Systematic Therapy for Unresectable or Metastatic Soft-Tissue Sarcomas: Past, Present, and Future

Abstract

Unresectable or metastatic disease occurs in 40% to 60% of soft-tissue sarcoma (STS) patients and portends a poor prognosis. For decades, doxorubicin has formed the backbone of systemic treatment, with response rates of approximately 26%. Patients progressing following first-line therapy were left with few proven options. No other cytotoxic chemotherapy agent or combination has demonstrated superiority to doxorubicin. Advances in targeted therapy of STS have been hindered by STS heterogeneity and poorly understood disease biology. Despite challenges, progress has been made in specific STS subtypes. Here, we highlight the challenges, progress, and lessons learned from STS trials published in the last 20 to 25 years.

Serum protein acidic and rich in cysteine (SPARC) as a prognostic marker in soft tissue sarcomas

“…NAB-paclitaxel may act as a “Trojan horse,” with the albumin encapsulation serving to direct the paclitaxel chemotherapeutic agent to tumor cells via binding to SPARC. While taxane monotherapy has been shown to be active primarily in angiosarcoma [25,26], several reports have demonstrated that taxane combination therapy is active in STS (reviewed in [7]). Notably, the combination of docetaxel and gemcitabine has demonstrated superiority over gemcitabine monotherapy in a randomized phase 2 trial in STS [27].…”

Serum protein acidic and rich in cysteine (SPARC) as a prognostic marker in soft tissue sarcomas

“…NAB-paclitaxel may act as a “Trojan horse,” with the albumin encapsulation serving to direct the paclitaxel chemotherapeutic agent to tumor cells via binding to SPARC. While taxane monotherapy has been shown to be active primarily in angiosarcoma [25,26], several reports have demonstrated that taxane combination therapy is active in STS (reviewed in [7]). Notably, the combination of docetaxel and gemcitabine has demonstrated superiority over gemcitabine monotherapy in a randomized phase 2 trial in STS [27].…”

Synovial sarcoma presenting with huge mediastinal mass: a case report and review of literature

“…Although there are no randomized phase III studies to define the most effective modality, patients with unresectable sarcomas are usually treated with systemic chemotherapy and/ or EBRT [14,15]. Because an adequate response to EBRT and chemotherapy may convert an initially unresectable tumor to one that can be resected and potentially cured, the choice of particular type of chemotherapy regimen or of radiotherapy is usually guided by the sarcoma histologic subtype, given the recognized wide variability of response of different STS subtypes to chemotherapy regimens and radiotherapy.…”

Pazopanib in the management of advanced soft tissue sarcomas

“……”

Serum protein acidic and rich in cysteine (SPARC) as a prognostic marker in soft tissue sarcomas

“…NAB-paclitaxel may act as a “Trojan horse,” with the albumin encapsulation serving to direct the paclitaxel chemotherapeutic agent to tumor cells via binding to SPARC. While taxane monotherapy has been shown to be active primarily in angiosarcoma [25,26], several reports have demonstrated that taxane combination therapy is active in STS (reviewed in [7]). Notably, the combination of docetaxel and gemcitabine has demonstrated superiority over gemcitabine monotherapy in a randomized phase 2 trial in STS [27].…”

Synovial sarcoma presenting with huge mediastinal mass: a case report and review of literature

“…Although there are no randomized phase III studies to define the most effective modality, patients with unresectable sarcomas are usually treated with systemic chemotherapy and/ or EBRT [14,15]. Because an adequate response to EBRT and chemotherapy may convert an initially unresectable tumor to one that can be resected and potentially cured, the choice of particular type of chemotherapy regimen or of radiotherapy is usually guided by the sarcoma histologic subtype, given the recognized wide variability of response of different STS subtypes to chemotherapy regimens and radiotherapy.…”

Pazopanib in the management of advanced soft tissue sarcomas

“……”

Serum protein acidic and rich in cysteine (SPARC) as a prognostic marker in soft tissue sarcomas

“…NAB-paclitaxel may act as a “Trojan horse,” with the albumin encapsulation serving to direct the paclitaxel chemotherapeutic agent to tumor cells via binding to SPARC. While taxane monotherapy has been shown to be active primarily in angiosarcoma [25,26], several reports have demonstrated that taxane combination therapy is active in STS (reviewed in [7]). Notably, the combination of docetaxel and gemcitabine has demonstrated superiority over gemcitabine monotherapy in a randomized phase 2 trial in STS [27].…”

Synovial sarcoma presenting with huge mediastinal mass: a case report and review of literature

“…Although there are no randomized phase III studies to define the most effective modality, patients with unresectable sarcomas are usually treated with systemic chemotherapy and/ or EBRT [14,15]. Because an adequate response to EBRT and chemotherapy may convert an initially unresectable tumor to one that can be resected and potentially cured, the choice of particular type of chemotherapy regimen or of radiotherapy is usually guided by the sarcoma histologic subtype, given the recognized wide variability of response of different STS subtypes to chemotherapy regimens and radiotherapy.…”

Pazopanib in the management of advanced soft tissue sarcomas

“……”