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A Phase II Trial of 9-Aminocaptothecin (9-AC) as a 120-h Infusion in Patients with Non-Small Cell Lung Cancer

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Abstract

In a previous phase II trial of thesynthetic topoisomerase I inhibitor,9-aminocamptothecin (9-AC), given as a72-h infusion, we identified modestsingle agent activity of 9% in patientswith previously untreated advancednon-small cell lung cancer (NSCLC).Preclinical studies suggested that a moreprolonged continuous infusion of the drugmight lead to greater antitumor activity. Aphase I study recommended a phase II doseof 25 μg/m2/hr for 120 h(3000 μg/m2 over 5 days),administered for 2 consecutive weeks of a3-week cycle. We utilized this schedule andenrolled 13 chemotherapy-naıve patientswith Stage IIIB and IV NSCLC in this trial:median age 67 (range 57–74); 46% male;92% stage IV; and median performancestatus 1. Twelve patients are availablefor response and toxicity evaluation after2 cycles of therapy. One patient achieveda partial response. Four patients hadstable disease while seven patients hadprogressive disease. Patients with stableor progressive disease after two cyclesreceived no additional 9-AC, and wereoffered conventional chemotherapy. Themedian survival time was 10.2 months andthe one-year survival rate 28% (95%confidence interval, 5–58%). Significant toxicities includedmyelosuppression, fatigue, and anorexia. One patient had grade 4 neutropeniafollowing the first week of cycle 2, anddid not receive additional therapy. Therewere no neutropenia-related infections.These data suggest that this prolongedschedule is unlikely to increase 9-AC'svery modest activity in NSCLC above thatseen with the simpler 72-hadministration schedule. Furtherevaluation of 9-AC in NSCLC is notrecommended.

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Authors and Affiliations

  1. Section of Hematology/Oncology, Department of Medicine and Cancer Research Center, University of Chicago, Chicago, IL, U.S.A.

    Everett E. Vokes, Gary S. Gordon, Charles M. Rudin, Ann M. Mauer, Sylvia Watson, Stuart Krauss, Rose Arrieta, Harvey M. Golomb & Philip C. Hoffman

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  1. Everett E. Vokes
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  2. Gary S. Gordon
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  3. Charles M. Rudin
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Vokes, E.E., Gordon, G.S., Rudin, C.M. et al. A Phase II Trial of 9-Aminocaptothecin (9-AC) as a 120-h Infusion in Patients with Non-Small Cell Lung Cancer. Invest New Drugs 19, 329–333 (2001). https://doi.org/10.1023/A:1010674113243

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