Optimizing Systemic Therapy for Advanced Sarcomas: Outcomes With Gemcitabine, Docetaxel, Cisplatin, and Everolimus in a Retrospective Single-Center Study

Abstract

Background: Advanced sarcomas have limited treatment options. Gemcitabine and docetaxel (GD) regimen showed efficacy in soft tissue sarcomas (STSs) in phase II studies but failed in first-line phase III trial. Adding cisplatin to GD showed efficacy in other types of cancer. mTOR pathway has been shown to play a role in resistance to these drugs. Inflammatory biomarkers have been identified as potential prognostic indicators in various malignancies, but their role in patients with advanced sarcomas is not clear.

Methods: We retrospectively enrolled 77 patients with advanced or metastatic sarcomas (STSs, n = 71; bone sarcomas, n = 6) receiving a novel combination with gemcitabine-gemcitabine/docetaxel/cisplatin plus everolimus (G-GDC + E). Primary endpoints included overall survival (OS) and progression-free survival (PFS). Inflammatory biomarkers were calculated, and their prognostic influence was evaluated.

Results: The median OS and PFS were 16.8 months (95% CI, 13.6-23.9) and 5.4 months (95% CI, 4.3-8.3), respectively. Undifferentiated pleomorphic sarcoma/myxofibrosarcoma (UPS/MFS) demonstrated superior PFS compared to round cell sarcoma/translocation-related sarcoma (7.8 vs. 3.6 months, p = 0.009) and bone sarcoma (7.8 vs. 2.3 months, p < 0.001). Eastern Cooperative Oncology Group Performance Status ≥ 2, unfavorable histology (round cell sarcoma/translocation-related sarcoma and bone sarcoma), lower albumin level, and lymphocyte-to-monocyte ratio < 2.7 were independent predictors of OS. Grade 3-4 toxicities included neutropenia (68.8%), thrombocytopenia (59.7%), anemia (49.4%), diarrhea (18.2%), and skin toxicities (28.6%).

Conclusions: G-GDC + E demonstrates histology-specific efficacy in advanced/metastatic sarcomas, with substantial hematologic toxicity (Grade 3-4 thrombocytopenia 59.7%, neutropenia 68.8%) and notable non-hematologic events (Grade 3-4 diarrhea 18.2%, skin reactions 28.6%), all controllable with close monitoring, dose modifications and supportive care. Inflammatory biomarkers provide independent prognostic values.

Keywords: cisplatin; docetaxel; everolimus; gemcitabine; sarcoma; systemic inflammation biomarkers.