The single-agent activity of intravenous (i.v.) topotecan has been established in small-cell lung cancer (SCLC), with overall tumor responses of 39% in previously untreated patients and 11–37% in relapsed patients. An oral formulation of topotecan has been developed that is more convenient for patients, which may lead to greater compliance and greater prescribing flexibility for use in combination with other active agents. We initiated a phase II trial to test the feasibility of oral topotecan administered at 2.0 mg/m2 on days 1–5 of a 21-day cycle in previously untreated SCLC patients. Patients received a median of 5 courses of oral topotecan. Grade 3/4 myelosuppression was common in patients treated with 2.0 mg/m2; secondary to 2 patients developing fatal sepsis, patients enrolled later in the study were treated at 1.7 mg/m2. At both doses, the majority of nonhematologic toxicity was grade 1/2 in severity, and there were no discontinuations attributed to nonhematologic toxicity. In a patient population reflective of the general SCLC population (i.e. elderly with multiple comorbidities), oral topotecan was generally well tolerated at the lower dose level, with a preliminary antitumor activity profile comparable to i.v. topotecan. Clinical studies are currently under way to compare the antitumor activity of oral topotecan with i.v. topotecan in second-line SCLC and investigate oral topotecan in combination with other active agents in SCLC.

Roth BJ, Johnson DH, Einhorn LH, Schacter LP, Cherng NC, Cohen HJ, Crawford J, Randolph JA, Goodlow JL, Broun GO: Randomized study of cyclophosphamide, doxorubicin, and vincristine versus etoposide and cisplatin versus alternation of these two regimens in extensive small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group. J Clin Oncol 1992;10:282–291.
Pujol JL, Daures JP, Riviere A, Quoix E, Westeel V, Quantin X, Breton JL, Lemarie E, Poudenx M, Milleron B, Moro D, Debieuvre D, Le Chevalier T: Etoposide plus cisplatin with or without the combination of 4′-epidoxorubicin plus cyclophosphamide in treatment of extensive small-cell lung cancer: a French Federation of Cancer Institutes multicenter phase III randomized study. J Natl Cancer Inst 2001;93:300–308.
Urban T, Chastang C, Lebas FX, Duhamel JP, Adam G, Darse J, Brechot JM, Lebeau B: The addition of cisplatin to cyclophosphamide-doxorubicin-etoposide combination chemotherapy in the treatment of patients with small cell lung carcinoma: a randomized study of 457 patients. ‘Petites Cellules’ Group. Cancer 1999;86:2238–2245.
von Pawel J, Schiller JH, Shepherd FA, Fields SZ, Kleisbauer JP, Chrysson NG, Stewart DJ, Clark PI, Palmer MC, Depierre A, Carmichael J, Krebs JB, Ross G, Lane SR, Gralla R: Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol 1999;17:658–667.
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.
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).
Gridelli C: Topotecan, a recent discovery and prospects for treating tumors of the lung. Tumori 1999;85(suppl 1):16–22.
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.
Schellens JH, Creemers GJ, Beijnen JH, Rosing H, de Boer-Dennert M, McDonald M, Davies B, Verweij J: Bioavailability and pharmacokinetics of oral topotecan: a new topoisomerase I inhibitor. Br J Cancer 1996;73:1268–1271.
Kuhn J, Rizzo J, Eckardt J, Fields S, Cobb P, Rodriquez G, Rinadi D, Drengler R, Smith L, Peacock N, Thurman A, DeLaCruz P, Hodges S, Von Hoff D, Burris H: Phase I bioavailability study of oral topotecan. Proc Am Soc Clin Oncol 1995;14:474 (abstract 1538).
Burris HA 3rd: The evolving role of oral topotecan. Semin Hematol 1999;36:26–32.
Hutchins LF, Unger JM, Crowley JJ, Coltman CA Jr, Albain KS: Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 1999;341:2061–2067.
Houghton PJ, Cheshire PJ, Hallman JD II, Lutz L, Friedman HS, Danks MK, Houghton JA: Efficacy of topoisomerase I inhibitors, topotecan and irinotecan, administered at low dose levels in protracted schedules to mice bearing xenografts of human tumors. Cancer Chemother Pharmacol 1995;36:393–403.
Burris HA III, Hanauske AR, Johnson RK, Marshall MH, Kuhn JG, Hilsenbeck SG, Von Hoff DD: Activity of topotecan, a new topoisomerase I inhibitor, against human tumor colony-forming units in vitro. J Natl Cancer Inst 1992;84:1816–1820.
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