94 research outputs found
Efficacy of the combination of long-acting release octreotide and tamoxifen in patients with advanced hepatocellular carcinoma: a randomised multicentre phase III study
To assess the efficacy of the combination of long-acting release (LAR) octreotide and tamoxifen (TMX) for the treatment of advanced hepatocellular carcinoma (HCC). A total of 109 patients with advanced HCC were randomised to receive octreotide LAR combined with TMX (n=56) (experimental treatment group) or TMX alone (n=53; control group). The clinical, biological and tumoural parameters were recorded every 3 months until death. Primary end point was patient survival; secondary end points were the impact of therapy on tumour response, quality of life and variceal bleeding episodes. Univariate and multivariate analyses were performed for assessment of specific prognostic factors. The median survival was 3 months (95% CI 1.4â4.6) for the experimental treatment group and 6 months (CI 95% 2â10) for the control group (P=0.609). There was no difference in terms of α-foetoprotein (α-FP) decrease, tumour regression, improvement of quality of life and prevention of variceal bleeding between the two groups. Variables associated with a better survival in the multivariate analysis were: presence of cirrhosis, α-FP level <400ângâmlâ1 and Okuda stage I. The combination of octreotide LAR and TMX does not influence survival, tumour progression or quality of life in patients with advanced HCC
Pazopanib in advanced vascular sarcomas: an EORTC Soft Tissue and Bone Sarcoma Group (STBSG) retrospective analysis.
Background Pazopanib is a multitargeted tyrosine kinase inhibitor approved for the treatment of patients with selective subtypes of advanced soft tissue sarcoma (STS) who have previously received standard chemotherapy including anthracyclines. Data on the efficacy in vascular sarcomas are limited. The main objective of this study was to investigate the activity of pazopanib in vascular sarcomas.Patients and methods A retrospective study of patients with advanced vascular sarcomas, including angiosarcoma (AS), epithelioid hemangioendothelioma (HE) and intimal sarcoma (IS) treated with pazopanib in real life practice at EORTC centers as well as patients treated within the EORTC phase II and III clinical trials (62043/62072) was performed. Patient and tumor characteristics were collected. Response was assessed according to RECIST 1.1. and survival analysis was performed.Results Fifty-two patients were identified, 40 (76.9%), 10 (19.2%) and two (3.8%) with AS, HE and IS, respectively. The response rate was eight (20%), two (20%) and two (100%) in the AS, HE and IS subtypes, respectively. There was no significant difference in response rate between cutaneous and non-cutaneous AS and similarly between radiation-associated and non-radiation-associated AS. Median progression-free survival (PFS) and median overall survival (OS; from commencing pazopanib) were three months (95% CI 2.1-4.4) and 9.9 months (95% CI 6.5-11.3) in AS, respectively.Conclusion The activity of pazopanib in AS is comparable to its reported activity in other STS subtypes. In this study, the activity of pazopanib was similar in cutaneous/non-cutaneous and in radiation/non-radiation-associated AS. In addition, pazopanib showed promising activity in HE and IS, worthy of further evaluation
Doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, or doxorubicin alone as a firstâline treatment for advanced leiomyosarcoma: A propensity score matching analysis from the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group
Background
The optimal treatment for advanced leiomyosarcoma is still debated. Given histotypeâspecific prospective controlled data lacking, this study retrospectively evaluated doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, and doxorubicin alone as firstâline treatments for advanced/metastatic leiomyosarcoma treated at European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group (EORTCâSTBSG) sites.
Methods
The inclusion criteria were a confirmed histological diagnosis, treatment between January 2010 and December 2015, measurable disease (Response Evaluation Criteria in Solid Tumors 1.1), an Eastern Cooperative Oncology Group performance status â€2, and an age â„ 18 years. The endpoints were progressionâfree survival (PFS), overall survival (OS), and overall response rate (ORR). PFS was analyzed with methods for intervalâcensored data. Patients were matched according to their propensity scores, which were estimated with a logistic regression model accounting for histology, grade, age, sex, performance status, tumor site, and tumor extent.
Results
Three hundred three patients from 18 EORTCâSTBSG sites were identified. One hundred seventeen (39%) received doxorubicin plus dacarbazine, 71 (23%) received doxorubicin plus ifosfamide, and 115 (38%) received doxorubicin. In the 2:1:2 propensity scoreâmatched population (205 patients), the estimated median PFS was 9.2 months (95% confidence interval [CI], 5.2â9.7 months), 8.2 months (95% CI, 5.2â10.1 months), and 4.8 months (95% CI, 2.3â6.0 months) with ORRs of 30.9%, 19.5%, and 25.6% for doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, and doxorubicin alone, respectively. PFS was significantly longer with doxorubicin plus dacarbazine versus doxorubicin (hazard ratio [HR], 0.72; 95% CI, 0.52â0.99). Doxorubicin plus dacarbazine was associated with longer OS (median, 36.8 months; 95% CI, 27.9â47.2 months) in comparison with both doxorubicin plus ifosfamide (median, 21.9 months; 95% CI, 16.7â33.4 months; HR, 0.65; 95% CI, 0.40â1.06) and doxorubicin (median, 30.3 months; 95% CI, 21.0â36.3 months; HR, 0.66; 95% CI, 0.43â0.99). Adjusted analyses retained an effect for PFS but not for OS. None of the factors selected for multivariate analysis had a significant interaction with the received treatment for both PFS and OS.
Conclusions
This is the largest retrospective study of firstâline treatment for advanced leiomyosarcoma. In the propensity scoreâmatched population, doxorubicin and dacarbazine showed favorable activity in terms of both ORR and PFS and warrants further evaluation in prospective trials
Receptor Tyrosine Kinases in Osteosarcoma: 2019 Update
The primary conclusions of our 2014 contribution to this series were as follows:
Multiple receptor tyrosine kinases (RTKs) likely contribute to aggressive phenotypes in osteosarcoma and, therefore, inhibition of multiple RTKs is likely necessary for successful clinical outcomes.
Inhibition of multiple RTKs may also be useful to overcome resistance to inhibitors of individual RTKs as well as resistance to conventional chemotherapies.
Different combinations of RTKs are likely important in individual patients.
AXL, EPHB2, FGFR2, IGF1R, and RET were identified as promising therapeutic targets by our in vitro phosphoproteomic/siRNA screen of 42 RTKs in the highly metastatic LM7 and 143B human osteosarcoma cell lines.
This chapter is intended to provide an update on these topics as well as the large number of osteosarcoma clinical studies of inhibitors of multiple tyrosine kinases (multi-TKIs) that were recently published
La Borie (Saint-Papoul, Aude) : un gisement exceptionnel dans l'ĂocĂšne basal du Sud de la France
International audienceThe fossil locality of "La Borie" has revealed a unique fauna in the early Eocene of Southern France. This preliminary study has identified 35 vertebrate taxa, including some never found before in the South of France (the crocodile Kentisuchus), Southern Europe (the tillodont Plesiesthonyx) or the western part of Eurasia (the wading bird Eogrus). A new genus of creodont, a new primate and probably a new species of Neochelys are identified. Abundant material relating to the ceratomorph Lophiaspis and the giant groundbird Gastornis is reported. The sedimentological, floral and faunal data provide a paleoenvironment of floodplain savannah with a humid tropical climate, with a weakly marked dry season. An age close to the MP 8+9 reference level is proposed, based on the presence of several taxa characteristic of the earliest Eocene.Le gisement de La Borie a livrĂ© une faune unique dans l'ĂocĂšne infĂ©rieur du Sud de la France. Cette Ă©tude prĂ©liminaire y reconnaĂźt 35 taxons de vertĂ©brĂ©s, dont certains inĂ©dits pour le Sud de la France (le crocodile Kentisuchus), le Sud de l'Europe (le tillodonte Plesiesthonyx) ou la partie occidentale du continent eurasiatique (l'Ă©chassier Eogrus). Un nouveau genre de crĂ©odonte, de primate, et vraisemblablement une nouvelle espĂšce de Neochelys sont identifiĂ©s. Un matĂ©riel abondant du cĂ©ratomorphe Lophiaspis et de l'oiseau gĂ©ant Gastornis est signalĂ©. Les donnĂ©es sĂ©dimentologiques, faunistiques et floristiques convergent pour proposer un palĂ©oenvironnement de savane arborĂ©e de plaine alluviale en climat tropical humide, avec une saison sĂšche peu marquĂ©e. Plusieurs taxons militent en faveur d'un Ăąge proche du niveau-repĂšre mammalien MP 8+9
La Borie (Saint-Papoul, Aude) : un gisement exceptionnel dans l'Eocene basal du Sud de la France
International audienceLe gisement de La Borie a livrĂ© une faune unique dans l'ĂocĂšne infĂ©rieur du Sud de la France. Cette Ă©tude prĂ©liminaire y reconnaĂźt 35 taxons de vertĂ©brĂ©s, dont certains inĂ©dits pour le Sud de la France (le crocodile Kentisuchus), le Sud de l'Europe (le tillodonte Plesiesthonyx) ou la partie occidentale du continent eurasiatique (l'Ă©chassier Eogrus). Un nouveau genre de crĂ©odonte, de primate, et vraisemblablement une nouvelle espĂšce de Neochelys sont identifiĂ©s. Un matĂ©riel abondant du cĂ©ratomorphe Lophiaspis et de l'oiseau gĂ©ant Gastornis est signalĂ©. Les donnĂ©es sĂ©dimentologiques, faunistiques et floristiques convergent pour proposer un palĂ©oenvironnement de savane arborĂ©e de plaine alluviale en climat tropical humide, avec une saison sĂšche peu marquĂ©e. Plusieurs taxons militent en faveur d'un Ăąge proche du niveau-repĂšre mammalien MP 8+9
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