nach oben

Erschienen in:

12.12.2017 | Original Article

A phase II trial of Ifosfamide combination with recommended supportive therapy for recurrent SCLC in second-line and heavily treated setting

verfasst von: Ichidai Tanaka, Kenji Kawada, Masahiro Morise, Tetsunari Hase, Hiroaki Hayashi, Akihiko Sokai, Asuki Fukatsu, Masashi Kondo, Fumio Nomura, Yoshinori Hasegawa

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 2/2018

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The response rate of ifosfamide (IFM) monotherapy for small-cell lung cancer (SCLC) is reported as 42.4% in Japanese package insert. However, these efficacy data are based on clinical studies conducted in 1970s. This phase II study evaluated the efficacy and safety of IFM combination with recommended current supportive therapy for recurrent SCLC in second-line and heavily treated setting.

Methods

Recurrent SCLC patients pretreated with one to three prior regimens received IFM monotherapy (1.5 g/m² for 3 days every 3 weeks). Treatment was continued until disease progression or unacceptable toxicity. The primary end point was objective response rate.

Results

Twelve patients were enrolled in the study from June 2009 to January 2013. The study was early terminated at interim analysis due to futility stop. Patient characteristics were as follows: median age was 65 years, 11 were males (91.7%) and eight (66.7%) and four (33.3%) were Performance Status 0 and 1, respectively. Four patients (33.3%) enrolled in second-line setting were all refractory relapse SCLC and 8 (66.7%) were heavily treated patients. No patient showed objective response. Stable disease was observed in 3 patients. Median progression-free survival and overall survival were 0.9 months (95% CI, 0.3–1.5) and 4.8 months (95% CI, 1.6–9.9), respectively. Although one grade 4 amylase increase possibly related to IFM was observed, toxicity profile was totally favorable.

Conclusions

IFM monotherapy should not be used for refractory relapse or heavily treated SCLC, and no further investigation is required in these populations.

Toyoda Y, Nakayama T, Ioka A et al (2008) Trends in lung cancer incidence by histological type in Osaka, Japan. Jpn J Clin Oncol 38:534–539CrossRefPubMedPubMedCentral

Govindan R, Page N, Morgensztern D et al (2006) Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol 24:4539–4544CrossRefPubMed

Ardizzoni A, Hansen H, Dombernowsky P et al (1997) 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 15:2090–2096CrossRefPubMed

O’Brien ME, Ciuleanu TE, Tsekov H et al (2006) Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol 24:5441–5447CrossRefPubMed

Onoda S, Masuda N, Seto T et al (2006) Phase II trial of amrubicin for treatment of refractory or relapsed small-cell lung cancer: Thoracic Oncology Research Group Study 0301. J Clin Oncol 24:5448–5453CrossRefPubMed

Inoue A, Sugawara S, Yamazaki K et al (2008) Randomized phase II trial comparing amrubicin with topotecan in patients with previously treated small-cell lung cancer: North Japan Lung Cancer Study Group Trial 0402. J Clin Oncol 26:5401–5406CrossRefPubMed

Ettinger DS, Jotte R, Lorigan P et al (2010) Phase II study of amrubicin as second-line therapy in patients with platinum-refractory small-cell lung cancer. J Clin Oncol 28:2598–603CrossRefPubMed

Masuda N, Fukuoka M, Kusunoki Y et al (1992) CPT-11: a new derivative of camptothecin for the treatment of refractory or relapsed small-cell lung cancer. J Clin Oncol 10:1225–1229CrossRefPubMed

Issels RD, Prenninger SW, Nagele A et al (1990) Ifosfamide plus etoposide combined with regional hyperthermia in patients with locally advanced sarcomas: a phase II study. J Clin Oncol 8:1818–1829CrossRefPubMed

10.

Lund B, Hansen M, Hansen OP et al (1990) Combined high-dose carboplatin and cisplatin, and ifosfamide in previously untreated ovarian cancer patients with residual disease. J Clin Oncol 8:1226–1230CrossRefPubMed

11.

Maki Y, Tsushima T, Nasu Y et al (1998) Combination chemotherapy with cis-platinum and ifosfamide for hormone unresponsive prostate cancer. Nippon Hinyokika Gakkai Zasshi 89:657–664PubMed

12.

Kaku H, Saika T, Tsushima T et al (2006) Combination chemotherapy with estramustine phosphate, ifosfamide and cisplatin for hormone-refractory prostate cancer. Acta Med Okayama 60:43–49PubMed

13.

Turner AR, Duong CD, Good DJ (2003) Methylene blue for the treatment and prophylaxis of ifosfamide-induced encephalopathy. Clin Oncol (R Coll Radiol) 15:435–439CrossRef

14.

Elias AD, Eder JP, Shea T et al (1990) High-dose ifosfamide with mesna uroprotection: a phase I study. J Clin Oncol 8:170–178CrossRefPubMed

15.

Mukouda K, Morikawa E, Hasegawa K et al (1983) Ifosfamide in the treatment of small cell carcinoma of the lung. Gan To Kagaku Ryoho 10:1293–1298PubMed

16.

Eckardt JR, von Pawel J, Pujol JL et al (2007) Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol 25:2086–2092CrossRefPubMed

17.

von Pawel J, Schiller JH, Shepherd FA et al (1999) Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol 17:658–667CrossRef

18.

Solomon BJ, Mok T, Kim DW et al (2014) First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med 371:2167–2177CrossRefPubMed

19.

Maemondo M, Inoue A, Kobayashi K et al (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362:2380–2388CrossRefPubMed

20.

Mitsudomi T, Morita S, Yatabe Y et al (2010) Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 11:121–128CrossRefPubMed

21.

Ready NE, Pang HH, Gu L et al (2015) Chemotherapy with or without maintenance sunitinib for untreated extensive-stage small-cell lung cancer: a randomized, double-blind, placebo-controlled phase II study-CALGB 30504 (alliance). J Clin Oncol 33:1660–1665CrossRefPubMedPubMedCentral

22.

Pujol JL, Lavole A, Quoix E et al (2015) Randomized phase II-III study of bevacizumab in combination with chemotherapy in previously untreated extensive small-cell lung cancer: results from the IFCT-0802 trialdagger. Ann Oncol 26:908–914CrossRefPubMed

23.

Lo-Coco F, Avvisati G, Vignetti M et al (2013) Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med 369:111–21CrossRefPubMed

Titel: A phase II trial of Ifosfamide combination with recommended supportive therapy for recurrent SCLC in second-line and heavily treated setting
verfasst von: Ichidai Tanaka
Kenji Kawada
Masahiro Morise
Tetsunari Hase
Hiroaki Hayashi
Akihiko Sokai
Asuki Fukatsu
Masashi Kondo
Fumio Nomura
Yoshinori Hasegawa
Publikationsdatum: 12.12.2017
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 2/2018
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-017-3497-0

Springer Medizin

A phase II trial of Ifosfamide combination with recommended supportive therapy for recurrent SCLC in second-line and heavily treated setting