Investigational New Drugs

, Volume 25, Issue 3, pp 253–258 | Cite as

Phase II study of amrubicin in previously untreated patients with extensive-disease small cell lung cancer: West Japan Thoracic Oncology Group (WJTOG) study

  • Takashi YanaEmail author
  • Shunichi Negoro
  • Minoru Takada
  • Soichiro Yokota
  • Yoshiki Takada
  • Takahiko Sugiura
  • Hidehiko Yamamoto
  • Toshiyuki Sawa
  • Masaaki Kawahara
  • Nobuyuki Katakami
  • Yutaka Ariyoshi
  • Masahiro Fukuoka
Phase II Studies


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.


Amrubicin Small cell lung cancer Anthracycline Previously untreated patients Phase II study 


  1. 1.
    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 983–1018Google Scholar
  2. 2.
    Aisner J (1996) Extensive-disease small-cell lung cancer: the thrill of victory; the agony of defeat. J Clin Oncol 14:658–665PubMedGoogle Scholar
  3. 3.
    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 346:85–91PubMedCrossRefGoogle Scholar
  4. 4.
    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 67:37–43PubMedGoogle Scholar
  5. 5.
    Ishizumi K, Ohashi N, Tanno N (1987) Stereospecific total synthesis of 9-aminoanthracyclines: (+)-9-amino-9-deoxydaunomycin and related compounds. J Org Chem 52:4477–4485CrossRefGoogle Scholar
  6. 6.
    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 80:69–76PubMedGoogle Scholar
  7. 7.
    Morisada S, Yanagi Y, Kashiwazaki Y, Fukui M (1989) Toxicological aspects of a novel 9-aminoanthracycline, SM-5887. Jpn J Cancer Res 80:77–82PubMedGoogle Scholar
  8. 8.
    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 15:219–225PubMedCrossRefGoogle Scholar
  9. 9.
    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 16:121–128PubMedCrossRefGoogle Scholar
  10. 10.
    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 89:1067–1073PubMedGoogle Scholar
  11. 11.
    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 89:1055–1060PubMedGoogle Scholar
  12. 12.
    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 89:1229–1238PubMedGoogle Scholar
  13. 13.
    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 14:361Google Scholar
  14. 14.
    Japan Society for Cancer Therapy (1993) Criteria for the evaluation of the clinical effects of solid cancer chemotherapy. J Jpn Soc Cancer Ther 28:101–130Google Scholar
  15. 15.
    World Health Organization (1979) Handbook for reporting results of cancer treatment (WHO Offst Publication No. 48). World Health Organization, Geneva, SwitzerlandGoogle Scholar
  16. 16.
    Kaplan WH, Meier P (1952) Nonparametric estimation from incomplete observations. J Am Atat Assoc 53:583–612Google Scholar
  17. 17.
    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 10:484–498PubMedGoogle Scholar
  18. 18.
    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 18:1013–1019Google Scholar
  19. 19.
    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 10:1225–1229PubMedGoogle Scholar
  20. 20.
    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 14:2345–2352PubMedGoogle Scholar
  21. 21.
    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 13:1430–1435PubMedGoogle Scholar
  22. 22.
    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 13:326Google Scholar
  23. 23.
    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 5:237–241PubMedGoogle Scholar
  24. 24.
    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 5:283–285PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • Takashi Yana
    • 1
    • 12
    Email author
  • Shunichi Negoro
    • 2
  • Minoru Takada
    • 1
  • Soichiro Yokota
    • 3
  • Yoshiki Takada
    • 4
  • Takahiko Sugiura
    • 5
  • Hidehiko Yamamoto
    • 6
  • Toshiyuki Sawa
    • 7
  • Masaaki Kawahara
    • 8
  • Nobuyuki Katakami
    • 9
  • Yutaka Ariyoshi
    • 10
  • Masahiro Fukuoka
    • 11
  1. 1.Department of Internal MedicineOsaka Prefectural Habikino HospitalHabikinoJapan
  2. 2.Department of Clinical OncologyOsaka City General HospitalOsakaJapan
  3. 3.Department of Internal MedicineNational Toneyama Hospital for Chest DiseasesToyonakaJapan
  4. 4.Department of RadiologyHyogo Medical Center for AdultsAkashiJapan
  5. 5.Department of Internal MedicineAichi Cancer Center HospitalNagoyaJapan
  6. 6.Department of Internal MedicineAso Iizuka HospitalIizukaJapan
  7. 7.Division of Respiratory MedicineGifu Municipal HospitalGifuJapan
  8. 8.Department of Internal MedicineNational Kinki Central Hospital for Chest DiseaseSakaiJapan
  9. 9.Division of Pulmonary MedicineKobe City General HospitalKobeJapan
  10. 10.Department of Internal MedicinePrefectural Aichi HospitalOkazakiJapan
  11. 11.Department of Medical OncologyKinki University School of MedicineOsakasayamaJapan
  12. 12.Division of Respiratory MedicineKKR Otemae HospitalOsakaJapan

Personalised recommendations