Phase II and Pharmacokinetic Study of Ecteinascidin 743 in Patients With Progressive Sarcomas of Soft Tissues Refractory to Chemotherapy

2004 ◽  
Vol 22 (8) ◽  
pp. 1480-1490 ◽  
Author(s):  
R. Garcia-Carbonero ◽  
J.G. Supko ◽  
J. Manola ◽  
M.V. Seiden ◽  
D. Harmon ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissues ◽  
Survival Rates ◽  
Soft Tissue Sarcomas ◽  
Complete Response ◽  
Pharmacokinetic Studies ◽  
High Survival ◽  
Previously Treated ◽  
Ecteinascidin 743 ◽  
Grade 3

Purpose To assess the efficacy of the marine-derived alkaloid ecteinascidin 743 (ET-743) in patients with soft tissue sarcomas that progressed despite prior conventional chemotherapy and to characterize the pharmacokinetic profiles of ET-743 in this patient population. Patients and Methods Thirty-six previously treated soft tissue sarcoma patients from three institutions received ET-743 as a 24-hour continuous intravenous (IV) infusion at a dose of 1,500 μg/m2 every 3 weeks. Pharmacokinetic studies were also performed. Patients were restaged every two cycles for response by objective criteria. Results Objective responses were observed in three patients, with one complete response and two partial responses, for an overall response rate of 8% (95% CI, 2% to 23%). Responses were durable for up to 20 months. Two minor responses (43% and 47% tumor reduction) were observed, for an overall clinical benefit rate of 14%. The predominant toxicities were neutropenia and self-limited transaminitis of grade 3 to 4 severity in 34% and 26% of patients, respectively. The estimated 1-year time to progression and overall survival rates were 9% (95% CI, 3% to 27%) and 53% (95% CI, 39% to 73%), respectively. The maximum observed plasma concentration and total plasma clearance of ET-743 (mean ± standard deviation), 1.04 ± 0.48 ng/mL and 35.6 ± 16.2 L/h/m2, respectively, were consistent with previously reported values from phase I studies of the drug given as a 24-hour IV infusion. Conclusion ET-743 is a promising new option for the management of several histologic subtypes of sarcoma. Durable objective responses were obtained in a subset of sarcoma patients with disease progression despite prior chemotherapy. Additionally, the relatively high survival rate noted in this series of previously treated patients further justifies development of this agent.

Ecteinascidin-743 (ET-743) for Chemotherapy-Naive Patients With Advanced Soft Tissue Sarcomas: Multicenter Phase II and Pharmacokinetic Study

2005 ◽  
Vol 23 (24) ◽  
pp. 5484-5492 ◽  
Author(s):  
R. Garcia-Carbonero ◽  
J.G. Supko ◽  
R.G. Maki ◽  
J. Manola ◽  
D.P. Ryan ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Response Rate ◽  
Survival Rates ◽  
Soft Tissue Sarcomas ◽  
Clinical Activity ◽  
First Line ◽  
Minor Response ◽  
First Line Therapy ◽  
Line Therapy ◽  
Ecteinascidin 743

Purpose To evaluate the response rate, toxicity profile, and pharmacokinetics of ecteinascidin-743 (ET-743) as first-line therapy in patients with unresectable advanced soft tissue sarcoma (STS). Patients and Methods Thirty-six patients with STS were enrolled onto the study between September 1999 and August 2000. Patients were treated with 1.5 mg/m2 of ET-743 given as a 24-hour continuous intravenous (IV) infusion every 21 days. Pharmacokinetic sampling was performed in 23 patients. Results One complete and five partial responses were achieved in 35 assessable patients for an overall response rate of 17.1% (95% CI, 6.6% to 33.6%). In addition, one patient had a minor response, leading to an overall clinical benefit of 20%. Neutropenia and transaminitis were the main grade 3 to 4 toxicities, which occurred in 33% and 36% of the patients. The estimated 1-year progression-free and overall survival rates were 21% (95% CI, 11% to 41%) and 72% (95% CI, 59% to 88%), respectively. Total body clearance (L/h) was not significantly correlated with body-surface area (r = −0.28; P = .21). Mild hepatic impairment or the extent of prior cytotoxic therapy does not seem to contribute significantly to the high interpatient variability (49%) in the clearance of this drug. Severity of treatment-related toxicity was not correlated with pharmacokinetic variables. Conclusion ET-743 demonstrates clinical activity as first-line therapy against STS with acceptable toxicity. Additional studies to establish empirical dosing guidelines may be necessary to improve the safety of the drug in patients with varying degrees of hepatic dysfunction and definitively establish the role of ET-743 for patients with these malignancies.

LOCAL RECURRENCES AFTER THE TREATMENT OF SOFT TISSUE MALIGNANT FIBROUS HISTIOCYTOMA (UNCLASSIFIEDPLEOMORPHIC SARCOMA) OF THE LIMBS

2019 ◽  
Vol 72 (8) ◽  
pp. 1523-1526
Author(s):  
Oleksandr O. Lytvynenko ◽  
Volodymyr F. Konovalenko ◽  
Anton Yu. Ryzhov
Keyword(s):  
Soft Tissue ◽  
Malignant Fibrous Histiocytoma ◽  
Fibrous Histiocytoma ◽  
Survival Rates ◽  
Soft Tissue Sarcomas ◽  
Primary Treatment ◽  
Radical Excision ◽  
Local Recurrences ◽  
Results Of Treatment

Introduction: The treatment of patients with malignant fibrous histiocytoma as well as other soft tissue sarcomas is not sufficiently effective up to date, and has largely changed and reflects the alterations, occurred in oncology as a whole. The number of amputation decreased over the last 10-15 years. Some researchers associate the improvement of treatment outcomes with the development of combined and complex methods. The aim of the study is an improvement of the results of treatment of patients with soft tissue malignant histiocytoma on the basis of determination of factors, influencing local recurrence development. Materials and methods: The basis of our study was a comprehensive analysis of examination and treatment results of 130 patients with MFH of the soft tissue of limbs, of them in 84 patients (64.6%) the recurrences developed. The group included 45 (53.6%) males and 39 (46.4%) females. The major part of patients – 82.1% (60 patients) were older than 40 years. Results and conclusions: The number of recurrences after the treatment in general surgical facilities is 86.9%, whereas in the patients after the treatment in the specialized oncological facilities this figure is twice lower (40%). The characteristic of the medical facility where the patient receives his/her primary treatment largely affects the development of local recurrences, patients’ quality of life and overall survival rates. The surgical method remains the leading modality in the treatment of MFH of ST. Wide and radical excision of tumors in the specialized oncological facilities allows achieving better survival outcomes of the patients.

scholarly journals Stereotactic Body Radiotherapy for Metastatic and Recurrent Soft Tissue Sarcoma

2020 ◽  
Author(s):  
Xiaoyao Feng ◽  
Jing Li ◽  
Aomei Li ◽  
Han Zhou ◽  
Xixu Zhu ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Hematogenous Metastasis ◽  
Invasive Growth ◽  
Free Survival ◽  
Grade 3 ◽  
Clinical Transformation

Abstract BackgroundSoft tissue sarcoma（STS） is a malignant tumor of highly heterogeneous mesenchymal origin. STS has a biologic pattern and clinical transformation with localized invasive growth and susceptibility to hematogenous metastasis. Metastatic and recurrent soft tissue sarcoma may be treated by local therapeutic options, including surgery and radiation therapy. This study evaluated the safety and efficacy of SBRT for metastatic and recurrent soft tissue sarcoma.MethodsWe performed a retrospective analysis of 37 STS patients with 58 lesions treated with SBRT from 2009-2019 at our institution. We analyze the local control (LC), overall survival (OS), progression free survival (PFS) and toxicity rates of the patients.ResultThe median follow-up was 20 months（range 2 to 120 months）. One and two year LC rates were 75.3% and 55.2% [95% confidence interval (CI) 20–25 months]. Median OS was 24 months and the survival rates were 66.6%, 45% and 26.6% at 1, 2 and 3-year after SBRT. Median PFS were 11months (95% CI 8–18 months). No acute or chronic grade ≥ 3 toxicity was observed.ConclusionsIn patients with metastatic and recurrent STS, LC, OS and PFS were higher than expected. SBRT should be a proper treatment option for STS.

Sarcomas of Soft Tissue and Bone

2011 ◽  
Author(s):  
Adam Lerner ◽  
Huihong Xu ◽  
Karen H Antman
Keyword(s):  
Soft Tissue ◽  
Meta Analysis ◽  
Survival Rates ◽  
Fibrous Tissue ◽  
Soft Tissue Sarcomas ◽  
Kaposi Sarcoma ◽  
Uterine Leiomyosarcoma ◽  
Increased Risk ◽  
Bone Sarcomas ◽  
Epidemiologic Features

Sarcomas originate from bone or soft tissue. The most common bone sarcomas are osteosarcomas, Ewing sarcomas, and chondrosarcomas. Soft tissue sarcomas develop in fibrous tissue, fat, muscle, blood vessels, and nerves. Historically, soft tissue sarcomas of the trunk and extremities were reported separately from those of visceral organs (e.g., gastrointestinal and gynecologic sarcomas). This chapter discusses the classification, epidemiology, diagnosis, staging, and treatment of sarcomas of bone and cartilage, and classic soft tissue sarcomas. Management of Kaposi sarcoma, gastrointestinal stromal tumors (GISTs), mesothelioma, and rhabdomyosarcoma is also described. Figures include images of patients with osteosarcoma, liposarcoma, uterine leiomyosarcoma, GIST, and osteosarcoma in a patient with Paget disease of bone. Tables list epidemiologic features of sarcomas, a summary of sarcomas by histology, familial syndromes associated with increased risk of sarcoma, survival rates in sarcoma patients, staging of soft tissue sarcomas, and results of a meta-analysis of doxorubicin-based adjuvant chemotherapy for localized resectable soft tissue sarcoma. This chapter contains 126 references.

Randomized Phase III Study Comparing Conventional-Dose Doxorubicin Plus Ifosfamide Versus High-Dose Doxorubicin Plus Ifosfamide Plus Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor in Advanced Soft Tissue Sarcomas: A Trial of the European Organization for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group

2000 ◽  
Vol 18 (14) ◽  
pp. 2676-2684 ◽  
Author(s):  
A. Le Cesne ◽  
I. Judson ◽  
D. Crowther ◽  
S. Rodenhuis ◽  
H.J. Keizer ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Dose Regimen ◽  
Standard Dose ◽  
Soft Tissue Sarcomas ◽  
Dose Intensity ◽  
High Dose ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Grade 3 ◽  
Stimulating Factor

PURPOSE: This randomized multicenter study was designed to compare the activity of a high-dose doxorubicin-containing chemotherapy regimen with a conventional standard-dose regimen in adult patients with advanced soft tissue sarcomas (ASTS). PATIENTS AND METHODS: Between 1992 and 1995, 314 patients were randomized to receive a standard-dose regimen (arm A), containing doxorubicin (50 mg/m2 on day 1) and ifosfamide (5 g/m2 on day 1), or an intensified regimen (arm B), combining doxorubicin (75 mg/m2 on day 1), the same ifosfamide dose, and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; sargramostim, 250 μg/m2 on days 3 to 16); all courses were repeated every 3 weeks. RESULTS: The median age of the 294 eligible patients was 50 years. They received a median of five chemotherapy cycles. The median dose and relative doxorubicin dose-intensity achieved were 245 mg and 97% in arm A and 360 mg and 99% in arm B, respectively. Thirty-eight percent and 23% of patients presented with leiomyosarcomas and liver metastases, respectively. Objective responses were observed in 31 (21%) of 147 assessable patients in arm A and in 31 (23.3%) of 133 in arm B (P = .65). No change was observed in 41.6% and 46.2% of patients in arm A and B, respectively. Progression-free survival (PFS) was significantly longer in the intensive arm (P = .03). The median duration of the time to progression was 19 weeks in the conventional arm and 29 weeks in the intensified arm. There was no difference in overall survival (P = .98) between the two therapeutic arms. Toxicities were manageable in both arms. A grade 3/4 neutropenia and infection occurred in 92% and 4.6% of patients in arm A, respectively, and in 90% and 16.6% in arm B, respectively. Grade 3/4 thrombocytopenia was more frequent in arm B. CONCLUSION: The use of rhGM-CSF allowed safe escalation of chemotherapy doses. Despite a 50% increase of the doxorubicin dose-intensity, the high-dose regimen failed to demonstrate any impact on survival in patients with ASTS. The low complete response rate, the high incidence of leiomyosarcomas, and liver metastases may in part explain these results. However, the lengthening of the PFS in the intensive arm, because of the quality of stable disease and inappropriate tumor evaluation policies that potentially lead to an underestimation of antitumor activity, does not definitively refute the use of a high-dose chemotherapy regimen in selected patients with ASTS.

Treatment-Induced Pathologic Necrosis: A Predictor of Local Recurrence and Survival in Patients Receiving Neoadjuvant Therapy for High-Grade Extremity Soft Tissue Sarcomas

2001 ◽  
Vol 19 (13) ◽  
pp. 3203-3209 ◽  
Author(s):  
Fritz C. Eilber ◽  
Gerald Rosen ◽  
Jeffery Eckardt ◽  
Charles Forscher ◽  
Scott D. Nelson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Local Recurrence ◽  
Neoadjuvant Therapy ◽  
Independent Predictor ◽  
Survival Rates ◽  
Soft Tissue Sarcomas ◽  
High Grade ◽  
Recurrence Rates ◽  
Pathologic Assessment

PURPOSE: To determine whether treatment-induced pathologic necrosis correlates with local recurrence and overall survival in patients who receive neoadjuvant therapy for high-grade extremity soft tissue sarcomas. PATIENTS AND METHODS: Four hundred ninety-six patients with intermediate- to high-grade extremity soft tissue sarcomas received protocol neoadjuvant therapy. All patients underwent surgical resection after neoadjuvant therapy and had pathologic assessment of tumor necrosis in the resected specimens. RESULTS: The 5- and 10-year local recurrence rates for patients with ≥ 95% pathologic necrosis were significantly lower (6% and 11%, respectively) than the local recurrence rates for patients with less than 95% pathologic necrosis (17% and 23%, respectively). The 5- and 10-year survival rates for the patients with ≥ 95% pathologic necrosis were significantly higher (80% and 71%, respectively) than the survival rates for the patients with less than 95% pathologic necrosis (62% and 55%, respectively). Patients with less than 95% pathologic necrosis were 2.51 times more likely to develop a local recurrence and 1.86 times more likely to die of their disease as compared with patients with ≥ 95% pathologic necrosis. The percentage of patients who achieved ≥ 95% pathologic necrosis increased to 48% with the addition of ifosfamide as compared with 13% of the patients in all the other protocols combined. CONCLUSION: Treatment-induced pathologic necrosis is an independent predictor of both local recurrence and overall survival in patients who receive neoadjuvant therapy for high-grade extremity soft tissue sarcomas. A complete pathologic response (≥ 95% pathologic necrosis) correlated with a significantly lower rate of local recurrence and improved overall survival.

scholarly journals Prospective evaluation of multitarget treatment of pediatric patients with helical intensity-modulated radiotherapy

2020 ◽  
Vol 196 (12) ◽  
pp. 1103-1115
Author(s):  
Maria-Elena A. Salfelder ◽  
Kerstin A. Kessel ◽  
Uwe Thiel ◽  
Stefan Burdach ◽  
Severin Kampfer ◽  
...  
Keyword(s):  
Survival Rate ◽  
Side Effects ◽  
Survival Rates ◽  
Young Patients ◽  
Intensity Modulated Radiotherapy ◽  
High Survival ◽  
Single Target ◽  
Number Of Patients ◽  
Grade 3

Abstract Background and purpose Radiotherapy (RT) is persistently gaining significance in the treatment of pediatric tumors. However, individual features of a growing body and multifocal stages complicate this approach. Tomotherapy offers advantages in the treatment of anatomically complex tumors with low risks of side effects. Here we report on toxicity incidence and outcome of tomotherapy with a focus on multitarget RT (mtRT). Materials and methods From 2008 to 2017, 38 children diagnosed with sarcoma were treated with tomotherapy. The median age was 15 years (6–19 years). Toxicity was graded according to the Common Terminology Criteria for Adverse Events v.4.03 and classified into symptoms during RT, acutely (0–6 months) and late (>6 months) after RT, and long-term sideeffects (>24 months). Results The main histologies were Ewing sarcoma (n = 23 [61%]) and alveolar rhabdomyosarcoma (n = 5 [13%]). RT was performed with a median total dose of 54 Gy (40.5–66.0 Gy) and a single dose of 2 Gy (1.80–2.27 Gy). Twenty patients (53%) received mtRT. Median follow-up was 29.7 months (95% confidence interval 15.3–48.2 months) with a 5-year survival of 55.2% (±9.5%). The 5‑year survival rate of patients with mtRT (n = 20) was 37.1 ± 13.2%, while patients who received single-target RT (n = 18) had a 5-year survival rate of 75 ± 10.8%. Severe toxicities (grade 3 and 4) emerged in 14 patients (70%) with mtRT and 7 patients (39%) with single-target RT. Two non-hematological grade 4 toxicities occurred during RT: one mucositis and one radiodermatitis. After mtRT 5 patients had grade 3 toxicities acute and after single-target RT 4 patients. One patient had acute non-hematological grade 4 toxicities (gastritis, pericarditis, and pericardial effusion) after mtRT. Severe late effects of RT occurred in 2 patients after mtRT and in none of the single-target RT patients. No severe long-term side effects appeared. Conclusion Our results showed acceptable levels of acute and late toxicities, considering the highly advanced diseases and multimodal treatment. Hence, tomotherapy is a feasible treatment method for young patients with anatomically complex tumors or multiple targets. Especially mtRT is a promising and innovative treatment approach for pediatric sarcomas, delivering unexpectedly high survival rates for patients with multifocal Ewing sarcomas in this study, whereby the limited number of patients should invariably be considered in the interpretation.

Extended ray resection for sarcoma of the hand: long-term survival and functional results

2019 ◽  
Vol 45 (2) ◽  
pp. 160-166 ◽  
Author(s):  
Farhad Farzaliyev ◽  
Hans-Ulrich Steinau ◽  
Halil-Ibrahim Karadag ◽  
Alexander Touma ◽  
Lars Erik Podleska
Keyword(s):  
Soft Tissue ◽  
Survival Rates ◽  
Soft Tissue Sarcomas ◽  
Functional Results ◽  
Contralateral Side ◽  
Level Of Evidence ◽  
Term Survival ◽  
Kaplan Meier

In this retrospective study, we analysed the long-term oncological and functional results after extended ray resection for sarcoma of the hand. Recurrence-free and overall survivals were calculated using the Kaplan–Meier method. The function of the operated hand was assessed with the Michigan Hand Questionnaire and compared with the contralateral side. Extended ray resection was performed in 25 out of 168 consecutive patients with soft-tissue and bony sarcomas of the hand. The overall 5- and 10-year, disease-specific survival rates were 86% and 81%, respectively. Local recurrences were observed in two patients. The Michigan Hand Questionnaire score for the affected hand at follow-up in nine patients was 82 points versus 95 for the healthy contralateral hands. We conclude that extended ray resection of osseous sarcomas breaking through the bone into the soft tissue or for soft tissue sarcomas invading bone is a preferable alternative to hand ablation when excision can be achieved with tumour-free margins. Level of evidence: III

scholarly journals Oral Health and Molecular Aspects of Malignant Fibrous Histiocytoma Patients: A Systematic Review of the Literature

2020 ◽  
Vol 17 (4) ◽  
pp. 1426
Author(s):  
Khrystyna Zhurakivska ◽  
Giuseppe Troiano ◽  
Marco Montella ◽  
Lorenzo Lo Muzio ◽  
Luca Fiorillo ◽  
...  
Keyword(s):  
Systematic Review ◽  
Soft Tissue ◽  
Malignant Fibrous Histiocytoma ◽  
Soft Tissues ◽  
Fibrous Histiocytoma ◽  
Case Reports ◽  
Soft Tissue Sarcomas ◽  
Clinical Aspects ◽  
Risk Of Death ◽  
Short Period

Malignant fibrous histiocytoma is one of the most common soft tissue sarcomas in adults. It occurs only occasionally in oral soft tissues, and knowledge about its characteristics is based on a limited number of cases reported in the literature. Malignant fibrous histiocytoma belongs to the group of soft tissue sarcomas and makes up less than 10% of soft tissue sarcomas. For therapeutic purposes, complete exeresis of the lesion (macroscopic and microscopic) is performed because they have frequent recurrences. As for complementary therapy in addition to surgery, neither radiotherapy nor chemotherapy have been shown to reduce the risk of death related to the disease. Often patients complain of a swelling that grows in a short period of time. It is quite common for patients to report trauma in the area, which is not the cause, but rather the event that allows diagnosis. The mass usually does not cause pain unless it compresses an adjacent nerve structure. The aim of this study is to systematically review the scientific literature in order to identify the most recent studies concerning malignant fibrous histiocytomas localized in oral soft tissues and report their main data. The main outcomes of this study concern the immunohistochemical, molecular, and clinical aspects of this pathology. A systematic review of articles in the electronic databases pubmed, Scopus, and Web of Science was performed. After the selection process, 11 studies met the inclusion criteria and were included in the review. The mean age of the patients was 50.8 years old. The lesions affected various parts of the oral cavity, showing predominantly storiform–pleomorphic patterns. All cases except one were treated with surgical resection and radiation therapy. Although some data emerged from this review, they remain limited to a few case reports. Further studies are necessary in order to standardize the approach to patients affected by oral malignant fibrous histiocytoma (MFH).

scholarly journals A Phase II Nonrandomised Open-Label Study of Liposomal Daunorubicin (DaunoXome) in Advanced Soft Tissue Sarcoma

Sarcoma ◽  
2006 ◽  
Vol 2006 ◽  
pp. 1-5 ◽  
Author(s):  
Anne McTiernan ◽  
Jeremy Whelan ◽  
Michael Leahy ◽  
Penella J. Woll ◽  
Ian Judson
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Significant Activity ◽  
Open Label ◽  
Advanced Soft Tissue Sarcoma ◽  
Liposomal Daunorubicin ◽  
Open Label Study ◽  
Previously Treated ◽  
Grade 3 ◽  
Free Rate

Thirty four patients with advanced soft tissue sarcoma not previously treated with an anthracycline were treated with DaunoXome 100mg/m2 every 3 weeks. Thirty-three patients were evaluable for toxicity. Grade 3-4 neutropenia was seen in 20 patients (60.6%), complicated by febrile neutropenia in 2 (6.1%). Other grade 3 toxicities were rare. Among 32 patients assessable for response, one patient had a partial response, giving a response rate of 3.13% (95% confidence interval, 0.08–16.22%). Seven patients (21.9%) had stable disease, and 24 patients (75.0%) had disease progression. The median time to progression for all patients was 42 days (95% CI, 39–49) and the progression-free rate at 3 months was 12.5%. In conclusion, DaunoXome at this dose and schedule is well tolerated in patients with advanced soft tissue sarcoma, but is not associated with significant activity. Further studies at this dose and schedule cannot be recommended in this disease.

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