Efficacy and safety of doxorubicin–ifosfamide versus gemcitabine–docetaxel as first‐line therapy in advanced nonuterine leiomyosarcoma: A multicenter real‐world study
Nonuterine leiomyosarcoma (NU-LMS) is a rare and biologically distinct subtype of soft tissue sarcoma (STS) with clinical behavior differing from that of uterine leiomyosarcoma. In advanced or metastatic STS, immunotherapy has demonstrated only modest activity, and chemotherapy remains the cornerstone of treatment. However, there is a persistent unmet need for more effective and better-tolerated options in this population. This multicenter, retrospective study included 150 patients with histologically confirmed metastatic NU-LMS who received first-line doxorubicin-ifosfamide (AI) or gemcitabine-docetaxel (GD) at 26 oncology centers in Turkey between 2010 and 2024. The primary endpoint was overall survival (OS). Survival was analyzed using Kaplan-Meier estimates and Cox proportional hazards models. Of 150 patients, 79 received AI and 71 received GD. Median OS for the entire cohort was 21.0 months. Median OS was 22.0 months with AI and 19.1 months with GD (p = .18), median progression-free survival was 7.3 versus 6.1 months (p = .66), and overall response rate was 25.3% versus 29.6% (p = .58), indicating no statistically significant differences in efficacy between the two regimens. Hematologic toxicities were less frequent with GD. AI and GD demonstrated comparable efficacy as first-line regimens for advanced or metastatic NU-LMS, with fewer hematologic toxicities observed for GD. Tumor location may have prognostic implications. These findings support individualized treatment selection and highlight the need for prospective studies in this rare and understudied sarcoma subtype, while the recent LMS-04 trial underscores the importance of future comparisons with doxorubicin-trabectedin to further refine first-line strategies in LMS.
Authors
- Ilgın Koç Kuş (ORCID: https://orcid.org/0000-0001-9797-8037)
- Ali Aytac
- Irem Ugurlu
- Bilgin Demir (ORCID: https://orcid.org/0000-0003-4380-9419)
- Haydar Çağatay Yüksel (ORCID: https://orcid.org/0000-0001-8857-2983)
- Pınar Gürsoy (ORCID: https://orcid.org/0000-0003-1392-6753)
- Zafer Arık (ORCID: https://orcid.org/0000-0002-0598-389X)
- İlhan Hacıbekiroğlu (ORCID: https://orcid.org/0000-0002-0333-7405)
- Alberto Terzi (ORCID: https://orcid.org/0000-0002-2272-0389)
- Aslı Ece Solmaz (ORCID: https://orcid.org/0000-0003-2540-5293)
- İbrahim Akın (ORCID: https://orcid.org/0000-0003-1974-6147)
- Osman Sütçüoğlu (ORCID: https://orcid.org/0000-0003-3835-2741)
- Teoman Şakalar (ORCID: https://orcid.org/0000-0003-2749-9414)
- Esmanur Kaplan
- Fatih Kuş (ORCID: https://orcid.org/0000-0003-1650-154X)
- Ulus Ali Şanlı (ORCID: https://orcid.org/0000-0002-0062-6105)
- Erdem Göker (ORCID: https://orcid.org/0000-0001-6180-713X)
- Ahmet Halil Sevinç (ORCID: https://orcid.org/0000-0003-2965-1782)
- Ertuğrul Bayram (ORCID: https://orcid.org/0000-0001-8713-7613)
- Meltem Baykara (ORCID: https://orcid.org/0000-0003-3291-8134)
- Havva Yesil
- Caner Acar (ORCID: https://orcid.org/0000-0002-9782-6807)
- Tolga Köşeci (ORCID: https://orcid.org/0000-0002-8696-0525)
- Hamit Bal (ORCID: https://orcid.org/0009-0009-6747-8264)
- Cengiz Karaçin (ORCID: https://orcid.org/0000-0002-7310-9328)
- Ahmet Ünlü (ORCID: https://orcid.org/0000-0001-6654-3815)
- Oktay Demirkıran (ORCID: https://orcid.org/0000-0003-1319-9381)
- Elif Şahin (ORCID: https://orcid.org/0000-0002-1976-3951)
- Ahmet Ünsal (ORCID: https://orcid.org/0000-0001-8625-0761)
- Abdullah Sakin (ORCID: https://orcid.org/0000-0003-2538-8569)
- A. Kuś
- Sedat Biter (ORCID: https://orcid.org/0000-0002-1053-0668)
- Salih Tünbekici (ORCID: https://orcid.org/0000-0001-8804-7636)
- Galip Can Uyar (ORCID: https://orcid.org/0000-0002-0698-777X)
- Duygu Özaşkın (ORCID: https://orcid.org/0009-0004-6376-8399)
- Gökhan Şahin (ORCID: https://orcid.org/0000-0003-3980-8034)
- Mustafa Dilek (ORCID: https://orcid.org/0000-0002-2565-6693)
- Ceren Kabaoglu (ORCID: https://orcid.org/0000-0001-5665-911X)
- Elisa Alves Ramos Zin (ORCID: https://orcid.org/0000-0003-1132-2825)
- Mahmut Kara (ORCID: https://orcid.org/0009-0002-3090-8696)
- Atilla Yıldırım
- Alper Coşkun (ORCID: https://orcid.org/0000-0003-2444-6587)
- Ibrahim Tunbekici (ORCID: https://orcid.org/0009-0008-3943-7871)
- Mert Iscı (ORCID: https://orcid.org/0000-0002-7192-6770)
- Gamze Emin (ORCID: https://orcid.org/0000-0002-1549-7326)
- Ceren Mordag
- Hasan Aslanhan (ORCID: https://orcid.org/0009-0006-8091-8760)
Institutions
- Sakarya University (TR)
- Van Yüzüncü Yıl Üniversitesi (TR)
- Dicle University (TR)
- Bursa Uludağ Üni̇versi̇tesi̇ (TR)
- Gümüşhane University (TR)
- Karadeniz Technical University (TR)
- Manisa Celal Bayar University (TR)
- Dokuz Eylül University (TR)
- Istanbul Medipol University (TR)
- Ege University (TR)
- Memorial Ankara Hospital (TR)
- Dr Lütfi Kırdar Kartal Eğitim ve Araştırma Hastanesi (TR)
- Ankara Onkoloji Eğitim ve Araştırma Hastanesi (TR)
- Antalya Eğitim ve Araştırma Hastanesi (TR)
- Medical Park Gaziantep Hospital (TR)
- Hacettepe University Hospital (TR)
- Sakarya Eğitim ve Araştırma Hastanesi (TR)
- Şanlıurfa Mehmet Akif İnan Eğitim ve Araştırma Hastanesi (TR)
- Sağlık Bilimleri Üniversitesi (TR)
- Afyonkarahisar Sağlık Bilimleri Üniversitesi
- Kahramanmaraş Sütçü İmam University (TR)
- Pamukkale University (TR)
- Kocaeli Üniversitesi (TR)
- Afyon Kocatepe University (TR)
- Cukurova University (TR)
- Gaziantep University (TR)
- Adnan Menderes University (TR)
Publication Details
- Journal
- International Journal of Cancer
- Published
- 2025-10-28
- DOI
- https://doi.org/10.1002/ijc.70212
- Primary Topic
- Sarcoma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00