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Clinical Cancer Research : An Official... Jul 2021To report the interim analysis of the phase II single-arm noninferiority trial, testing the upfront use of dexrazoxane with doxorubicin on progression-free survival...
PURPOSE
To report the interim analysis of the phase II single-arm noninferiority trial, testing the upfront use of dexrazoxane with doxorubicin on progression-free survival (PFS) and cardiac function in soft-tissue sarcoma (STS).
PATIENTS AND METHODS
Patients with metastatic or unresectable STS who were candidates for first-line treatment with doxorubicin were deemed eligible. An interim analysis was initiated after 33 of 65 patients were enrolled. Using the historical control of 4.6 months PFS for doxorubicin in the front-line setting, we tested whether the addition of dexrazoxane affected the efficacy of doxorubicin in STS. The study was powered so that a decrease of PFS to 3.7 months would be considered noninferior. Secondary aims included cardiac-related mortality, incidence of heart failure/cardiomyopathy, and expansion of cardiac monitoring parameters including three-dimensional echocardiography. Patients were allowed to continue on doxorubicin beyond 600 mg/m if they were deriving benefit and were not demonstrating evidence of symptomatic cardiac dysfunction.
RESULTS
At interim analysis, upfront use of dexrazoxane with doxorubicin demonstrated a PFS of 8.4 months (95% confidence interval: 5.1-11.2 months). Only 3 patients were removed from study for cardiotoxicity, all on > 600 mg/m doxorubicin. No patients required cardiac hospitalization or had new, persistent cardiac dysfunction with left ventricular ejection fraction remaining below 50%. The median administered doxorubicin dose was 450 mg/m (interquartile range, 300-750 mg/m).
CONCLUSIONS
At interim analysis, dexrazoxane did not reduce PFS in patients with STS treated with doxorubicin. Involvement of cardio-oncologists is beneficial for the monitoring and safe use of high-dose anthracyclines in STS..
Topics: Aged; Antibodies, Monoclonal; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Dexrazoxane; Disease-Free Survival; Doxorubicin; Female; Heart; Humans; Male; Middle Aged; Neoplasm Staging; Prospective Studies; Sarcoma; Soft Tissue Neoplasms
PubMed: 33766818
DOI: 10.1158/1078-0432.CCR-20-4621 -
ESMO Open 2019Phyllodes tumours of the breast are rare mesenchymal tumours with differential malignant potential. Treatment of choice is radical excision with negative margins....
Phyllodes tumours of the breast are rare mesenchymal tumours with differential malignant potential. Treatment of choice is radical excision with negative margins. Radiation therapy has shown controversial results in small series. Chemotherapy in the adjuvant setting still remains a matter of debate. Doxorubicin-based chemotherapy is recommended for breast sarcomas' first-line treatment. Herein we present two cases of breast phyllodes tumour treated with the recent combination of doxorubicin and olaratumab.
PubMed: 31321082
DOI: 10.1136/esmoopen-2018-000479 -
South Asian Journal of Cancer 2019In this decade the treatment of advanced sarcoma has seen many highs and lows in terms of successful trials and failed trials. This is possible due to great...
BACKGROUND
In this decade the treatment of advanced sarcoma has seen many highs and lows in terms of successful trials and failed trials. This is possible due to great collaborations, newer therapies and histology focused trials.
METHODS
In ASCO 2019 many sarcoma trials were presented and we chose 3 challenging clinical trials that widen our perspective on soft tissue sarcoma. We have critically analyzed the data and have discussed the implications of these trials on current practice. First trial was ANNOUNCE trial which was done to confirm the efficacy of olaratumab after its dramatic success in advanced soft tissue sarcoma in a phase 2 trial. Another trial STRASS trial, which was unique because of being first successfully conducted randomized trial addressing preoperative radiotherapy in retroperitoneal soft tissue sarcoma. Third trial was phase 2 trial SARC 028 trial exploring the role of immunotherapy in pleomorphic undifferentiated sarcoma and liposarcoma subgroup.
RESULT
ANNOUNCE trial failed to show OS benefit in olaratumab/doxorubicin arm as compared to doxorubicin/placebo arm. Based upon this FDA has revoked the approval of olaratumab leading to nihilism and disappointment amongst oncologists. In STRASS trial failed to meet the primary end point though there was a benefit in the liposarcoma subgroup in terms of abdominal recurrence free survival. There are several reasons that this trial might have failed. First, RPSs are not homogeneous population. RPSs might behave very differently as per the histopathology ranging from well differentiated LPS to leiomyosarcoma. Since the event rate in well-differentiated liposarcoma might happen late, the median follow-up of 43 months might not be sufficient. In SARC trial ORR in pleomorphic undifferentiated sarcoma (PUS) cohort was 9/40 (22.5%), while response rates in liposarcoma cohort were 4/39 (10.2%). There was poor correlation between the response and the tumor cells' PD-L1 positivity. Simultaneously, we must not take for granted the role of pembrolizumab in PUS as the previous study (PEMBROSARC) had also showed dismal outcomes with immunotherapy.
CONCLUSION
In this paper we discuss the intricacies of these trials and how they affect the rapidly changing landscape in advanced soft tissue sarcoma.
PubMed: 31807494
DOI: 10.4103/sajc.sajc_215_19 -
Implication of platelet-derived growth factor receptor alpha in prostate cancer skeletal metastasis.Chinese Journal of Cancer Sep 2011Metastasis represents by far the most feared complication of prostate carcinoma and is the main cause of death for patients. The skeleton is frequently targeted by... (Review)
Review
Metastasis represents by far the most feared complication of prostate carcinoma and is the main cause of death for patients. The skeleton is frequently targeted by disseminated cancer cells and represents the sole site of spread in more than 80% of prostate cancer cases. Compatibility between select malignant phenotypes and the microenvironment of colonized tissues is broadly recognized as the culprit for the organ-tropism of cancer cells. Here, we review our recent studies showing that the expression of platelet-derived growth factor receptor alpha (PDGFRα) supports the survival and growth of prostate cancer cells in the skeleton and that the soluble fraction of bone marrow activates PDGFRα in a ligand-independent fashion. Finally, we offer pre-clinical evidence that this receptor is a viable target for therapy.
Topics: Animals; Antibodies, Monoclonal; Bone Marrow; Bone Neoplasms; Enzyme Activation; Humans; Male; Prostatic Neoplasms; Receptor, Platelet-Derived Growth Factor alpha; Signal Transduction; Transcriptional Activation
PubMed: 21880182
DOI: 10.5732/cjc.011.10225 -
BMJ Case Reports Sep 2018Primary renal angiosarcoma is an exceedingly rare and aggressive neoplasm. Although it may occur in youth, this tumour is frequently reported in the sixth and seventh...
Primary renal angiosarcoma is an exceedingly rare and aggressive neoplasm. Although it may occur in youth, this tumour is frequently reported in the sixth and seventh decades of life. The clinical presentation is frequently varied. Pathogenesis remains largely unknown and it has overlapping features with other tumours of the kidney. Current treatment options include variable combinations of surgery, chemotherapy and radiotherapy. Reports regarding the disease prognosis and natural history are limited. In this article, we chronicle the case of a patient with primary renal angiosarcoma presenting at an advanced stage as a widely metastasised tumour. Additionally, we undertake here a brief literature review highlighting the rarity and aggressiveness of this condition, its poor prognosis, and the lack of specific management guidelines.
Topics: Aged; Antibiotics, Antineoplastic; Antibodies, Monoclonal; Biopsy, Fine-Needle; Biopsy, Needle; Doxorubicin; Hemangiosarcoma; Humans; Kidney Neoplasms; Liver Neoplasms; Male; Tomography, X-Ray Computed
PubMed: 30244222
DOI: 10.1136/bcr-2018-225484 -
Therapeutics and Clinical Risk... 2020Epithelioid hemangioendothelioma (EHE) is a rare vascular malignant tumor with indolent course. Liver transplantation for local disease is the treatment of choice. In...
Epithelioid hemangioendothelioma (EHE) is a rare vascular malignant tumor with indolent course. Liver transplantation for local disease is the treatment of choice. In the metastatic setting there is no consensus regarding the appropriate systemic treatment. We present two cases of metastatic hepatic epithelioid hemangioendothelioma (hEHE) treated with the combination of Doxorubicin and Olaratumab. Both patients showed Stable Disease (SD) as a response, after the completion of six cycles of this combination therapy.
PubMed: 32161464
DOI: 10.2147/TCRM.S220804 -
Frontiers in Oncology 2021Leiomyosarcoma is a highly malignant soft-tissue sarcoma with a poor prognosis. In recent years, treatment for leiomyosarcoma has not shown much progress. Primary...
BACKGROUND
Leiomyosarcoma is a highly malignant soft-tissue sarcoma with a poor prognosis. In recent years, treatment for leiomyosarcoma has not shown much progress. Primary intracranial leiomyosarcoma (PILMS) is a much rarer type of neoplasm, which occurs more frequently in immunocompromised patients. PILMS cases reported in the literature are scarce and treatment strategy and prognosis are still under debate. In this study, a case of PILMS secondary to the total resection of giant cell glioblastoma is reported.
CASE DESCRIPTION
A 38-year-old male was hospitalized with a three-month history of a temporal opisthotic bump. His medical history included a total resection of a tumor located in the right temporal lobe performed 4 years earlier. Pathological examination led to a diagnosis of giant cell glioblastoma, and the patient underwent postoperative chemotherapy with temozolomide for 6 weeks plus simultaneous radiotherapy with 63.66 Gary. Four years later, during regular follow-up, a preoperative MRI brain scan resulted in a well-defined signal pointing out two nodule-like features located at the right temporal lobe and subcutaneous soft tissue, respectively, and near the area where the previous giant cell glioblastoma was located. The mass was completely removed by a transtemporal approach and postoperative pathology revealed that the mass was a leiomyosarcoma. The patient underwent postoperative radiotherapy and no recurrence occurred until now.
CONCLUSIONS
To date, research on soft-tissue sarcoma, especially PILMS, has not made much progress, and a limited number of studies have provided few details on the management of PILMS. The treatment of choice for PILMS is aggressive multimodal treatment based on total tumor resection and radiotherapy. Moreover, systemic treatment with chemotherapy and targeted therapy, such as olaratumab, as well as further research still needs to be performed as many questions are left unanswered. To our knowledge, this is the first report on a case of PILMS secondary to glioblastoma, which might serve as a potential reference for clinicians and clinical studies.
PubMed: 34094927
DOI: 10.3389/fonc.2021.642683 -
Translational Lung Cancer Research Jan 2021Embryonal rhabdomyosarcoma (ERMS) is associated with a low prevalence, poor prognosis, and limited treatment efficacy. Here, we report a case of a 21-year-old male whose...
Embryonal rhabdomyosarcoma (ERMS) is associated with a low prevalence, poor prognosis, and limited treatment efficacy. Here, we report a case of a 21-year-old male whose disease relapsed in the thoracic cavity following traditional chemotherapy. The patient received eight sequential cycles of traditional chemotherapy using a combination of the cyclophosphamide + vincristine + doxorubicin hydrochloride liposome (CAV) and etoposide + ifosfamide (IE) regimens. The therapeutic effect of the combination regimen had been worked in short times. After a month, ERMS had relapsed in the whole lung after traditional chemotherapy. The treatment method was changed immediately and the patient received targeted therapy with a combination of pazopanib and olaratumab. The therapeutic effect of the combination regimen was evaluated for a complete response (CR). After two months, CT imaging revealed that most of the metastatic lesions in the lung had disappeared. This is the first case to report the use of pazopanib and olaratumab in relapsed ERMS with a curative effect resulting in a CR. Pazopanib is approved for advanced soft tissue sarcoma (STS) and renal cell cancer. Thus, combining pazopanib with targeted therapy may play an important role and provide a reference for the treatment of relapsed ERMS.
PubMed: 33569329
DOI: 10.21037/tlcr-19-644 -
Rare Tumors 2022Patient-reported outcomes (PROs), including health-related quality of life, are recommended to be routinely collected in clinical trials, but data are limited from...
BACKGROUND
Patient-reported outcomes (PROs), including health-related quality of life, are recommended to be routinely collected in clinical trials, but data are limited from trials of sarcoma patients. In this analysis, pooled PRO data are reported from patients with advanced or metastatic soft tissue sarcoma (STS) enrolled to the ANNOUNCE phase III trial of doxorubicin-based therapy.
METHODS
ANNOUNCE was a phase III trial that randomized 509 patients with STS to receive up to eight cycles of doxorubicin with olaratumab or placebo, followed by single-agent olaratumab or placebo. Dexrazoxane was allowed at any cycle of treatment. Participants completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30, which is scored 0-100), and Brief Pain Inventory Short Form Modified (mBPI-sf, scored from 0-10) at each treatment cycle. A descriptive analysis of the longitudinal data was conducted overall and by cumulative dose of doxorubicin received to inform the clinical care of patients with STS. Worsening on the QLQ-C30 was defined as a change of 10 points or more at any post-baseline assessment. Worsening on the mPBI-sf was defined as an increase of ≥2 points from baseline.
RESULTS
The majority of participants completed the baseline and at least one subsequent PRO assessment within the trial ( = 460, 90.4% EORTC QLQ-C30; = 454, 89.2%, mBPI-sf). Patients with STS enrolled to the ANNOUNCE trial had clinically meaningful problems with physical function and pain before initiating doxorubicin. Overall, those with fewer symptoms or better function at baseline received higher cumulative doxorubicin dose throughout the study. At baseline, mean QLQ-C30 fatigue was 29.9 with a median time to first worsening of 0.9 months, and mean nausea/vomiting was 6.5 with 1.4 months until worsening; mean physical function was 78.3 with median time to worsening of 2.1 months and mean health status was 66.8 with median time to first worsening of 1.6 months. Median time to worsening of pain was 7.9 months.
CONCLUSION
Patients with advanced or metastatic sarcoma reported a relatively rapid decline in PROs during doxorubicin-based treatment, with patients with poorer symptoms at baseline (specifically fatigue), subsequently receiving less doxorubicin therapy. The availability of detailed summary data from the patient perspective during doxorubicin-based treatment may inform future care of these patients and can provide a resource for the development of PRO endpoints in future trials.
PubMed: 35547106
DOI: 10.1177/20363613221100033 -
P & T : a Peer-reviewed Journal For... Jul 2018Soft tissue sarcomas represent a group of heterogeneous mesenchymal tumors that occur rarely in adults. While a variety of histological subtypes exist, some of the most...
Soft tissue sarcomas represent a group of heterogeneous mesenchymal tumors that occur rarely in adults. While a variety of histological subtypes exist, some of the most common are leiomyosarcoma and liposarcoma. For eligible patients, standard first-line treatment of metastatic disease has typically comprised anthracycline-containing regimens. While traditional cytotoxic chemotherapy has been the mainstay of treatment in metastatic soft tissue sarcoma, emerging targeted and novel therapies are creating new frontiers of treatment for a variety of histological subtypes. Olaratumab (Lartruvo, Eli Lilly) in combination with doxorubicin represents a new potential first-line treatment option. Second-line therapy is often histology-driven, and novel treatment options include trabectedin (Yondelis, Janssen) and eribulin (Halaven, Eisai). This review discusses the diagnosis, role of chemotherapy in unresectable and metastatic disease, and role of emerging therapies in the treatment of metastatic soft tissue sarcoma.
PubMed: 30013298
DOI: No ID Found