Summary
Purpose: To evaluate the efficacy and safety of amrubicin, (+)-(7S, 9S)-9-acetyl-9-amino-7-[(2-deoxy-β-D-erythro-pentopyranosyl )oxy ]-7,8,9,10-tetrahydro-6,11-dihydroxy-5,12-naphthacenedione hydrochloride, in previously untreated patients with extensive-disease small cell lung cancer (SCLC).
Patients and methods: A total of 35 previously untreated patients with extensive-disease SCLC were entered into the study. Amrubicin was given by daily intravenous infusion at 45 mg/m2/day for 3 consecutive days, every 3 weeks. Unless there was tumor regression of 25% or greater after the first cycle, or 50% or greater after the second cycle, treatment was switched to salvage chemotherapy in combination with etoposide (100 mg/m2, days 1, 2, and 3) and cisplatin (80 mg/m2, day 1).
Results: Of the 35 patients entered, 33 were eligible and assessable for efficacy and toxicity. Of the 33 patients, 3 (9.1%) had a complete response (95% confidence interval [CI], 1.9–24.3%) and 22 had a partial response, for an overall response rate of 75.8% (95% CI, 57.7–88.9%). Median survival time was 11.7 months (95% CI, 9.9–15.3 months), and 1-year and 2-year survival rates were 48.5% and 20.2%, respectively. The most common toxicity was hematologic. Non-hematologic toxicity of grade 3 or 4 was only seen in 3 patients with anorexia (9.1%) and 1 patient with alopecia (3.0%). Salvage chemotherapy was administered to only 6 patients.
Conclusion: Amrubicin was active for extensive-disease SCLC with acceptable toxicity. Further studies in combination with other agents for SCLC are warranted.
Similar content being viewed by others
References
Murren J, Glatstein E, Pass H (2001) Small cell lung cancer. In: DeVita VTJ, Hellman S, Rosenberg SA (eds) Cancer: principles and practice of oncology, 6th edn. Lippincott Williams and Wilkins, Philadelphia, pp 983–1018
Aisner J (1996) Extensive-disease small-cell lung cancer: the thrill of victory; the agony of defeat. J Clin Oncol 14:658–665
Noda K, Nishiwaki Y, Kawahara M, Negoro S, Sugiura T, Yokoyama A, Fukuoka M, Mori K, Watanabe K, Tamura T, Yamamoto S, Saijo N, for the Japan Clinical Oncology Group (2002) Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med 346:85–91
Aisner J, Alberto P, Bitran J, Comis R, Daniels J, Hansen H, Ikegami H, Smyth J (1983) Role of chemotherapy in small cell lung cancer: a consensus report of the International Association for the Study of Lung Cancer workshop. Cancer Treat Rep 67:37–43
Ishizumi K, Ohashi N, Tanno N (1987) Stereospecific total synthesis of 9-aminoanthracyclines: (+)-9-amino-9-deoxydaunomycin and related compounds. J Org Chem 52:4477–4485
Morisada S, Yanagi Y, Noguchi T, Kashiwazaki Y, Fukui M (1989) Antitumor activities of a novel 9-aminoanthracycline (SM-5887) against mouse experimental tumors and human tumor xenografts. Jpn J Cancer Res 80:69–76
Morisada S, Yanagi Y, Kashiwazaki Y, Fukui M (1989) Toxicological aspects of a novel 9-aminoanthracycline, SM-5887. Jpn J Cancer Res 80:77–82
Suzuki T, Minamide S, Iwasaki T, Yamamoto H, Kanda H (1997) Cardiotoxicity of a new anthracycline derivative (SM-5887) following intravenous administration to rabbits: comparative study with doxorubicin. Invest New Drugs 15:219–225
Noda T, Watanabe T, Kohda A, Hosokawa S, Suzuki T (1998) Chronic effects of a novel synthetic anthracycline derivative (SM-5887) on normal heart and doxorubicin-induced cardiomyopathy in beagle dogs. Invest New Drugs 16:121–128
Yamaoka T, Hanada M, Ichii S, Morisada S, Noguchi T, Yanagi Y (1998) Cytotoxicity of amrubicin, a novel 9-aminoanthracycline, and its active metabolite amrubicinol on human tumor cells. Jpn J Cancer Res 89:1067–1073
Noguchi T, Ichii S, Morisada S, Yamaoka T, Yanagi Y (1998) In vivo efficacy and tumor-selective metabolism of amrubicin to its active metabolite. Jpn J Cancer Res 89:1055–1060
Hanada M, Mizuno S, Fukushima A, Saito Y, Noguchi T, Yamaoka T (1998) A new antitumor agent amrubicin induces cell growth inhibition by stabilizing topoisomerase II-DNA complex. Jpn J Cancer Res 89:1229–1238
Negoro S, Fukuoka M, Nakamura S, Ikegami H, Sugiura T, Ariyoshi Y, Takada M, Yana T, Ogawa M (1995) Phase I–II study of amrubicin (SM-5887), a novel 9-aminoanthracycline, by iv administration for 3 consecutive days in patients with advanced non-small-cell lung cancer (abstract). Proc Am Soc Clin Oncol 14:361
Japan Society for Cancer Therapy (1993) Criteria for the evaluation of the clinical effects of solid cancer chemotherapy. J Jpn Soc Cancer Ther 28:101–130
World Health Organization (1979) Handbook for reporting results of cancer treatment (WHO Offst Publication No. 48). World Health Organization, Geneva, Switzerland
Kaplan WH, Meier P (1952) Nonparametric estimation from incomplete observations. J Am Atat Assoc 53:583–612
Grant SC, Gralla RJ, Kris MG, Orazem J, Kitsis EA (1992) Single-agent chemotherapy trials in small-cell lung cancer, 1970 to 1990: the case for studies in previously treated patients. J Clin Oncol 10:484–498
Negoro S, Fukuoka M, Niitani H, Suzuki A, Nakabayashi T, Kimura M, Motomiya M, Kurita Y, Hasegawa K, Kuriyama T, Nishiwaki Y, Ogawa M, Nakao I, Saijo N, Obo K, Furue H, Ariyoshi Y, Shimokata K, Furuse K, Nakajima S, Irie K, Kimura I, Ogura T, Fujii M, Hara N, Hara Y, Nakano N, Araki J, Miyata Y, Taguchi T (1991) A phase II study of CPT-11, a camptothecin derivative, in patients with primary lung cancer. CPT-11 Cooperative Study Group. Jpn J Cancer Chemother 18:1013–1019
Masuda N, Fukuoka M, Kusunoki Y, Matsui K, Takifuji N, Kudoh S, Negoro S, Nishioka M, Nakagawa K, Takada M (1992) CPT-11: a new derivative of camptothecin for the treatment of refractory or relapsed small-cell lung cancer. J Clin Oncol 10:1225–1229
Schiller JH, Kim K, Hutson P, DeVore R, Glick J, Stewart J, Johnson D (1996) 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 14:2345–2352
Ettinger DS, Finkelstein DM, Sarma RP, Johnson DH (1995) Phase II study of paclitaxel in patients with extensive-disease small-cell lung cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol 13:1430–1435
Kirschling R, Jung S, Jett J (1994) A phase II study of taxol and GCSF in previously untreated patients with extensive stage small cell lung cancer (SCLC) (abstract). Proc Am Soc Clin Oncol 13:326
Hesketh P, Crowley J, Burris HA 3rd, Williamson SK, Balcerzak SP, Peereboom D, Goodwin JW, Gross HM, Moore DF Jr, Livingston RB, Gandara DR (1999) Evaluation of docetaxel in previously untreated extensive-stage small cell lung cancer: a Southwest Oncology Group phase II trial. Cancer J Sci Am 5:237–241
Cormier Y, Eisenhauer E, Muldal A, Gregg R, Ayoub J, Goss G, Stewart D, Tarasoff P, Wong D (1994) Gemcitabine is an active new agent in previously untreated extensive small cell lung cancer (SCLC). A study of the National Cancer Institute of Canada Clinical Trials Group. Ann Oncol 5:283–285
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yana, T., Negoro, S., Takada, M. et al. Phase II study of amrubicin in previously untreated patients with extensive-disease small cell lung cancer: West Japan Thoracic Oncology Group (WJTOG) study. Invest New Drugs 25, 253–258 (2007). https://doi.org/10.1007/s10637-006-9012-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10637-006-9012-9