Phase Ib study of decitabine in combination with gemcitabine in treatment of advanced soft tissue and bone sarcomas.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 11550-11550
Author(s):  
Varun Monga ◽  
Rebecca Dodd ◽  
Amanda Scherer ◽  
Wade Robert Gutierrez ◽  
Munir Tanas ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcomas ◽  
Bone Sarcoma ◽  
Disease Assessment ◽  
Fixed Dose ◽  
Weekly Schedule ◽  
Hypomethylating Agent ◽  
Dose Infusion ◽  
Bone Sarcomas ◽  
Grade 3

11550 Background: Sarcomas are a heterogeneous group of tumors and are associated with high rates of metastases leading to poor prognosis. Numerous epigenetic changes including hypermethylation have been identified in several sarcoma subtypes. Restoration of normal methylation patterns using DNA hypomethylating agent when combined with chemotherapy has shown to slow tumor growth in preclinical studies. Low continuous dosing of hypomethylating agent has epigenetic modulating effect with less toxicity. We conducted a Phase 1b study evaluating safety & tolerability and identifying the recommended phase 2 dose (RP2D) of subcutaneous (SQ) decitabine (DEC) given with fixed dose infusion gemcitabine (GEM) in patients with advanced soft tissue sarcomas (STS) and bone sarcomas. Methods: Eligible patients at least age 18 yrs with metastatic histologically confirmed STS or bone sarcoma after progression on one line or if refused adriamycin for STS were included. Prior GEM use was permitted. A modified 3+3 dose escalation design was used exploring two dose cohorts of DEC, 0.1 and 0.2 mg/kg SQ administered on a twice weekly schedule for three weeks and GEM given as 900 mg/m2, IV over 90 min on days 1, 8 & 15 of a 28-day cycle. Treatment was continued until disease progression or unacceptable toxicity. Dose limiting toxicity (DLT) was defined as any drug related non-hematological grade 3 or 4 toxicity per CTCAE v4.0. Disease assessment was performed every 8 weeks using RECIST v1.1. Results: 31 patients (25 STS & 6 bone sarcomas) were enrolled of which 7 were non-evaluable. There were 12 evaluable patients in each dosing cohort. Of the total 744 adverse events (AE) 17.2% were grade 3/4 and most were neutropenia without neutropenic fever. 45.7% AEs were possibly (44.6%) or probably (1.1%) attributed to DEC use. The toxicities were not significantly different between DEC doses. No DLTs were observed. One patient died due to progressive disease. Conclusions: Combination of fixed dose infusion GEM with low dose subcutaneous DEC is moderately toxic. Most toxicities were hematological. While there were few responses, the RP2D of DEC selected was 0.1 mg/kg as it showed prolonged disease stabilization. Clinical trial information: NCT02959164 . [Table: see text]

scholarly journals Imaging of Bone Sarcomas and Soft-Tissue Sarcomas

2021 ◽  
Author(s):  
Jasminka Igrec ◽  
Michael H. Fuchsjäger
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcomas ◽  
Bone Cancer ◽  
Bone Sarcoma ◽  
Daily Practice ◽  
Imaging Evaluation ◽  
Key Points ◽  
Bone Sarcomas ◽  
Publication Period ◽  
Ct And Mri

Background In the diagnosis of bone and soft-tissue sarcomas, the continuous advancement of various imaging modalities has improved the detection of small lesions, surgical planning, assessment of chemotherapeutic effects, and, importantly, guidance for surgery or biopsy. Method This review was composed based on a PubMed literature search for the terms “bone sarcoma,” “bone cancer” and “soft tissue sarcoma,” “imaging,” “magnetic resonance imaging”, “computed tomography”, “ultrasound”, “radiography”, and “radiomics” covering the publication period 2005–2020. Results and Conclusion As discussed in this review, radiography, ultrasound, CT, and MRI all play key roles in the imaging evaluation of bone and soft-tissue sarcomas. In daily practice, advanced MRI techniques complement standard MRI but remain underused, as they are considered time-consuming, technically challenging, and not reliable enough to replace biopsy and histology. PET/MRI and radiomics have shown promise regarding the imaging of sarcomas in the future. Key Points:  Citation Format

Bone cancer

2007 ◽  
pp. 295-308
Keyword(s):  
Soft Tissue ◽  
Bone Disease ◽  
Soft Tissue Sarcomas ◽  
Bone Cancer ◽  
Bone Sarcoma ◽  
Metastatic Bone Disease ◽  
Childhood Cancers ◽  
Bone Sarcomas ◽  
The Uk ◽  
Surgical Treatments

Bone sarcomas 296 Soft tissue sarcomas 300 Surgical treatments 302 Metastatic bone disease (MBD) 306 Bone sarcomas are extremely rare, with less than 550 new cases per annum in the UK. They account for only 0.2% of all new cancers, but 5% of childhood cancers. The main types of bone sarcoma/tumour are:...

scholarly journals Oncoepidemiological situation of sarcomas in Kazakhstan

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
Z h U Pyssanova ◽  
G A Serikbaev ◽  
D R Kaydarova ◽  
D A Tuleuova ◽  
A S Shinbolatova ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Soft Tissue ◽  
Cancer Detection ◽  
Malignant Tumor ◽  
Soft Tissues ◽  
Malignant Tumors ◽  
Soft Tissue Sarcomas ◽  
Bone Sarcoma ◽  
The Past ◽  
Bone Sarcomas

Abstract Background Sarcoma is a malignant tumor of soft tissues and bones. They make up 1% of all malignant tumors in adults and 15% in children. More common in men 1.1: 1. By age: 20.7% - up to 40 years old, 27.6% - 40-60 years old and 51.7% over 60 years old. In 2018, in the Kazakhstan, malignant tumor of connective and soft tissues of 444 (1.4%) cases was registered and ranks 19th in the structure of cancer, bones and articular cartilage 188 (0.6%), takes 22nd place. Of these, with sore cases, bone sarcomas were recorded - 12.7%, soft tissues - 9.5%. The mortality rate from soft tissue sarcoma is -177 (1.2%) people, bone sarcoma - 85 (0.6%) people. Five-year survival of patients from soft tissue sarcomas is 53.8%, from bone sarcomas - 67.3%. Methods from 2015 to 2019, 1,068 patients with malignant tumor of bones and articular cartilage, 963 patients with malignant tumor of connective and soft tissues addmited to KazNIIOiR. Of these, 225 patients underwent organ-sparing surgeries - endoprosthesis replacement of limbs. Results In Kazakhstan over the past 5 years there has been an increase in the incidence of sarcomas of bones and soft tissues. Conclusions in comparison with previous years, there is an increase in the incidence of malignant tumor of bones and articular cartilage, connective and soft tissues, and an increase in mortality from tumor of bones and articular cartilage in men by 16.7%, in women by 50%. Late reversal of patients at the IV stage and a high proportion posthumously recorded in patients with maliganan tumors. Key messages Purpose: Assessment of the epidemiological situation and incidence of sarcomas of the bones and soft tissues in Kazakhstan. Out of 25 localizations of cancer, detection is worsened during professional examinations in 10 localizations, of which bones and articular cartilage, connective and other soft tissues.

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.

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.

Paclitaxel in patients (pts) with advanced angiosarcomas

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10033-10033 ◽  
Author(s):  
M. Schlemmer ◽  
P. Reichardt ◽  
J. Verweij ◽  
J. T. Hartmann ◽  
I. Judson ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Active Agent ◽  
Soft Tissue Sarcomas ◽  
Bone Sarcoma ◽  
Tumor Control ◽  
Cancer History ◽  
Heterogenous Group ◽  
The Face ◽  
Prospective Phase ◽  
Collection Form

10033 Background: Angiosarcomas represent a heterogenous group of rare sarcomas with specific clinical behaviour and risk factors. Paclitaxel has been suggested to induce tumor control in a proportion of pts with angiosarcoma while being inactive in other soft tissue sarcomas subtypes. The objective of this retrospective study was to investigate the antitumor activity of this compound in a larger series and a multicenter setting. Patients and Methods: Data from pts with angiosarcoma treated with paclitaxel in centers of the EORTC Soft Tissue and Bone Sarcoma Group were collected using a standardized data collection form. Results: Data from 32 pts were collected from 10 centers. There were 17 males and 15 females with a median age of 60.4 years (range 24–91). Eight pts (25%) had angiosarcomas of the face and scalp, 24 pts (75%) at other primary sites. Ten (31 %) pts had a previous cancer history, 7 of whom had been irradiated for breast cancer. Ten (31 %) pts had received 1st line chemotherapy (ctx) and 3 pts 2nd line ctx prior to treatment with paclitaxel. All 13 (40%) pretreated pts had doxorubicin, 5 pts in combination with ifosfamide as 1st line and 3 pts ifosfamide as 2nd line ctx. 21 (66 %) pts received paclitaxel 175 mg/m2 every 3 weeks, and 11 (34 %) received 75–100 mg/m2weekly. The overall response rate (RR) was 62.5 % [including 1 CR (3%) and 19 PR (59%)]; in pts with face and scalp primary sites the RR was 75% (1CR, 5 PR), whereas pts with angiosarcoma at other sites achieved a response in 58% (14 PR). PFS was 7.6 months for all 32 pts. Conclusion: Paclitaxel was an active agent in angiosarcoma in this retrospective multicenter study, also in angiosarcoma originating at other sites than scalp and face. These results need to be confirmed in a controlled, prospective phase II study. No significant financial relationships to disclose.

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