Pazopanib for metastatic soft-tissue sarcoma: A multicenter retrospective study

2020 ◽  
pp. 107815522092407
Author(s):  
Sinan Koca ◽  
Mehmet Beşiroğlu ◽  
Melike Özçelik ◽  
Mustafa Karaca ◽  
Mehmet Bilici ◽  
...  
Keyword(s):  
Overall Survival ◽  
Weight Loss ◽  
Retrospective Study ◽  
Soft Tissue ◽  
Kinase Inhibitor ◽  
Single Agent ◽  
Real Life ◽  
Soft Tissue Sarcomas ◽  
Progression Free Survival ◽  
Free Survival

Purpose Soft tissue sarcomas are associated with a poor prognosis and low chemotherapeutic efficiency. Pazopanib is an orally available multi-tyrosine kinase inhibitor that was explored in patients with non-adipocytic advanced soft tissue sarcomas. The aim of this retrospective study was to evaluate the real life data of single-agent pazopanib efficacy and safety for soft tissue sarcomas in the Turkish population. Materials and methods We evaluated a total of 103 patients (41 males, 62 females) who received pazopanib for advanced non-adipocytic soft tissue sarcomas diagnosis in eight centers of Turkey, retrospectively. The pazopanib dose was 800 mg once daily. Progression-free survival, overall survival, and adverse events were analyzed. Results The median age was 50 years (range, 38–58). Majority of the patients had leimyosarcoma (41%). Median progression-free survival was 4.3 months, and the median overall survival was 10.1 months. The main common toxicities were fatigue, anorexia, weight loss, nausea, hypertension, and grade ≥3 toxicities were fatigue, anorexia, weight loss, and liver disorder. Conclusion Pazopanib is an efficient and tolerable agent and is well tolerated in good performance status patients with relapsed, advanced non-adipocytic soft tissue sarcomas.

Phase III Trial of Two Investigational Schedules of Ifosfamide Compared With Standard-Dose Doxorubicin in Advanced or Metastatic Soft Tissue Sarcoma: A European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study

2007 ◽  
Vol 25 (21) ◽  
pp. 3144-3150 ◽  
Author(s):  
Paul Lorigan ◽  
Jaap Verweij ◽  
Zsuzsa Papai ◽  
Sjoerd Rodenhuis ◽  
Axel Le Cesne ◽  
...  
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Standard Dose ◽  
Single Agent ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Advanced Soft Tissue Sarcoma ◽  
Phase Iii Trial ◽  
Free Survival

Purpose Single-agent doxorubicin remains the standard treatment for advanced soft tissue sarcomas. Combining doxorubicin with standard-dose ifosfamide has not been shown to improve survival and is associated with a significantly increased toxicity; it is not known whether higher dose single-agent ifosfamide is superior to doxorubicin. Patients and Methods This randomized prospective multicenter phase III trial was designed to compare progression-free survival of patients with advanced soft tissue sarcoma receiving either regimen of standard doxorubicin 75 mg/m2 every 21 days, ifosfamide 9 g/m2 over 3 days continuous infusion, or ifosfamide 3 g/m2 per day in 3 hours over 3 days. The primary end point was progression-free survival. Secondary end points included overall survival, response rate, and toxicity. Results The study included 326 patients. Grade 4 leukopenia, neutropenia, febrile neutropenia, and encephalopathy were more frequent in the ifosfamide arms. Progression-free survival, overall survival, and response rates were not significantly different between the three arms. An independent data monitoring committee reviewed the interim data and recommended early closure of the trial for futility (ie, no significant difference would be shown). Conclusion Single-agent doxorubicin remains the treatment of choice for patients with advanced soft tissue sarcoma.

scholarly journals Efficacy and Safety of Trabectedin in Patients with Soft Tissue Sarcoma: A Bicentric Retrospective Analysis.

2021 ◽  
Author(s):  
Chaigneau Loïc ◽  
Jary Marine ◽  
Nerich Virginie ◽  
Hervieu Alice ◽  
Aubry Sébastien ◽  
...  
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Soft Tissue Sarcomas ◽  
Progression Free Survival ◽  
Myxoid Liposarcoma ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Heterogenous Group ◽  
End Of Treatment ◽  
Low Toxicity

Abstract Background: Soft tissue sarcomas (STS) are a rare and heterogenous group of tumors, with poor prognostic, judging from their frequency to relapse. Few drugs are available. Since 2007, trabectedin got approval after failure of anthracyclines and ifosfamide, for advanced or metastatic STS.Patients and Methods: This retrospective study describes effects of trabectedin on survival, response, and toxicity, in STS patients. One hundred twenty-nine patients treated between 2002 and 2019 were analysed, from two French centers. All patients were tested for toxicities, and efficacy was assessed in patients exposed to at least 2 cycles of trabectedin.Results: Three median cycles were administered per patient (1-79). Among the 115 patients analysed for efficacy, the median progression free survival was 3.0 months [CI95%: 2.3 – 4.7], with an overall survival of 11.9 months [CI95%: 10.2 – 16.6]. The rate of disease control was 45.2% at the end of treatment. Myxoid liposarcoma (n = 11) was the histology subtype that benefited most from this chemotherapy with median progression free survival and an overall survival of 13.3 months [CI95%: 2.3 – 18.7] and 27.8 months [CI95%: 3.2 – 64.7], respectively. Adverse events were manageable. Conclusion: Efficacy of trabectedin is confirmed in terms of clinical benefit and low toxicity, especially for myxoid liposarcoma.

scholarly journals Retrospective Analysis of Clinicopathologic and Management Aspects of Soft Tissue Sarcoma

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
T H Kamel ◽  
A M Adel ◽  
R M Faheim ◽  
R Hegazy
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Soft Tissue Sarcomas ◽  
Progression Free Survival ◽  
Disease Status ◽  
Free Survival ◽  
Factors Affecting ◽  
The Mean ◽  
Highly Correlated ◽  
Prognostic And Predictive Factors

Abstract Background Soft tissue sarcomas (STS) are a group of rare aggressive tumors of mesenchymal origin, separated into over 50 different subtypes by histological and molecular classifications, In this analysis we evaluated the clinicopathologic and management aspects of STS. We analyzed the prognostic and predictive factors affecting both OS & PFS. Patients and Methods Medical records of 92 patients with STS were reviewed retrospectively. Overall survival (OS) and progression free survival (PFS) were estimated and factors potentially influencing these outcomes were analyzed. Results The mean age of patients was 45 +- 15.95 years (range 16-84 years). Median OS was 35.6 +_ 5.2 months and median PFS was 10.2 months. Age was assessed as a predictive factor for OS and patients <50 years had higher median OS (42.3 months) compared to patients >50 years’ old who had median OS (13.2 months) with no statically significance (P = 0.069). Also patients ≤50 years had median PFS (12.1 months’ vs 10.1 months) in patients ≥ 50 years with no statistically significance on PFS type. Type of pathology was also highly significantly correlated to overall survival (P = 0.000), liposarcoma had improved OS (42.3 months) compared to other histopathological subtypes. However, it showed no statistically significance to PFS (P = 0.036) with higher median PFS in liposarcoma (22.3 months) compared to other histopathological subtypes. Conclusion Mean age was found to be 45.9 +- 15 years old, with type of pathology. Histopathological subtypes and disease status were assessed as predictive and prognostic factor and were found to be highly correlated to OS. Effect of RTH on OS and PFS is well noted

The real-life outcome of pazopanib in patients with advanced soft tissue sarcoma: A retrospective cross-sectional study of a Turkish cohort

2020 ◽  
Vol 26 (7) ◽  
pp. 1657-1666
Author(s):  
Mustafa Karaağaç ◽  
Yasin Sezgin ◽  
Melek Karakurt Eryılmaz ◽  
Murat Araz ◽  
Muhammet Ali Kaplan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Performance Status ◽  
Soft Tissue Sarcomas ◽  
Progression Free Survival ◽  
First Line ◽  
Advanced Soft Tissue Sarcoma ◽  
Free Survival ◽  
Common Grade

Introduction Soft tissue sarcomas are a heterogeneous and rare group of cancers with a short median overall survival despite the chemotherapy. Pazopanib has approval for the treatment of advanced soft tissue sarcoma. We aimed to investigate the clinical outcomes of Turkish patients with advanced soft tissue sarcoma who received pazopanib. Patients and methods This was a retrospective study. The inclusion criteria were: ≥18 years of age, having histologically proven advanced soft tissue sarcoma and receiving pazopanib at least one day. Results A total of 79 patients were assessed in this study. The median age was 49.6 years. The average dose intensity of pazopanib was 767 mg (400–800). The median duration of pazopanib treatment was 6.11 months. Fourteen patients (17.7%) used pazopanib at first line for advanced soft tissue sarcomas. The most common cause of discontinuation of pazopanib was the progression of the disease (89.6%). Pazopanib was well tolerated. The most common grade ≥3 side effect was anemia. The most common grade ≤2 side effects were anemia and hyperbilirubinemia. The median progression-free survival, overall survival, and follow-up were 3.97 months, 11.40 months, and 32.72 months, respectively. Female gender, good performance status, and the presence of pazopanib-induced hypothyroidism were associated with longer progression-free survival. Also, good performance status and being a responder to first-line treatment were associated with longer overall survival. Conclusions We showed that pazopanib was well tolerated and had clinical benefit in patients with advanced soft tissue sarcoma in a Turkish cohort. This is the first study that suggests pazopanib-induced hypothyroidism may act as a predictive marker for better outcomes in patients with advanced soft tissue sarcoma.

A retrospective study of primitive neuroectodermal tumor (PNET) of the kidney in a tertiary cancer center in India.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 361-361
Author(s):  
Nandini Sharrel Menon ◽  
Devanshi Kalra ◽  
Kumar Prabhash ◽  
Vanita Noronha ◽  
Santosh Menon ◽  
...  
Keyword(s):  
Overall Survival ◽  
Retrospective Study ◽  
Metastatic Disease ◽  
Tumor Size ◽  
Progression Free Survival ◽  
Adjuvant Radiation ◽  
Pathological Feature ◽  
Free Survival ◽  
Rare Tumours ◽  
Multimodality Approach

361 Background: Primitive neuroectodermal tumours (PNET) of the kidney are rare tumours with aggressive behaviour. This study was conducted to review the diagnosis and management of patients with renal PNET at our centre. Methods: This was a retrospective study conducted at a tertiary cancer care centre in Mumbai, India. The demographic and clinical data of 17 patients treated by the uro-oncology services were retrieved from electronic medical records. Descriptive analysis was performed for baseline characteristics.Overall & progression-free survival was determined using the Kaplan Meier method. Cox regression was used for multivariate analysis. Results: There were 12 male and 5 female patients in this cohort with a median age of 27 years. At diagnosis 2 patients had metastatic disease and 15 patients had non-metastatic disease. Median follow up in this cohort was 22 months (range 2-30 months). Presenting complaints were hematuria, abdominal pain, flank pain, fever, bone pain, and incidentally detected renal mass. All patients were Mic -2 positive and 13 were FLI-1 positive on immunohistochemistry. Fourteen patients underwent radical nephrectomy. One (5.9%) patient received both neoadjuvant and adjuvant chemotherapy, 8 (47.1%) received adjuvant and 2 (11.8%) received palliative chemotherapy upfront. Eight patients received adjuvant radiation to the renal bed.There was disease progression in12 patients,10 of 15 patients with non metastatic disease at diagnosis eventually developed metastasis.The median progression free survival (PFS) was 10.55 months.The pathological feature that was associated with a shorter PFS was tumor size ⩾10 cm(p = 0.044).The median overall survival was 20.04 months (95% CI 9.49 -not reached). The presence of metastasis and treatment received significantly impacted overall survival (OS). Median OS in patients with non-metastatic disease was not reached versus 14.1 months in those with metastatic disease (p = .019).The median OS in patients treated with multimodality approach was 20.11 months. Patients did not undergo surgery had a median OS of 5.45 months (p < .001) and those who did not receive any chemotherapy had a median OS of 4.57 months (p = .024).Thus, patients who received multimodality treatment had better outcomes. Conclusions: PNET kidney is an aggressive tumor which should be treated with a multimodality approach. Tumor size ⩾10 cm was an adverse prognostic factor.

scholarly journals Preoperative Radiation Therapy Followed by Reexcision May Improve Local Control and Progression-Free Survival in Unplanned Excisions of Soft Tissue Sarcomas of the Extremity and Chest-Wall

2016 ◽  
Vol 2016 ◽  
pp. 1-8
Author(s):  
Hina Saeed ◽  
David M. King ◽  
Candice A. Johnstone ◽  
John A. Charlson ◽  
Donald A. Hackbarth ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Proportional Hazards Model ◽  
Performance Status ◽  
Soft Tissue Sarcomas ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Preoperative Radiation ◽  
Free Survival ◽  
Unplanned Excision

Background. The management for unplanned excision (UE) of soft tissue sarcomas (STS) has not been established. In this study, we compare outcomes of UE versus planned excision (PE) and determine an optimal treatment for UE in STS.Methods. From 2000 to 2014 a review was performed on all patients treated with localized STS. Clinical outcomes including local recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS) were evaluated using the Kaplan-Meier estimate. Univariate (UVA) and multivariate (MVA) analyses were performed to determine prognostic variables. For MVA, Cox proportional hazards model was used.Results. 245 patients were included in the analysis. 14% underwent UE. Median follow-up was 2.8 years. The LR rate was 8.6%. The LR rate in UE was 35% versus 4.2% in PE patients (p<0.0001). 2-year PFS in UE versus PE patients was 4.2 years and 9.3 years, respectively (p=0.08). Preoperative radiation (RT) (p=0.01) and use of any RT for UE (p=0.003) led to improved PFS. On MVA, preoperative RT (p=0.04) and performance status (p=0.01) led to improved PFS.Conclusions. UEs led to decreased LC and PFS versus PE in patients with STS. The use of preoperative RT followed by reexcision improved LC and PFS in patients who had UE of their STS.

A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study.

1992 ◽  
Vol 10 (7) ◽  
pp. 1066-1073 ◽  
Author(s):  
P J Loehrer ◽  
L H Einhorn ◽  
P J Elson ◽  
E D Crawford ◽  
P Kuebler ◽  
...  
Keyword(s):  
Overall Survival ◽  
Urothelial Carcinoma ◽  
Response Rate ◽  
Combined Therapy ◽  
Single Agent ◽  
Progression Free Survival ◽  
Free Survival ◽  
Metastatic Urothelial Carcinoma ◽  
Advanced Urothelial Carcinoma ◽  
To Receive

PURPOSE A prospective randomized trial was performed to determine if the addition of methotrexate, vinblastine, and doxorubicin to cisplatin (M-VAC) imparted a response rate or a survival advantage over single-agent cisplatin in patients with advanced urothelial carcinoma. PATIENTS AND METHODS From October 1984 through May 1989, 269 patients with advanced urothelial carcinoma were entered onto this international intergroup trial and randomized to receive intravenous (IV) cisplatin (70 mg/m2) alone or with methotrexate (30 mg/m2 on days 1, 15, 22), vinblastine (3 mg/m2 on days 2, 15, 22) plus doxorubicin (30 mg/m2 on day 2). Cycles were repeated every 28 days until tumor progression or a maximum of six cycles. There were 246 fully assessable patients of whom 126 were randomized to cisplatin alone and 120 were randomized to the M-VAC regimen. RESULTS As expected, the M-VAC regimen was associated with a greater toxicity, especially leukopenia, mucositis, granulocytopenic fever, and drug-related mortality. Response rates were superior for the M-VAC regimen compared with single-agent cisplatin (39% v 12%; P less than .0001). Similarly, the progression-free survival (10.0 v 4.3 months) and overall survival (12.5 v 8.2 months) were significantly greater for the combined therapy arm. CONCLUSION Although a more toxic regimen, we found M-VAC to be superior to single-agent cisplatin with respect to response rate, duration of remission, and overall survival in patients with advanced urothelial carcinoma.

Detection and impact of minimal residual disease on outcome of chronic lymphocytic leukemia

2012 ◽  
Vol 153 (41) ◽  
pp. 1622-1628
Author(s):  
Márk Plander ◽  
Judit Skrapits ◽  
Tünde Bozsó ◽  
Tamás Szendrei ◽  
János László Iványi
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Complete Remission ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Single Agent ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Free Survival ◽  
Minimal Residual

Introduction: Minimal residual disease is associated with longer overall survival in patients with chronic lymphocytic leukemia. Aim: The aim of the authors was to determine the clinical significance of remission and minimal residual disease on the survival of patients with chronic lymphocytic leukemia. Methods: Data from 42 first-line treated patients with chronic lymphocytic leukemia were analyzed. Minimal residual disease was determined by flow cytometry. Results: Overall response and complete remission was achieved in 91%, 86%, 100% and 87%, 0%, 60% of patients with fludarabine-based combinations, single-agent fludarabine and cyclophosphamide + vincristin + prednisolone regimen, respectively. Minimal residual disease eradication was feasible only with fludarabine-based combinations in 60% of these cases. The ratio of minimal residual disease was 0.5% on average. During a median follow-up period lasting 30 months, the overall survival of patients with fludarabine-resistant disease proved to be significantly shorter (p = 0.04), while complete remission without minimal residual disease was associated with significantly longer progression free survival (p = 0.02). Conclusion: Only fludarabine-based combinations were able to eradicate minimal residual disease in patients with chronic lymphocytic leukemia. Complete remission without minimal residual disease may predict longer progression free survival in these patients. Orv. Hetil., 2012, 153, 1622–1628.

Phase III Trial of Gemcitabine Plus Tipifarnib Compared With Gemcitabine Plus Placebo in Advanced Pancreatic Cancer

2004 ◽  
Vol 22 (8) ◽  
pp. 1430-1438 ◽  
Author(s):  
E. Van Cutsem ◽  
H. van de Velde ◽  
P. Karasek ◽  
H. Oettle ◽  
W.L. Vervenne ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Single Agent ◽  
Survival Rates ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Controlled Study ◽  
Double Blind ◽  
Free Survival

Purpose To determine whether addition of the farnesyltransferase inhibitor tipifarnib (Zarnestra, R115777; Johnson and Johnson Pharmaceutical Research and Development, Beerse, Belgium) to standard gemcitabine therapy improves overall survival in advanced pancreatic cancer. Patients and Methods This randomized, double-blind, placebo-controlled study compared gemcitabine + tipifarnib versus gemcitabine + placebo in patients with advanced pancreatic adenocarcinoma previously untreated with systemic therapy. Tipifarnib was given at 200 mg bid orally continuously; gemcitabine was given at 1,000 mg/m2 intravenously weekly × 7 for 8 weeks, then weekly × 3 every 4 weeks. The primary end point was overall survival; secondary end points included 6-month and 1-year survival rates, progression-free survival, response rate, safety, and quality of life. Results Six hundred eighty-eight patients were enrolled. Baseline characteristics were well balanced between the two treatment arms. No statistically significant differences in survival parameters were observed. The median overall survival for the experimental arm was 193 v 182 days for the control arm (P = .75); 6-month and 1-year survival rates were 53% and 27% v 49% and 24% for the control arm, respectively; median progression-free survival was 112 v 109 days for the control arm. Ten drug-related deaths were reported for the experimental arm and seven for the control arm. Neutropenia and thrombocytopenia grade ≥ 3 were observed in 40% and 15% in the experimental arm versus 30% and 12% in the control arm. Incidences of nonhematologic adverse events were similar in two groups. Conclusion The combination of gemcitabine and tipifarnib has an acceptable toxicity profile but does not prolong overall survival in advanced pancreatic cancer compared with single-agent gemcitabine.

The combination of intravenous bevacizumab and metronomic oral cyclophosphamide for recurrent platinum-resistant ovarian cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5039-5039
Author(s):  
Emma L. Barber ◽  
Nikki Lynn Neubauer ◽  
Emese Zsiros ◽  
Julian C. Schink
Keyword(s):  
Overall Survival ◽  
Ovarian Carcinoma ◽  
Single Agent ◽  
Progression Free Survival ◽  
Complete Response ◽  
Response To Treatment ◽  
Ca 125 ◽  
Oral Cyclophosphamide ◽  
Free Survival ◽  
Platinum Resistant

5039 Background: This study was undertaken to determine the progression free survival and overall survival in heavily pre-treated patients with recurrent ovarian carcinoma treated with bevacizumab and metronomic oral cyclophosphamide. Methods: An IRB-approved retrospective review was performed for all patients with recurrent ovarian, fallopian tube or primary peritoneal carcinomas treated with intravenous bevacizumab 10mg/kg every 14 days and oral cyclophosphamide 50mg daily between January 2006 and December 2010. Response to treatment was determined by change in disease status according to RECIST criteria and/or CA-125 levels. Results: Sixty-six eligible patients were identified with a median age of 58 years. Fifty-five patients (83%) originally had optimal cytoreduction and all were platinum resistant. Median time from diagnosis to beginning bevacizumab and cyclophosphamide was 36 months. Median number of prior chemotherapy treatments was 7.5 (range 3-16). Eight patients (12.1%) had side effects which required discontinuing bevacizumab and cyclophosphamide, most common were hypertension, proteinuria, and fatigue. There was one bowel perforation (1.5%). A complete response was noted in 7 patients (10.6%), partial response was seen in 21 patients (31.8%) with an overall response rate of 42.4%. Fifteen patients (22.7%) had stable disease and 23 (34.8%) had disease progression. Median progression free survival (PFS) for responders was 5 months (range 2-14) and 11 months (range 4-14) for those with a complete response. Median overall survival (OS) from start of bevacizumab and cyclophosphamide for responders was 20 months (range 2-56) and 9 months (range 1-51) for nonresponders. Conclusions: Bevacizumab and cyclophosphamide is an effective, well-tolerated chemotherapy regimen in heavily pre-treated patients with recurrent ovarian carcinoma which significantly improves PFS and OS in responders. Response rates were significantly better than the rates we have reported in this same group of patients receiving topotecan (22%) or liposomal doxorubicin (25%) and were superior to reported rates for single agent bevacizumab (18%) in patients with only 2-3 prior regimens.

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