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Efficacy and safety of ifosfamide in combination with carboplatin and etoposide in small cell lung cancer

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Abstract

Purpose

Ifosfamide, a potent alkylating agent, is rarely incorporated into small cell lung cancer (SCLC) treatment. The aim of this study was to assess the efficacy and safety of ifosfamide in combination with carboplatin and etoposide (ICE) in previously untreated patients with SCLC.

Methods

From January 2002 to January 2014, we consecutively enrolled 69 patients with SCLC who were treated with ICE as initial chemotherapy at Kangbuk Samsung Hospital. The modified ICE regimen consists of ifosfamide 1200 mg/m2/day on days 1, 2, and 3 with mesna, etoposide 80 mg/m2/day on days 1, 2, and 3, and carboplatin AUC 6 on day 1. Treatment was repeated every 3 weeks and continued for up to nine cycles. Response assessments were performed every three cycles with computed tomography.

Results

Among 69 patients with SCLC, the median age was 69 years (range 51–88 years). Sixteen (23 %) patients had limited disease (LD), and 53 (77 %) had extensive disease (ED). The overall response rate was 73 %. Stable disease rate was 20 %. The median overall survival was 11.3 months [95 % confidence interval (CI) 8.9–14.1] in the overall population, 20.6 months (95 % CI 14.2–21.2) for LD and 9.1 months (95 % CI 7.8–11.6) for ED. The median number of administered cycles was 6 (range 1–9). Grade ≥3 hematological toxicities included neutropenia (34 %), anemia (59 %), and thrombocytopenia (31 %). Grade ≥3 non-hematological toxicities included peripheral neuropathy in 2 %.

Conclusion

In chemonaïve patients with SCLC, modified ICE is well tolerated and shows favorable efficacy.

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References

  1. Buccheri G, Ferrigno D (2004) Prognostic factors of small cell lung cancer. Hematol Oncol Clin North Am 18(2):445–460. doi:10.1016/j.hoc.2003.12.011

    Article  PubMed  Google Scholar 

  2. Johnson BE, Janne PA (2004) Basic treatment considerations using chemotherapy for patients with small cell lung cancer. Hematol Oncol Clin North Am 18(2):309–322. doi:10.1016/j.hoc.2003.12.008

    Article  PubMed  Google Scholar 

  3. Govindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahiotis A, Spitznagel EL, Piccirillo J (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(28):4539–4544. doi:10.1200/jco.2005.04.4859

    Article  PubMed  Google Scholar 

  4. Chua YJ, Steer C, Yip D (2004) Recent advances in management of small-cell lung cancer. Cancer Treat Rev 30(6):521–543. doi:10.1016/j.ctrv.2004.06.003

    Article  CAS  PubMed  Google Scholar 

  5. Kurup A, Hanna NH (2004) Treatment of small cell lung cancer. Crit Revi Oncol Hematol 52(2):117–126. doi:10.1016/j.critrevonc.2004.08.005

    Article  Google Scholar 

  6. Simon GR, Turrisi A (2007) Management of small cell lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 132(3 Suppl):324s–339s. doi:10.1378/chest.07-1385

    Article  CAS  PubMed  Google Scholar 

  7. Fleming RA (1997) An overview of cyclophosphamide and ifosfamide pharmacology. Pharmacotherapy 17(5 Pt 2):146s–154s

    CAS  PubMed  Google Scholar 

  8. Thatcher N, Qian W, Clark PI, Hopwood P, Sambrook RJ, Owens R, Stephens RJ, Girling DJ (2005) Ifosfamide, carboplatin, and etoposide with midcycle vincristine versus standard chemotherapy in patients with small-cell lung cancer and good performance status: clinical and quality-of-life results of the British Medical Research Council multicenter randomized LU21 trial. J Clin Oncol 23(33):8371–8379. doi:10.1200/jco.2004.00.9969

    Article  CAS  PubMed  Google Scholar 

  9. Loehrer PJ Sr, Ansari R, Gonin R, Monaco F, Fisher W, Sandler A, Einhorn LH (1995) Cisplatin plus etoposide with and without ifosfamide in extensive small-cell lung cancer: a Hoosier Oncology Group study. J Clin Oncol 13(10):2594–2599

    CAS  PubMed  Google Scholar 

  10. Hand S, Baker J, Smith AP, Macbeth FR (2002) Outpatient intensive chemotherapy for small cell lung cancer: five years experience of modified ‘ICE’ ifosfamide carboplatin and etoposide. Clin Oncol (R Coll Radiol) 14(5):367–371

    Article  CAS  Google Scholar 

  11. Smith IE, Perren TJ, Ashley SA, Woodiwiss J, Forgeson GV, Yarnold JR, Ford HT (1990) Carboplatin, etoposide, and ifosfamide as intensive chemotherapy for small-cell lung cancer. J Clin Oncol 8(5):899–905

    CAS  PubMed  Google Scholar 

  12. Pujol JL, Daures JP, Riviere A, Quoix E, Westeel V, Quantin X, Breton JL, Lemarie E, Poudenx M, Milleron B, Moro D, Debieuvre D, Le Chevalier T (2001) Etoposide plus cisplatin with or without the combination of 4′-epidoxorubicin plus cyclophosphamide in treatment of extensive small-cell lung cancer: a French Federation of Cancer Institutes multicenter phase III randomized study. J Natl Cancer Inst 93(4):300–308

    Article  CAS  PubMed  Google Scholar 

  13. Leyvraz S, Pampallona S, Martinelli G, Ploner F, Perey L, Aversa S, Peters S, Brunsvig P, Montes A, Lange A, Yilmaz U, Rosti G (2008) A threefold dose intensity treatment with ifosfamide, carboplatin, and etoposide for patients with small cell lung cancer: a randomized trial. J Natl Cancer Inst 100(8):533–541. doi:10.1093/jnci/djn088

    Article  CAS  PubMed  Google Scholar 

  14. Kallogjeri D, Piccirillo JF, Spitznagel EL Jr, Steyerberg EW (2012) Comparison of Scoring Methods for ACE-27: Simpler Is Better. J Geriatr Oncol 3(3):238–245. doi:10.1016/j.jgo.2012.01.006

    Article  PubMed Central  PubMed  Google Scholar 

  15. Jiang L, Yang KH, Guan QL, Mi DH, Wang J (2012) Cisplatin plus etoposide versus other platin-based regimens for patients with extensive small-cell lung cancer: a systematic review and meta-analysis of randomised, controlled trials. Intern Med J 42(12):1297–1309. doi:10.1111/j.1445-5994.2012.02821.x

    Article  CAS  PubMed  Google Scholar 

  16. Noda K, Nishiwaki Y, Kawahara M, Negoro S, Sugiura T, Yokoyama A, Fukuoka M, Mori K, Watanabe K, Tamura T, Yamamoto S, Saijo N, Japan Clinical Oncology G (2002) Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med 346(2):85–91. doi:10.1056/NEJMoa003034

    Article  CAS  PubMed  Google Scholar 

  17. Lee SM, James LE, Qian W, Spiro S, Eisen T, Gower NH, Ferry DR, Gilligan D, Harper PG, Prendiville J, Hocking M, Rudd RM (2009) Comparison of gemcitabine and carboplatin versus cisplatin and etoposide for patients with poor-prognosis small cell lung cancer. Thorax 64(1):75–80. doi:10.1136/thx.2007.093872

    Article  CAS  PubMed  Google Scholar 

  18. Niell HB, Herndon JE 2nd, Miller AA, Watson DM, Sandler AB, Kelly K, Marks RS, Perry MC, Ansari RH, Otterson G, Ellerton J, Vokes EE, Green MR, Cancer Leukemia G (2005) Randomized phase III intergroup trial of etoposide and cisplatin with or without paclitaxel and granulocyte colony-stimulating factor in patients with extensive-stage small-cell lung cancer: Cancer and Leukemia Group B Trial 9732. J Clin Oncol 23(16):3752–3759. doi:10.1200/JCO.2005.09.071

    Article  CAS  PubMed  Google Scholar 

  19. Mavroudis D, Papadakis E, Veslemes M, Tsiafaki X, Stavrakakis J, Kouroussis C, Kakolyris S, Bania E, Jordanoglou J, Agelidou M, Vlachonicolis J, Georgoulias V, Greek Lung Cancer Cooperative G (2001) A multicenter randomized clinical trial comparing paclitaxel-cisplatin-etoposide versus cisplatin-etoposide as first-line treatment in patients with small-cell lung cancer. Ann Oncol 12(4):463–470

    Article  CAS  PubMed  Google Scholar 

  20. Eckardt JR, von Pawel J, Papai Z, Tomova A, Tzekova V, Crofts TE, Brannon S, Wissel P, Ross G (2006) Open-label, multicenter, randomized, phase III study comparing oral topotecan/cisplatin versus etoposide/cisplatin as treatment for chemotherapy-naive patients with extensive-disease small-cell lung cancer. J Clin Oncol 24(13):2044–2051. doi:10.1200/JCO.2005.03.3332

    Article  CAS  PubMed  Google Scholar 

  21. Loehrer PJ Sr (1996) The role of ifosfamide in small cell lung cancer. Semin Oncol 23(3 Suppl 7):40–44

    CAS  PubMed  Google Scholar 

  22. Thatcher N, Lind M, Stout R, Payne C, Carroll KB, Campbell C, Moussalli H (1989) Carboplatin, ifosfamide and etoposide with mid-course vincristine and thoracic radiotherapy for ‘limited’ stage small cell carcinoma of the bronchus. Br J Cancer 60(1):98–101

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors wish to thank Haejeung Kim, RN, for assistance of data collection.

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    Authors and Affiliations

    1. Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29, Saemunan-ro, Jongno-gu, Seoul, 110-746, Korea

      Hyo-Sun Lee, Yun-Gyoo Lee, Dong-Hoe Koo, Sukjoong Oh, Jae-Uk Song, Seong Yong Lim, Si-young Lim & Seung-Sei Lee

    2. Department of Radiation Oncology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

      Heerim Nam

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    1. Hyo-Sun Lee
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    Hyo-Sun Lee and Yun-Gyoo Lee have contributed equally to this work.

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    Lee, HS., Lee, YG., Koo, DH. et al. Efficacy and safety of ifosfamide in combination with carboplatin and etoposide in small cell lung cancer. Cancer Chemother Pharmacol 76, 933–937 (2015). https://doi.org/10.1007/s00280-015-2864-y

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