Abstract
9-Aminocamptothecin (9-AC) is a water-insoluble camptothecin derivative that demonstrated broad activity in pre-clinical studies. In vitro, greater anti-tumor efficacy can be achieved with prolonged administration. A minor response was observed in gastric cancer in a phase I study. We conducted a phase II study of 9-AC in 15 patients with previously untreated metastatic gastric cancer and adenocarcinoma of the gastroesophageal junction. 9-AC was administered at a dose of 25 μg/m2/h over 120 hours (3000 μg/m2 over 5 days) on two consecutive weeks every 21 days. Fourteen patients were evaluable for response. There were no objective responses. Three patients had stable disease lasting a median of 3.4 months (range 1.6–4.3 months). Median time to progression was 1.4 months; median survival was 5.2 months. Grade 3 neutropenia developed in 20% of patients, and anemia in 7%. Grade 3 nausea and fatigue each developed in 7% of patients. We conclude that 9-AC given by 120-hour continuous infusion demonstrates no clinical activity in patients with metastatic gastric cancer.
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Jemal A, Murray T, Samuels A et al.: Cancer statistics, 2003. CA Cancer J Clin 53: 5–26, 2003
Dragovich T, Kindler HL: Nonsurgical Palliative Therapy of Advanced Gastric Cancer. In: Posner MC, Vokes EE, Weichselbaum R (eds) American Cancer Society Atlas of Clinical Oncology Series: Cancer of the Upper Gastrointestinal Tract. BC Decker, Inc, Hamilton, Ontario, 2002, pp 290–307
Vanhoefer U, Rougier P, Wilke H, Ducreux MP, Lacave AJ, Van Cutsem E, Planker M, Santos JG, Piedbois P, Paillot B, Bodenstein H, Schmoll HJ, Bleiberg H, Nordlinger B, Couvreur ML, Baron B, Wils JA: Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: A trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer. J Clin Oncol 18: 2648–2657, 2000
Takimoto C, Thomas R: The clinical development of 9-Aminocamptothecin. Ann NY Acad Sci 922: 224–236, 2000
Thomas RR, Dahut W, Harold N, Grem JL, Monahan BP, Liang M, Band RA, Cottrell J, Llorens V, Smith JA, Corse W, Arbuck SG, Wright J, Chen AP, Shapiro JD, Hamilton JM, Allegra CJ, Takimoto CH: A phase I and pharmacologic study of 9-aminocamptothecin administered as a 120-h infusion weekly to adult cancer patients. Cancer Chemother Pharmacol 48: 215–222, 2001
Rubin E, Wood V, Bharti A, Trites D, Lynch C, Hurwitz S, Bartel S, Levy S, Rosowsky A, Toppmeyer D: A phase I and pharmacokinetic study of a new camptothecin derivative, 9-aminocamptothecin. Clin Cancer Res 1: 269–276, 1995
Simon R: Optimal two-stage designs for phase II clinical trials. Controlled Clinical Trials 10: 1–10, 1989
Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53: 457–481, 1958
Pazdur R, Medgyesy DC, Winn RJ, Dakhil SR, Moore DF, Scalzo A, Hoff PM, Arbuck SG, Abbruzzesse JL: Phase II trial of 9-aminocamptothecin (NSC 603071) administered as a 120-hour continuous infusion weekly for three weeks in metastatic colorectal carcinoma. Invest New Drugs 16: 341–346, 1999
Pazdur R, Diaz-Canton E, Ballard WP, Bradof JE, Graham S, Arbuck SG, Abbruzzese JL, Winn R: Phase II trial of 9-aminocamptothecin administered as a 72-hour continuous infusion in metastatic colorectal carcinoma. J Clin Oncol 15: 2905–2909, 1997
Vokes EE, Gordon GS, Rudin CM, Mauer AM, Watson S, Krauss S, Arrieta R, Golomb H, Hoffman PC: A phase II trial of 9-aminocamptothecin (9-AC) as a 120-h infusion in patients with non-small cell lung cancer. Invest New Drugs 19: 329–333, 2001
Vokes EE, Ansari RH, Masters GA, Hoffman PC, Klepsch A, Ratain MJ, Sciortino DF, Lad TE, Krauss S, Fishkin PAS, Golomb HM: A phase II study of 9-aminocamptothecin in advanced non-small cell lung cancer. Annals of Oncology 9: 1085–1090, 1998
Lad T, Rosen F, Sciortino D, Brockstein B, Keubler JP, Arietta R, Vokes EE: Phase II trial of aminocamptothecin (9-AC/DMA) in patients with advanced squamous cell head and neck cancer. Invest New Drugs 18: 261–263, 2000
McCarthy N, Sarosy G, Minasian L, Davis P, Tomkins A, Dyer V, Jones-Wells A, Smith J, Kohler D, Takimoto C, Figg WD, Kohn EC, Reed E: Phase II and pharmacokinetic (PK) study of 9-aminocamptothecin (9AC) in recurrent epithelial ovarian cancer. Proc Am Soc Clin Oncol 18: 363a, 1999
Speyer J, Hochster H, Mandeli J, Krook J, Runowicz, Wadler S: Phase II study of 72 hr 9-amino-camptothecin (9AC) infusion in second-line therapy of ovarian cancer (a NYGOG and ECOG study). Proc Am Soc Clin Oncol 18: 363a, 1999
Saltz LB, Schwartz GK, Ilson DH, Quan V, Kelsen DP: A phase II study of topotecan administered five times daily in patients with advanced gastric cancer. Am J Clin Oncol 20: 621–625, 1997
Bleiberg H: CPT-11 in gastrointestinal cancer. Eur J Cancer 35: 371–379, 1999
Boku N, Ohtsu A, Shimada Y, Shirao K, Seki S, Saito H, Sakata Y, Hyodo I: Phase II study of a combination of irinotecan and cisplatin against metastatic gastric cancer. J Clin Oncol 17: 319–323, 1999
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Kindler, H.L., Avadhani, A., Wade-Oliver, K. et al. 9-Aminocamptothecin (9-AC) given as a 120-hour continuous infusion in patients with advanced adenocarcinomas of the stomach and gastroesophageal junction: A phase II trial of the University of Chicago phase II consortium. Invest New Drugs 22, 323–327 (2004). https://doi.org/10.1023/B:DRUG.0000026259.28395.c2
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DOI: https://doi.org/10.1023/B:DRUG.0000026259.28395.c2