Phase II trial of ifosfamide in combination with the VEGFR inhibitor sorafenib in advanced soft tissue sarcoma: a Spanish group for research on sarcomas (GEIS) study
Por:
del Muro, XG, Maurel, J, Trufero, JM, Lavernia, J, Pousa, AL, de las Penas, R, Cubedo, R, Berros, JP, Herraez, AC, de Juan, A, Broto, JM
Publicada:
1 jun 2018
Resumen:
Background Sorafenib is a potent targeted-therapy that blockades angiogenesis and has demonstrated activity against some sarcoma subtypes. Preclinical studies suggested that treatment with sorafenib plus cytotoxic agents could result in additive efficacy. Methods Patients with advanced soft tissue sarcoma, with or without anthracycline pretreatment were included. Patients received oral sorafenib 400 mg twice daily starting on Day +2, ifosfamide 2.0 g/m2 iv infusion lasting 4 h on days 1. 2 and 3 with concurrent mesna 400 mg/m(2) every three weeks until disease progression or unacceptable toxicity or up to a maximum of 6 cycles of ifosfamide (sorafenib could be continued until progressive disease or unacceptable toxicity). Primary objective was progression-free rate (PFR) at 3 and 6 months; secondary objectives were overall response rate (ORR), Progression-free survival (PFS), Overall survival (OS) and safety. This article reports the phase II part of a phase I/II clinical trial. Results Thirty-five patients were enrolled. PFR at 3 and 6 months was 66% (95% CI 48-81) and 37% (95% CI 22-55). Six patients (17%) achieved partial response and 17 (49%) stable disease. Median PFS was 4.8 months (CI 95% 1.94-6.36) and overall survival 16.2 months (95% CI 8.75-NA). Conclusion Treatment with sorafenib plus ifosfamide achieved a significant clinical benefit with an acceptable safety profile in patients with advanced soft tissue sarcoma resistant to anthracyclines, which warrants a more detailed study in randomized clinical trials.
Filiaciones:
del Muro, XG:
Inst Catala Oncol Hosp, Barcelona, Spain
Maurel, J:
Univ Barcelona, Hosp Clin, IDIBAPS, Barcelona, Spain
Trufero, JM:
Hosp Miguel Servet, Zaragoza, Spain
Lavernia, J:
Inst Valenciano Oncol, Valencia, Spain
Pousa, AL:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
de las Penas, R:
Hosp Prov Castellon, Castellon de La Plana, Spain
Cubedo, R:
Hosp Puerta Hierro, Madrid, Spain
Berros, JP:
Hosp Gen Asturias, Madrid, Spain
Herraez, AC:
Hosp Clin Madrid, Madrid, Spain
de Juan, A:
Hosp Marques Valdecilla, Santander, Spain
Broto, JM:
Hosp Virgen Rocio, Seville, Spain
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