential for oral delivery [abstract]. Lung Cancer 2000;29(suppl 1):40 (abstract 128).
Jett JR, Hatfield A, Bauman M, Hillman S, Soori G, Veeder M, Morton R: Phase II trial of topotecan and paclitaxel (TP) with G-CSF support alternating with etoposide and cisplatin (EC) in previously untreated extensive stage small cell lung cancer (ED-SCLC): a North Central Cancer Treatment Group study [abstract]. Lung Cancer 2000;29(suppl 1):52 (abstract 168).
Hainsworth JD, Gray JR, Burris HA, Greco FA: Paclitaxel, carboplatin and topotecan as initial therapy for small cell lung cancer [abstract]. Lung Cancer 2000;29(suppl 1):40 (abstract 127).
Gillenwater HH, McCune JS, Donahue AE, Faucette SR, Shifflett S, Lindley C, Socinski MA: Phase I trial of topotecan (T), carboplatin (C) and etoposide (E) for extensive stage small cell lung cancer (ES-SCLC) [abstract]. Lung Cancer 2000;29(suppl 1):51 (abstract 164).
Ventriglia M, Cabrera L, Maidana M, Vigo S, Cilurzo M, Estévez R: A phase II trial of topotecan (Hycamtin®) with ifosfamide (Duvaxan®) plus mesna (Mesnex®) as first line treatment in patients (pts) with small cell lung cancer (SCLC). A preliminary report [abstract]. Lung Cancer 2000;29(suppl 1):67 (abstract 218).
Perez-Soler R, Fossella FV, Glisson BS, Lee JS, Murphy WK, Shin DM, Kemp BL, Lee JJ, Kane J, Robinson RA, Lippman SM, Kurie JM, Huber MH, Raber MN, Hong WK: Phase II study of topotecan in patients with advanced non-small-cell lung cancer previously untreated with chemotherapy. J Clin Oncol 1996;14:503–513.
Palshof T, Rivière A, Moreau L, Breton JL, Hearn S, Fields SZ, Ross G: Phase II study of oral topotecan (T) with cisplatin (C) in advanced, non-resectable NSCLC. A promising combination [abstract]. Lung Cancer 2000;29(suppl 1):36 (abstract 115).
Pujol JL, von Pawel J, Tumolo S, Martoni A, Hearn S, Fields SZ, Ross G: Phase II study of topotecan (T) IV with carboplatin (Carbo) in advanced NSCLC [abstract]. Lung Cancer 2000;29(suppl 1):86 (abstract 285).
Stupp R, Bauer J, Perey L, Ketterer N, Fucina N, Perrier R, Leyvraz S: Topotecan and vinorelbine is as effective, but less toxic than platinum-containing regimens against NSCLC. Promising results of this outpatient regimen in a phase I/II trial [abstract]. Lung Cancer 2000;29(suppl 1):36 (abstract 114).
Hardman WE, Moyer MP, Cameron IL: Efficacy of treatment of colon, lung and breast human carcinoma xenografts with: doxorubicin, cisplatin, irinotecan or topotecan. Anticancer Res 1999;19:2269–2274.
Gerrits CJ, Burris H, Schellens JH, Planting AS, van den Burg ME, Rodriguez GI, van Beurden V, Loos WJ, Hudson I, Fields S, Verweij J, von Hoff DD: Five days of oral topotecan (Hycamtin), a phase I and pharmacological study in adult patients with solid tumours. Eur J Cancer 1998;34:1030–1035.
Beran M, Kantarjian H: Topotecan in the treatment of hematologic malignancies. Semin Hematol 1998;35:26–31.
Park SJ, Kim DW, Kim HJ, Eom HS, Min CK, Lee JW, Min WS, Kim CC: Topotecan-based combination chemotherapy in patients with transformed chronic myelogenous leukemia and advanced myelodysplastic syndrome. Korean J Intern Med 2000;15:122–126.
Estey EH: Incorporating new modalities into guidelines. Topotecan for myelodysplastic syndromes. Oncology (Huntingt) 1998;12:81–86.
Cortes J, Estey E, Beran M, O’Brien S, Giles F, Koller C, Keating M, Kantarjian H: Cyclophosphamide, ara-C and topotecan (CAT) for patients with refractory or relapsed acute leukemia. Leuk Lymphoma 2000;36:479–484.
Kantarjian H: New developments in the treatment of acute myeloid leukemia: focus on topotecan. Semin Hematol 1999;36:16–25.
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