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A Retrospective Analysis of Topotecan Treatment in Small Cell Lung Cancer

Yıl 2025, Cilt: 51 Sayı: 3, 403 - 409, 08.12.2025
https://doi.org/10.32708/uutfd.1742951

Öz

Small cell lung cancer (SCLC) is a subtype of lung cancer known to be associated with smoking and characterized by poor prognosis. Topotecan, a topoisomerase-1 inhibitor, is an important treatment options used in second-line and later settings for SCLC. This study aimed to present our clinical experience with topotecan in the treatment of SCLC patients. We retrospectively reviewed the medical records of 27 patients diagnosed with SCLC who received topotecan treatment between 1 January 2017 and 20 April 2022. The median age was 62 years (range, 37-75). In terms of best treatment response, one patient achieved a partial response, four had stable disease, while disease progression was observed in 22 patients. Kaplan-Meier survival analysis showed a median progression-free survival (PFS) of 2.4 months (95% confidence interval [CI], 1.33-3.47) and a median overall survival (OS) of 3.73 months (95% CI, 1.41-6.05). Patients with liver metastases before topotecan treatment had significantly worse survival outcomes (PFS, Log Rank p=0.009; OS, Log Rank p=0.031). In multivariate Cox regression analysis, liver metastasis prior to treatment was identified as an independent risk factor for both PFS and OS. Treatment-related adverse events of any grade occurred in all patients. Although the results of our study should be interpreted with caution due to its single-center design and limited number of patients, this may be attributed to the use of a weekly topotecan regimen in the majority of patients (85.2%). Larger, multicenter studies are needed to improve survival outcomes and optimize treatment strategies in SCLC.

Kaynakça

  • 1. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024 Jan-Feb;74(1):12-49. doi: 10.3322 /caac.21820. Epub 2024 Jan 17. Erratum in: CA Cancer J Clin. 2024 Mar-Apr;74(2):203.
  • 2. Govindan R, Page N, Morgensztern D, et al. 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. 2006 Oct 1;24(28):4539-4544.
  • 3. Jett JR, Schild SE, Kesler KA, Kalemkerian GP. Treatment of small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013 May;143(5 Suppl):e400S-e419S.
  • 4. Liu SV, Reck M, Mansfield AS, et al. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 2021 Feb 20;39(6):619-630.
  • 5. Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1929-1939.
  • 6. von Pawel J, Schiller JH, Shepherd FA, et al. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol. 1999 Feb;17(2):658-667.
  • 7. Smyth JF, Smith IE, Sessa C, et al. Activity of docetaxel (Taxotere) in small cell lung cancer. The Early Clinical Trials Group of the EORTC. Eur J Cancer. 1994;30A(8):1058-1060.
  • 8. van der Lee I, Smit EF, van Putten JW, et al. Single-agent gemcitabine in patients with resistant small-cell lung cancer. Ann Oncol. 2001 Apr;12(4):557-561.
  • 9. Trigo J, Subbiah V, Besse B, et al. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol. 2020 May;21(5):645-654.
  • 10. Zauderer MG, Drilon A, Kadota K, et al. Trial of a 5-day dosing regimen of temozolomide in patients with relapsed small cell lung cancers with assessment of methylguanine-DNA methyltransferase. Lung Cancer. 2014 Nov;86(2):237-240.
  • 11. Ready NE, Ott PA, Hellmann MD, et al. Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Recurrent Small Cell Lung Cancer: Results From the CheckMate 032 Randomized Cohort. J Thorac Oncol. 2020 Mar;15(3):426-435.
  • 12. Chung HC, Piha-Paul SA, Lopez-Martin J, et al. Pembrolizumab After Two or More Lines of Previous Therapy in Patients With Recurrent or Metastatic SCLC: Results From Topotecan Treatment in Small Cell Lung Cancer the KEYNOTE-028 and KEYNOTE-158 Studies. J Thorac Oncol. 2020 Apr;15(4):618-627.
  • 13.Ahn MJ, Cho BC, Felip E, et al. Tarlatamab for Patients withPreviously Treated Small-Cell Lung Cancer. N Engl J Med.2023 Nov 30;389(22):2063-2075.
  • 14.Ardizzoni A, Hansen H, Dombernowsky P, et al. Topotecan, anew active drug in the second-line treatment of small-cell lungcancer: a phase II study in patients with refractory and sensitivedisease. The European Organization for Research andTreatment of Cancer Early Clinical Studies Group and NewDrug Development Office, and the Lung Cancer CooperativeGroup. J Clin Oncol. 1997 May;15(5):2090-2096.
  • 15.Schiller JH, Kim K, Hutson P, et al. Phase II study of topotecanin patients with extensive-stage small-cell carcinoma of thelung: an Eastern Cooperative Oncology Group Trial. J ClinOncol. 1996;14(8):2345-2352.
  • 16.Schiller JH, Adak S, Cella D, DeVore RF 3rd, Johnson DH.Topotecan versus observation after cisplatin plus etoposide inextensive-stage small-cell lung cancer: E7593--a phase III trialof the Eastern Cooperative Oncology Group. J Clin Oncol.2001;19(8):2114-2122.
  • 17.Spigel DR, Greco FA, Burris HA 3rd, et al. A phase II study ofhigher dose weekly topotecan in relapsed small-cell lungcancer. Clin Lung Cancer. 2011;12(3):187-191.
  • 18.Shah C, Ready N, Perry M, et al. A multi-center phase II studyof weekly topotecan as second-line therapy for small cell lungcancer. Lung Cancer. 2007 Jul;57(1):84-88.
  • 19.von Pawel J, Gatzemeier U, Pujol JL, et al. Phase ii comparatorstudy of oral versus intravenous topotecan in patients withchemosensitive small-cell lung cancer. J Clin Oncol. 2001 Mar 15;19(6):1743-1749.
  • 20.Eckardt JR, von Pawel J, Pujol JL, et al. Phase III study of oralcompared with intravenous topotecan as second-line therapy insmall-cell lung cancer. J Clin Oncol. 2007 May20;25(15):2086-2092.
  • 21.Jotte R, Conkling P, Reynolds C, et al. Randomized phase IItrial of single-agent amrubicin or topotecan as second-line treatment in patients with small-cell lung cancer sensitive tofirst-line platinum-based chemotherapy. J Clin Oncol. 2011 Jan 20;29(3):287-293.
  • 22.Evans TL, Cho BC, Udud K, et al. Cabazitaxel VersusTopotecan in Patients with Small-Cell Lung Cancer withProgressive Disease During or After First-Line Platinum-Based Chemotherapy. J Thorac Oncol. 2015 Aug;10(8):1221-1228.
  • 23.Goto K, Ohe Y, Shibata T, et al. Combined with chemotherapycisplatin, etoposide, and irinotecan versus topotecan alone assecond-line treatment for patients with sensitive relapsed small-cell lung cancer (JCOG0605): a multicentre, open-label, randomized phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1147-1157.
  • 24.Kang JH, Lee KH, Kim DW, et al. A randomized phase 2bstudy comparing the efficacy and safety of belotecan vs.topotecan as monotherapy for sensitive-relapsed small-cell lungcancer. Br J Cancer. 2021 Feb;124(4):713-720. 25.Riemsma R, Simons JP, Bashir Z, Gooch CL, Kleijnen J.Systematic Review of topotecan (Hycamtin) in relapsed smallcell lung cancer. BMC Cancer. 2010 Aug 17;10:436 .
  • 26. von Pawel J. The role of topotecan in treating small cell lungcancer: second-line treatment. Lung Cancer. 2003 Aug;41Suppl 4:S3-8.
  • 27.Pujol JL, Greillier L, Audigier-Valette C, et al. A RandomizedNon-Comparative Phase II Study of Anti-Programmed CellDeath-Ligand 1 Atezolizumab or Chemotherapy as Second-Line Therapy in Patients With Small Cell Lung Cancer: ResultsFrom the IFCT-1603 Trial. J Thorac Oncol. 2019May;14(5):903-913.
  • 28.Pietanza MC, Waqar SN, Krug LM, et al. Randomized,Double-Blind, Phase II Study of Temozolomide inCombination With Either Veliparib or Placebo in Patients WithRelapsed-Sensitive or Refractory Small-Cell Lung Cancer. JClin Oncol. 2018 Aug 10;36(23):2386-2394.
  • 29.Wakuda K, Kenmotsu H, Naito T, et al. Efficacy of rechallengechemotherapy in patients with sensitive relapsed small cell lungcancer. Am J Clin Oncol. 2015 Feb;38(1):28-32.
  • 30.Simos D, Sajjady G, Sergi M, et al. Third-line chemotherapy insmall-cell lung cancer: an international analysis. Clin LungCancer. 2014 Mar;15(2):110-118.

Küçük Hücreli Akciğer Kanserinde Topotekan Tedavisinin Retrospektif Analizi

Yıl 2025, Cilt: 51 Sayı: 3, 403 - 409, 08.12.2025
https://doi.org/10.32708/uutfd.1742951

Öz

Küçük hücreli akciğer kanseri (KHAK), sigara ile ilişkili olduğu bilinen, kötü prognozlu bir akciğer kanseri alt tipidir. Topoizomeraz-1 inhibitörü olan topotekan, KHAK tedavisinde ikinci seçim ve sonrasında kullanılan önemli tedavi seçeneklerinden biridir. Çalışmamızda kliniğimizde takip, tedavi edilen KHAK hastalarının tedavisinde topotekan deneyimimizin aktarılması amaçlanmıştır. Çalışmamızda 1 Ocak 2017 ve 20 Nisan 2022 tarihleri arasında topotekan tedavisi başlanan 27 KHAK tanılı hastanın dosyası retrospektif olarak değerlendirilmiştir. Hastaların medyan yaşı 62 (aralık, 37-75) olarak izlenmiştir. Topotekan tedavisi ile en iyi yanıt durumu değerlendirildiğinde bir hastada kısmi yanıt, dört hastada stabil hastalık izlenirken; 22 hastada progresyon geliştiği görülmüştür. Kaplan-Meier sağkalım analizinde, medyan progresyonsuz sağkalım (PFS) 2,4 ay (%95 güven aralığı [GA], 1,33-3,47), medyan genel sağkalım (OS) 3,73 ay (%95 GA, 1,41-6,05) olarak saptanmıştır. Topotekan tedavisi öncesi karaciğer metastazı olan hastalarda sağkalımların daha kötü olduğu izlenmiştir (PFS, Log Rank p=0,009; OS, Log Rank p=0,031). Çok değişkenli Cox regresyon analizinde, topotekan tedavisi öncesi karaciğer metastazı varlığının PFS ve OS’yi etkileyen bağımsız bir risk faktörü olduğu gösterilmiştir. Herhangi bir derecede tedavi ilişkili advers olay tüm hastalarda gelişmiştir. Çalışmamızda topotekan tedavisi ile literatüre göre medyan PFS ve OS’nin nümerik olarak daha düşük olduğu görülmüştür. Çalışmamızın tek merkez ve sınırlı hasta sayısı içermesi nedeniyle sonuçlarının dikkatle değerlendirilmesi gerektiği düşünülmekle birlikte, bu durumun bir nedeni olarak, çoğu hastada (%85,2) haftalık topotekan rejiminin kullanılması olabileceği düşünülmüştür. KHAK tedavisinde, tedavi seçeneklerinin ve takip stratejilerinin geliştirilerek sağkalımların arttırılması için geniş kapsamlı, çok merkezli çalışmalara ihtiyaç bulunmaktadır.

Kaynakça

  • 1. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024 Jan-Feb;74(1):12-49. doi: 10.3322 /caac.21820. Epub 2024 Jan 17. Erratum in: CA Cancer J Clin. 2024 Mar-Apr;74(2):203.
  • 2. Govindan R, Page N, Morgensztern D, et al. 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. 2006 Oct 1;24(28):4539-4544.
  • 3. Jett JR, Schild SE, Kesler KA, Kalemkerian GP. Treatment of small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013 May;143(5 Suppl):e400S-e419S.
  • 4. Liu SV, Reck M, Mansfield AS, et al. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 2021 Feb 20;39(6):619-630.
  • 5. Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1929-1939.
  • 6. von Pawel J, Schiller JH, Shepherd FA, et al. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol. 1999 Feb;17(2):658-667.
  • 7. Smyth JF, Smith IE, Sessa C, et al. Activity of docetaxel (Taxotere) in small cell lung cancer. The Early Clinical Trials Group of the EORTC. Eur J Cancer. 1994;30A(8):1058-1060.
  • 8. van der Lee I, Smit EF, van Putten JW, et al. Single-agent gemcitabine in patients with resistant small-cell lung cancer. Ann Oncol. 2001 Apr;12(4):557-561.
  • 9. Trigo J, Subbiah V, Besse B, et al. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol. 2020 May;21(5):645-654.
  • 10. Zauderer MG, Drilon A, Kadota K, et al. Trial of a 5-day dosing regimen of temozolomide in patients with relapsed small cell lung cancers with assessment of methylguanine-DNA methyltransferase. Lung Cancer. 2014 Nov;86(2):237-240.
  • 11. Ready NE, Ott PA, Hellmann MD, et al. Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Recurrent Small Cell Lung Cancer: Results From the CheckMate 032 Randomized Cohort. J Thorac Oncol. 2020 Mar;15(3):426-435.
  • 12. Chung HC, Piha-Paul SA, Lopez-Martin J, et al. Pembrolizumab After Two or More Lines of Previous Therapy in Patients With Recurrent or Metastatic SCLC: Results From Topotecan Treatment in Small Cell Lung Cancer the KEYNOTE-028 and KEYNOTE-158 Studies. J Thorac Oncol. 2020 Apr;15(4):618-627.
  • 13.Ahn MJ, Cho BC, Felip E, et al. Tarlatamab for Patients withPreviously Treated Small-Cell Lung Cancer. N Engl J Med.2023 Nov 30;389(22):2063-2075.
  • 14.Ardizzoni A, Hansen H, Dombernowsky P, et al. Topotecan, anew active drug in the second-line treatment of small-cell lungcancer: a phase II study in patients with refractory and sensitivedisease. The European Organization for Research andTreatment of Cancer Early Clinical Studies Group and NewDrug Development Office, and the Lung Cancer CooperativeGroup. J Clin Oncol. 1997 May;15(5):2090-2096.
  • 15.Schiller JH, Kim K, Hutson P, et al. Phase II study of topotecanin patients with extensive-stage small-cell carcinoma of thelung: an Eastern Cooperative Oncology Group Trial. J ClinOncol. 1996;14(8):2345-2352.
  • 16.Schiller JH, Adak S, Cella D, DeVore RF 3rd, Johnson DH.Topotecan versus observation after cisplatin plus etoposide inextensive-stage small-cell lung cancer: E7593--a phase III trialof the Eastern Cooperative Oncology Group. J Clin Oncol.2001;19(8):2114-2122.
  • 17.Spigel DR, Greco FA, Burris HA 3rd, et al. A phase II study ofhigher dose weekly topotecan in relapsed small-cell lungcancer. Clin Lung Cancer. 2011;12(3):187-191.
  • 18.Shah C, Ready N, Perry M, et al. A multi-center phase II studyof weekly topotecan as second-line therapy for small cell lungcancer. Lung Cancer. 2007 Jul;57(1):84-88.
  • 19.von Pawel J, Gatzemeier U, Pujol JL, et al. Phase ii comparatorstudy of oral versus intravenous topotecan in patients withchemosensitive small-cell lung cancer. J Clin Oncol. 2001 Mar 15;19(6):1743-1749.
  • 20.Eckardt JR, von Pawel J, Pujol JL, et al. Phase III study of oralcompared with intravenous topotecan as second-line therapy insmall-cell lung cancer. J Clin Oncol. 2007 May20;25(15):2086-2092.
  • 21.Jotte R, Conkling P, Reynolds C, et al. Randomized phase IItrial of single-agent amrubicin or topotecan as second-line treatment in patients with small-cell lung cancer sensitive tofirst-line platinum-based chemotherapy. J Clin Oncol. 2011 Jan 20;29(3):287-293.
  • 22.Evans TL, Cho BC, Udud K, et al. Cabazitaxel VersusTopotecan in Patients with Small-Cell Lung Cancer withProgressive Disease During or After First-Line Platinum-Based Chemotherapy. J Thorac Oncol. 2015 Aug;10(8):1221-1228.
  • 23.Goto K, Ohe Y, Shibata T, et al. Combined with chemotherapycisplatin, etoposide, and irinotecan versus topotecan alone assecond-line treatment for patients with sensitive relapsed small-cell lung cancer (JCOG0605): a multicentre, open-label, randomized phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1147-1157.
  • 24.Kang JH, Lee KH, Kim DW, et al. A randomized phase 2bstudy comparing the efficacy and safety of belotecan vs.topotecan as monotherapy for sensitive-relapsed small-cell lungcancer. Br J Cancer. 2021 Feb;124(4):713-720. 25.Riemsma R, Simons JP, Bashir Z, Gooch CL, Kleijnen J.Systematic Review of topotecan (Hycamtin) in relapsed smallcell lung cancer. BMC Cancer. 2010 Aug 17;10:436 .
  • 26. von Pawel J. The role of topotecan in treating small cell lungcancer: second-line treatment. Lung Cancer. 2003 Aug;41Suppl 4:S3-8.
  • 27.Pujol JL, Greillier L, Audigier-Valette C, et al. A RandomizedNon-Comparative Phase II Study of Anti-Programmed CellDeath-Ligand 1 Atezolizumab or Chemotherapy as Second-Line Therapy in Patients With Small Cell Lung Cancer: ResultsFrom the IFCT-1603 Trial. J Thorac Oncol. 2019May;14(5):903-913.
  • 28.Pietanza MC, Waqar SN, Krug LM, et al. Randomized,Double-Blind, Phase II Study of Temozolomide inCombination With Either Veliparib or Placebo in Patients WithRelapsed-Sensitive or Refractory Small-Cell Lung Cancer. JClin Oncol. 2018 Aug 10;36(23):2386-2394.
  • 29.Wakuda K, Kenmotsu H, Naito T, et al. Efficacy of rechallengechemotherapy in patients with sensitive relapsed small cell lungcancer. Am J Clin Oncol. 2015 Feb;38(1):28-32.
  • 30.Simos D, Sajjady G, Sergi M, et al. Third-line chemotherapy insmall-cell lung cancer: an international analysis. Clin LungCancer. 2014 Mar;15(2):110-118.
Toplam 29 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular İç Hastalıkları
Bölüm Araştırma Makalesi
Yazarlar

Alper Coşkun 0000-0003-2444-6587

Eyüp Çoban 0000-0002-1618-8082

Seda Sali 0000-0001-8575-5477

Süreyya Sarıhan 0000-0003-4816-5798

Ahmet Bilgehan Şahin 0000-0002-7846-0870

Adem Deligönül 0000-0002-3669-6391

Erdem Çubukçu 0000-0002-0070-0889

Türkkan Evrensel 0000-0002-9732-5340

Gönderilme Tarihi 15 Temmuz 2025
Kabul Tarihi 23 Eylül 2025
Yayımlanma Tarihi 8 Aralık 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 51 Sayı: 3

Kaynak Göster

AMA Coşkun A, Çoban E, Sali S, vd. A Retrospective Analysis of Topotecan Treatment in Small Cell Lung Cancer. Uludağ Tıp Derg. Aralık 2025;51(3):403-409. doi:10.32708/uutfd.1742951

ISSN: 1300-414X, e-ISSN: 2645-9027

Uludağ Üniversitesi Tıp Fakültesi Dergisi "Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License" ile lisanslanmaktadır.


Creative Commons License
Journal of Uludag University Medical Faculty is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

2023