Outcomes of patients (pts) with advanced soft-tissue sarcomas (STS) treated in clinical trials (CTs) versus expanded access programs (EAPs): A decade of experience with single-agent trabectedin (Tr).

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. 10029-10029 ◽  
Author(s):  
G. D. Demetri ◽  
J. Blay ◽  
P. Schoffski ◽  
R. G. Maki ◽  
A. J. Yovine ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Soft Tissue ◽  
Single Agent ◽  
Soft Tissue Sarcomas ◽  
Expanded Access ◽  
Access Programs

scholarly journals The Role of Natural Killer Cells in Soft Tissue Sarcoma: Prospects for Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3865
Author(s):  
Tânia Fortes-Andrade ◽  
Jani Sofia Almeida ◽  
Luana Madalena Sousa ◽  
Manuel Santos-Rosa ◽  
Paulo Freitas-Tavares ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Soft Tissue ◽  
Nk Cells ◽  
Nk Cell ◽  
Malignant Tumors ◽  
Soft Tissue Sarcomas ◽  
Good Prognosis ◽  
Regulatory Pathways ◽  
Immunological Profile ◽  
Study Support

Soft-tissue sarcomas (STS) represent about 80% of sarcomas, and are a heterogeneous group of rare and malignant tumors. STS arise from mesenchymal tissues and can grow into structures such as adipose tissue, muscles, nervous tissue and blood vessels. Morphological evaluation has been the standard model for the diagnosis of sarcomas, and even in samples with similar characteristics, they present a diversity in cytogenetic and genetic sequence alterations, which further increases the diversity of sarcomas. This variety is one of the main challenges for the classification and understanding of STS patterns, as well as for their respective treatments, which further decreases patient survival (<5 years). Despite some studies, little is known about the immunological profile of STS. As for the immunological profile of STS in relation to NK cells, there is also a shortage of studies. Observations made in solid tumors show that the infiltration of NK cells in tumors is associated with a good prognosis of the disease. Notwithstanding the scarcity of studies to characterize NK cells, their receptors, and ligands in STS, it is noteworthy that the progression of these malignancies is associated with altered NK phenotypes. Despite the scarcity of information on the function of NK cells, their phenotypes and their regulatory pathways in STS, the findings of this study support the additional need to explore NK cell-based immunotherapy in STS further. Some clinical trials, very tentatively, are already underway. STS clinical trials are still the basis for adoptive NK-cell and cytokine-based therapy.

Role of New Chemotherapy Agents in Soft Tissue Sarcoma

2005 ◽  
Vol 3 (2) ◽  
pp. 198-205
Author(s):  
Margaret von Mehren
Keyword(s):  
Soft Tissue ◽  
Single Agent ◽  
Growth Factor Receptor ◽  
Soft Tissue Sarcomas ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Cell Cycle Activation ◽  
Metastatic Gist ◽  
Chemotherapy Agents

Medical management of soft tissue sarcomas (STS) has been restricted by the limited availability of active drugs. A plethora of new oncologic agents are now available, many of which have specific therapeutic targets. Gemcitabine and docetaxel is a combination of drugs that have limited single-agent activity. Yondelis, a novel chemotherapeutic that binds DNA and functions partially by inhibiting transcription, is being tested alone and in combination with doxorubicin. Inhibitors of mTOR, a serine/threonine kinase that regulates cell cycle activation and cell growth, are also being tested. Growth factor receptor inhibitors are being evaluated in a variety of sarcomas that have been found to express the targets. In addition, a variety of agents are being assessed in gastrointestinal stromal tumors (GIST). Single agents and agents combined with imatinib are being tested in imatinib-refractory and in metastatic GIST. The increased use of targeted agents underscores the need for understanding sarcoma biology.

Randomized comparison of three adriamycin regimens for metastatic soft tissue sarcomas.

1987 ◽  
Vol 5 (6) ◽  
pp. 840-850 ◽  
Author(s):  
E C Borden ◽  
D A Amato ◽  
C Rosenbaum ◽  
H T Enterline ◽  
M J Shiraki ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Single Agent ◽  
Soft Tissue Sarcomas ◽  
Hematologic Toxicity ◽  
Treatment Results ◽  
Response Frequency ◽  
Final Treatment ◽  
Subjective Judgement ◽  
Impact On Survival ◽  
The Individual

This study addressed two major questions regarding therapeutic use of Adriamycin ([Adr] Adria Laboratories, Columbus, OH) in adult soft tissue sarcomas: the influence of dosing schedule and the value of adding imidazole carboxamide (DTIC) to Adr. Patients with objectively measurable metastatic soft tissue sarcomas were randomized to Adr 70 mg/m2 intravenously (IV) day 1 and every 3 weeks (94 patients); Adr 20 mg/m2 IV day 1, 2, and 3, and 15 mg/m2 IV day 8 and weekly thereafter (89 patients); and Adr 60 mg/m2 IV day 1 and DTIC 250 mg/m2 days 1 to 5, repeated every 3 weeks (92 patients). The regimens using Adr as a single agent resulted in an equivalent response frequency (18% and 16%) and survival (median, 8.0 and 8.4 months). DTIC significantly increased (P less than .02) the overall response frequency of Adr to 30%. However, DTIC did not influence survival (median, 8.0 months) or increase the number of complete responses. The toxicities of the two single-agent regimens differed: Adr weekly resulted in more stomatitis (P = .09) and less hematologic toxicity (P less than .05). DTIC resulted in substantially increased toxicity, primarily gastrointestinal (P less than .002); overall, 98% of patients receiving Adr-DTIC experienced moderate or worse toxicity. To decrease the potential for error in interpretation of treatment results, histopathological confirmation of diagnosis was undertaken by a panel of reference pathologists; pathology slides were submitted on 97% of entered patients. The on-study clinical diagnosis was affirmed in 199 of 316 patients (63%) with a final review. In 23% of patients, the panel agreed with the diagnosis of soft tissue sarcoma, but not with the type. In 14%, the panel concluded that a diagnosis of mesenchymal malignancy could not be affirmed. Final treatment results were based on the 275 pathologically confirmed, eligible patients. The most common histological subtype entered was leiomyosarcoma (99 patients). The response to Adr-DTIC of this subtype was higher (44%) than that of any other subtype. However, this difference alone was not responsible for the overall superiority of the combination. This confirmed that the combination of DTIC plus Adr adds to the response rate of Adr alone in soft tissue sarcomas. Whether the increased response frequency, without an impact on survival, is worth the significantly greater toxicity remains a subjective judgement that must be made within the context of the individual patient.

Cellular DNA content and prognosis of high-grade soft tissue sarcoma: the Scandinavian Sarcoma Group experience.

1990 ◽  
Vol 8 (3) ◽  
pp. 538-547 ◽  
Author(s):  
T A Alvegard ◽  
N O Berg ◽  
B Baldetorp ◽  
M Fernö ◽  
D Killander ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Soft Tissue ◽  
Dna Content ◽  
Nuclear Dna ◽  
Single Agent ◽  
Soft Tissue Sarcomas ◽  
Nuclear Dna Content ◽  
High Grade ◽  
Dna Aneuploidy

The nuclear DNA content of 148 high-grade soft tissue sarcomas of the extremities and trunk was determined by flow cytometry, using tumor material from paraffin-embedded tissue. The patients were part of a prospective randomized clinical trial on the efficacy of adjuvant single-agent chemotherapy with doxorubicin. Chemotherapy did not improve the metastasis-free survival (MFS). After a median follow-up time of 48 months (range, 2 to 97), a multivariate analysis of prognostic factors for developing metastatic disease was performed. DNA aneuploidy was found to be an independent prognostic risk factor in addition to histologic malignancy grade IV, intratumoral vascular invasion, tumor size over 10 cm, and male sex. Patients with none or one risk factor had a 5-year MFS of 79%, with two risk factors 65%, with three risk factors 43%, and with four and five risk factors 0%. About one half (78 of 148) of the patients with three factors or less belonged to a group with a MFS over 60%. The combination of different risk factors, including DNA aneuploidy, seems to be a useful prognostic model for soft tissue sarcomas, which could be of value to select high-risk patients for further trials with adjunctive therapy.

scholarly journals Progress in the Systemic Treatment of Advanced Soft-Tissue Sarcomas

1998 ◽  
Vol 5 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Scott H. Okuno ◽  
John H. Edmonson
Keyword(s):  
Clinical Trials ◽  
Soft Tissue ◽  
Systemic Treatment ◽  
Soft Tissue Sarcomas ◽  
Multimodality Treatment ◽  
Clinical Situation ◽  
Controlled Clinical Trials ◽  
Systemic Treatments ◽  
Review Current ◽  
Systemic Therapies

Background: Despite the plethora of chemotherapeutic remedies for advanced soft-tissue sarcomas, little evidence has developed to indicate that these efforts have been curative. No controlled comparison has yet proven that patients receiving multidrug regimens survive longer than those receiving doxorubicin alone. Methods: The authors review current systemic treatments and then discuss some investigational efforts now in progress. Also, they seek to demonstrate how the therapies currently available can be integrated with surgery and radiation therapy to accomplish more than might be anticipated from chemotherapy alone. Results: While working to develop better systemic therapies for advanced soft-tissue sarcomas, the integrated use of our best chemotherapy regimens in combination with selected surgical and radiotherapy efforts may provide patients with the best available therapy. Some recent observations involving the use of molgramostim plus chemotherapy have been intriguing. Conclusions: Progress in the systemic treatment of advanced soft-tissue sarcomas may be gradual, but it is real. Our daily challenge is to be certain that we offer each patient the best available multimodality treatment applicable to his or her clinical situation. Molgramostim should be made available for further study with chemotherapy in controlled clinical trials.

Phase II Study of Doxorubicin and Bevacizumab for Patients With Metastatic Soft-Tissue Sarcomas

2005 ◽  
Vol 23 (28) ◽  
pp. 7135-7142 ◽  
Author(s):  
David R. D'Adamo ◽  
Sibyl E. Anderson ◽  
Karen Albritton ◽  
Jennifer Yamada ◽  
Elyn Riedel ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Stable Disease ◽  
Cardiac Toxicity ◽  
Single Agent ◽  
Soft Tissue Sarcomas ◽  
Close Monitoring ◽  
Future Studies ◽  
Metastatic Soft Tissue Sarcoma ◽  
Grade 3 ◽  
Line Of Therapy

Purpose To evaluate the antitumor activity and tolerability of bevacizumab and doxorubicin in patients with metastatic soft-tissue sarcoma (STS). Patients and Methods Patients may have had up to one nonanthracycline line of therapy. Seventeen patients with metastatic STS were treated with doxorubicin at 75 mg/m2 intravenous (IV) push followed by bevacizumab 15 mg/kg IV every 3 weeks. Dexrazoxane was started for total doxorubicin dose exceeding 300 mg/m2. Results A total of 85 cycles of doxorubicin/bevacizumab were administered, median four cycles (range, one to 11), with three patients receiving one to four cycles of bevacizumab maintenance after reaching 600 mg/m2 doxorubicin. All 17 patients were assessable for response. Two partial responses (12%, 95% CI = 1% to 36%) were observed, lasting seven and 12 cycles of therapy. Eleven patients (65%) had stable disease for four cycles or more. Six patients developed cardiac toxicity grade 2 or greater, with four patients grade 2 (cumulative doxorubicin 75, 150, 300, 300 mg/m2, respectively), one grade 3 (total doxorubicin 591 mg/m2), and one grade 4 (total doxorubicin 420 mg/m2). One patient with extensive lung disease died of recurrent bilateral pneumothoraces, possibly treatment-related. Conclusion The 12% response rate for these patients was no greater than that observed for single-agent doxorubicin. However, the 65% of patients with stable disease lasting four cycles or longer suggests further study is warranted in STSs. The observed cardiac toxicity, despite close monitoring and standard use of dexrazoxane, obliges a change in the dose and/or schedule in future studies of this combination.

scholarly journals Soft Tissue Sarcoma Guidelines

2007 ◽  
Vol 5 (4) ◽  
pp. 364 ◽  
Author(s):  
_ _
Keyword(s):  
United States ◽  
Soft Tissue ◽  
Mortality Rate ◽  
Soft Tissue Sarcoma ◽  
Single Agent ◽  
Soft Tissue Sarcomas ◽  
The United States ◽  
Desmoid Tumors ◽  
Recent Version ◽  
Overall Mortality

Soft tissue sarcomas are the most frequent sarcomas; the annual incidence for 2007 in the United States is estimated at about 9220 cases, with an overall mortality rate of approximately 3560 cases per year. Important updates for the 2007 version of the guidelines include the addition of epirubicin (single agent) and the combination of epirubicin, ifosfamide, and mesna as generally accepted systemic therapy. Imatinib was added as an option for desmoid tumors. For the most recent version of the guidelines, please visit NCCN.org

A randomized phase II trial of cabozantinib combined with PD-1 and CTLA-4 inhibition in metastatic soft tissue sarcoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS11583-TPS11583
Author(s):  
Vanessa Anne Eulo ◽  
Breelyn A. Wilky ◽  
Jingqin Luo ◽  
Angela C. Hirbe ◽  
Mia C. Weiss ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Soft Tissue ◽  
Phase Ii ◽  
Immune Checkpoint ◽  
Response Rate ◽  
Single Agent ◽  
Objective Response ◽  
Soft Tissue Sarcomas ◽  
Randomized Phase Ii ◽  
Metastatic Setting

TPS11583 Background: Soft tissue sarcomas (STS) are rare malignancies with poor prognosis in the metastatic setting. Current standard therapy includes anthracycline based chemotherapy. Cabozantinib is a multikinase inhibitor that has demonstrated efficacy in solid tumors such as renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC). A phase II study of cabozantinib in advanced STS is underway. Cabozantinib in combination with immune checkpoint blockade has shown clinical benefit in several tumor types including HCC, RCC, non-small cell lung cancer, and urothelial carcinoma. Since cabozantinib may alter PD-1 expression in regulatory T-cells and promote an immune permissive environment, we hypothesize that combining cabozantinib with immune checkpoint inhibition is a therapeutic strategy that will be more effective than cabozantinib alone. Additionally, the design of the trial will allow assessment of whether pretreatment with cabozantinib will enhance the efficacy of nivolumab and ipilimumab alone. Methods: This is an open label, multicenter, randomized phase II clinical trial of cabozantinib (60mg orally daily as a single agent, 40mg in combination) with or without combination Ipilimumab (ipi, 1mg/kg IV every 3 weeks for 4 doses) and Nivolumab (nivo, 3mg/kg IV every 3 weeks for four doses, then 480mg IV every 4 weeks) in patients (pts) with unresectable or metastatic STS refractory to up to two lines of chemotherapy. 105 pts with non-translocation driven sarcomas will be enrolled at three US sites and randomized 2:1 to the combination group. Pts will be stratified by prior pazopanib use and balanced for histologies. Patients who progress on arm A will cross over to combination therapy (arm B). The primary efficacy endpoint is objective response rate (ORR) by RECIST 1.1. 35 patients in Cohort A (cabozantinib alone) and 70 patients in Cohort B (cabozantinib plus ipi/nivo) will be required to detect an increase of the ORR from 10% in cohort A to 30% in cohort B with 81% power with a one-sided alpha level of 10%. Key eligibility criteria include: at least 18 years of age, ECOG performance status of 0 or 1, ≤2 prior lines of therapy and measurable disease. Exclusion criteria include: translocation-driven sarcoma except alveolar soft part sarcoma (ASPS), prior immunotherapy, and chronic use of corticosteroids or other immunosuppression. Secondary endpoints are safety, overall and progression free survival, disease control rate, and response rate to ipilimumab and nivolumab after cabozantinib pretreatment. Mandatory tumor biopsies pre-treatment and at 6 weeks will be obtained. Peripheral blood will be collected for circulating immune phenotyping. Enrollment will occur at 3 participating institutions and is expected to be completed in 2022. Clinical trial information: NCT04551430.

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