-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Solitary Fibrous Tumor is a rare type of soft tissue tumor of intermediate malignant potential which may recur or metastasize in 15-20% of cases. Data on the management of patients with advanced SFT is scarce: chemotherapy has been described as ineffective, while recent data suggests that anti-angiogenic therapies may be more efficient. METHODS: We conducted a retrospective study on patients treated for advanced SFT at a single institution: from January 1994 to December 2011, 30 patients were treated in the Centre Leon Berard for an advanced SFT. RESULTS: Twenty-three patients received cytotoxic chemotherapy as first-line therapy. Best responses were 2 (9%) partial responses, 13 (57%) stable diseases (SD) and 8 (35%) progressive diseases (PD). Median Progression Free Survival (PFS) was 5.2 (95%CI: 3.2-7.1) months and 9 patients were free of progression at 6 months. Ten patients received an anti-angiogenic treatment (sunitinib or pazopanib) as a 2nd, 3rd or 4th line. Best responses were 5 SD and 5 PD; median PFS was 5.1 months (95%CI 0.7-9.6). Four patients (36%) were progression-free for more than 6 months. Two patients receiving pazopanib were without progression at 6 and 8 months and two patients receiving sunitinib were free of progression at 30 months. CONCLUSION: Response rate with standard chemotherapy was low and PFS appear similar between cytotoxic chemotherapy and anti-angiogenic agents.
BMC Cancer 03/2013; 13(1):109. · 3.01 Impact Factor
-
Irène Asmane,
Emmanuel Watkin,
Laurent Alberti,
Adeline Duc,
Perrine Marec-Berard,
Isabelle Ray-Coquard,
Philippe Cassier,
Anne-Valérie Decouvelaere, Dominique Ranchère,
Jean-Emmanuel Kurtz,
Jean-Pierre Bergerat,
Jean-Yves Blay
[show abstract]
[hide abstract]
ABSTRACT: A minority of patients with advanced sarcoma achieve prolonged progression free survival (PFS) with insulin growth factor type 1 receptor (IGF-1R) monoclonal antibody (Ab) therapy. A biomarker identifying those patients beforehand would be useful to select patients for the development of these agents.
This single centre series includes patients with unresectable or metastatic soft tissue sarcomas (STS), Ewing sarcoma (ES) and osteosarcoma treated with IGF-1R Ab (R1507, IMC-A12, SCH 717454 and CP-751.871) in the Centre Léon Bérard. Tumour samples were analysed by immunohistochemistry for expression of IGF-1R, insulin-like growth factor binding protein type 3 (IGFBP-3), Ki67, epidermal growth factor receptor (HER1) and human epidermal growth factor receptor 2 (HER2). Predictive factors for PFS and overall survival (OS) were investigated.
All tumour samples had a positive IGF-1R immunostaining on 60% to 100% of tumour cells. IGFBP-3 immunostaining was observed in 12 (75%) samples with 5% to 100% of positive cells. IGF-1R immunostaining was nuclear (n=9, 56%), cytoplasmic (n=4, 25%), or nuclear +cytoplasmic (n=3, 19%). Neither IGFBP-3 expression, nor Ki67 was correlated to PFS. HER2 and HER1 staining were positive in 0 and 2 samples respectively (both primary resistant to IGF-1R Ab therapy). Exclusive intra-nuclear immunoreactivity for IGF-1R was significantly associated with a better PFS (p=0.01) and OS (p=0.007).
Exclusive nuclear localisation of IGF-1R is an easily testable biomarker associated with a better PFS and OS for patients treated with IGF-1R Ab therapy. Nuclear localisation of IGF-1R in tumour cells might be a hallmark of pathway activation.
European journal of cancer (Oxford, England: 1990) 06/2012; 48(16):3027-35. · 4.12 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Alterations of the p53 pathway are among the most frequent aberrations observed in human cancers. We have performed an exhaustive analysis of TP53, p14, p15, and p16 status in a large series of 143 soft tissue sarcomas, rare tumors accounting for around 1% of all adult cancers, with complex genetics. For this purpose, we performed genomic studies, combining sequencing, copy number assessment, and expression analyses. TP53 mutations and deletions are more frequent in leiomyosarcomas than in undifferentiated pleomorphic sarcomas. Moreover, 50% of leiomyosarcomas present TP53 biallelic inactivation, whereas most undifferentiated pleomorphic sarcomas retain one wild-type TP53 allele (87.2%). The spectrum of mutations between these two groups of sarcomas is different, particularly with a higher rate of complex mutations in undifferentiated pleomorphic sarcomas. Most tumors without TP53 alteration exhibit a deletion of p14 and/or lack of mRNA expression, suggesting that p14 loss could be an alternative genotype for direct TP53 inactivation. Nevertheless, the fact that even in tumors altered for TP53, we could not detect p14 protein suggests that other p14 functions, independent of p53, could be implicated in sarcoma oncogenesis. In addition, both p15 and p16 are frequently codeleted or transcriptionally co-inhibited with p14, essentially in tumors with two wild-type TP53 alleles. Conversely, in TP53-altered tumors, p15 and p16 are well expressed, a feature not incompatible with an oncogenic process.
American Journal Of Pathology 10/2010; 177(4):2080-90. · 4.89 Impact Factor
-
Jérôme Fayette,
Philippe Cassier,
Laura Brousseau,
Armelle Dufresne,
Isabelle Ray Coquard,
Laurent Alberti,
Pierre Méeus,
Anne-Valérie Decouvelaere,
Marie-Pierre Sunyach, Dominique Ranchère,
Jean-Yves Bla
[show abstract]
[hide abstract]
ABSTRACT: Thirty to 50% of patients with adult type soft tissue sarcoma will develop metastasis. At this stage, systemic chemotherapy
is then generally proposed when a complete resection of all metastasis is not feasible (Clark et al. 2005). The two most active therapeutic drugs for advanced soft tissue sarcomas are doxorubicin and ifosfamide; dacarbazine although
considered as the third active agent, actually shows a marginal activity. Initial response rates to doxorubicin single agent
regimens are 10–30% with 5–8% long term survivors (Blay et al. 2003, 2004). The combination of doxorubicin with ifosfamide has yielded higher response rate (25–70%), but with no survival improvement.
After failure of doxorubicin and ifosfamide, few therapeutic options are available. The combination of gemcitabine and docetaxel
was reported to induce high response rates and progression free survival (PFS) in leiomyosarcomas (Bay et al. 2006). ET-743, trabectedin, Yondelis®, is a tetrahydro-isoquinoline alkaloid isolated from Ectenascidia turbinata, a tunicate that grows on mangrove roots throughout the Caribbean sea. ET-743 interferes with the activity of several transcription
factors and traps protein from the nucleotide excision repair (NER) system, thus resulting in DNA damage, modulation of expression
of various genes, and blockade of cells in G2-M phase. After failure of doxorubicin and/or ifosfamide, as well as in first
line treatment, ET-743 at 1.5 mg/m2 in 24 h CI every 21 days yielded an overall response rate close to 8% and 30–40% stabilisation rates. Leiomyosarcomas, liposarcomas
(in particular myxoid liposarcomas), and synovial sarcomas may be the more sensitive histotypes. The major toxicities of ET-743
are hepatic, through biliary duct destruction, and hematologic. They are not cumulative. In vitro, ET-743 exerts synergistic
cytotoxic activity with doxorubicin or cisplatin, and in vivo with irinotecan. Phase I combination studies are in currently
progress. We detail all these aspects of ET-743.
12/2009: pages 450-460;
-
Jérôme Fayette,
Helen Boyle,
Sylvie Chabaud,
Bertrand Favier,
Catherine Engel,
Philippe Cassier,
Philippe Thiesse,
Pierre Méeus,
Marie-Pierre Sunyach,
Gualter Vaz,
Isabelle Ray-Coquard, Dominique Ranchère,
Anne-Valérie Decouvelaere,
Laurent Alberti,
David Pérol,
Jean-Yves Blay
[show abstract]
[hide abstract]
ABSTRACT: Trabectedin was recently approved for patients failing doxorubicin, the standard treatment for advanced/metastatic sarcoma. This retrospective study aimed to compare trabectedin efficacy between compassionate use in unselected patients and clinical trials. From May 1999 to January 2006, 92 patients were treated at the Centre Léon Bérard, either in phase II studies or on a named patient compassionate basis. All cases were retrospectively analyzed to assess trabectedin efficacy in terms of response, progression-free, and overall survival.The objective response rate was 10% (N=9): 4% (N=2) for patients treated in compassionate use program and 16% (N=7) for those in clinical trials (P=0.18); 26 (28%) patients had stable disease for at least 6 months, 11 (23%) in the compassionate group and 15 (33%) in clinical trials. Median progression-free and overall survivals were, respectively, 2.2 [95% confidence interval (CI): 1.9-3.6] and 8.9 (95% CI: 6.4-14.2) months for all patients, 2.3 (95% CI: 1.9-4.3) and 10.4 (95% CI: 6.9-24.2) months for patients in clinical trials and 1.8 (95% CI: 1.4-3.4) and 6.4 (95% CI: 3.3-14.2) months for patients under compassionate treatment. In this retrospective analysis, the reported grade 3-4 toxicities were increased transaminase (34 patients, 37%) and neutropenia (38 patients; 42%). Higher efficacy was observed in phase II studies than with compassionate treatment, but no significant difference remained after adjustment in multivariate analysis for performance status, a well-established prognosis factor. The safety and tolerability of trabectedin shown in clinical trials is confirmed for patients in real-life situation treated in compassionate use programs, but its benefit is higher for patients with performance status 0-1.
Anti-cancer drugs 11/2009; 21(1):113-9. · 2.23 Impact Factor
-
Laila Chbani,
Louis Guillou,
Philippe Terrier,
Anne Valérie Decouvelaere,
Fleur Grégoire,
Marie José Terrier-Lacombe, Dominique Ranchère,
Yves Marie Robin,
Françoise Collin,
Paul Fréneaux,
Jean-Michel Coindre
[show abstract]
[hide abstract]
ABSTRACT: Epithelioid sarcoma (ES) is rare with a poor prognosis and for which a loss of INI1 expression has been recently reported. We report a study of 106 cases with clinical, histologic, and immunohistochemical data, including INI1 expression, and follow-up data. Of the 106 cases, 70 were the conventional subtype and 36 the large cell subtype. INI1 was negative in 86 cases (81.1%): 57 (81%) of 70 conventional and 29 (81%) of 36 large cell subtypes. Treatment modalities were available for 76 and follow-up for 80 patients. Of the 80 patients, 43 (54%) experienced metastasis and 25 (31%) died of the disease. Univariate analysis indicated that tumor size and mitotic index were significant for metastasis-free survival, whereas proximal location, tumor size, tumor multifocality, and mitotic index were significant for overall survival. Loss of expression of INI1 is frequent in the conventional and large cell subtypes of ES and can be used as a diagnostic marker, but it has no prognostic impact.
American Journal of Clinical Pathology 03/2009; 131(2):222-7. · 2.60 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Superficial primitive Ewing's sarcomas are rare and have been reported to be of favorable prognosis compared to conventional deep-seated tumors. In the skin and subcutis, the diagnosis is often difficult, and performing molecular cytogenetic techniques may be helpful. We performed a retrospective analysis of 14 cases of superficial Ewing's sarcomas, all confirmed by molecular cytogenetics. Clinical, histological, immunohistochemical, molecular cytogenetic, therapeutic, and follow-up data are reported. There were 11 female and 3 male patients aged from 12 to 77 years (median: 17 years). Seven tumors occurred in the extremities, five in the trunk wall, and two in the head. Tumor size ranged from 1 to 5 cm (median, 3 cm). They were all small round-cell proliferations with a strong membranous positivity for CD99. Ewing's sarcoma translocations/fusion gene transcripts were detected in eight cases, both by FISH and reverse transcriptase (RT)-PCR. Four tumors were positive by RT-PCR alone (FISH not done in three cases and not interpretable in one case), and two cases were positive by FISH alone (RT-PCR not done). Surgical resection was performed in all patients. Chemotherapy was given in ten patients and radiotherapy in six. At last medical examination (median follow-up, 47 months), two patients who underwent surgical resection alone had died from the tumor. Our results confirm that superficial Ewing's sarcomas are of good prognosis. Given the difficulty of the diagnosis and the importance of an adapted treatment, a confirmation of the diagnosis by molecular or cytogenetic techniques is recommended when dealing with a superficial tumor.
Modern Pathology 10/2008; 22(1):87-94. · 4.79 Impact Factor
-
Philippe A Cassier,
Armelle Dufresne,
Samia Arifi,
Hiba El Sayadi,
Intidar Labidi,
Isabelle Ray-Coquard,
Séverine Tabone,
Pierre Méeus, Dominique Ranchère,
Marie-Pierre Sunyach,
Anne-Valérie Decouvelaere,
Laurent Alberti,
Jean-Yves Blay
[show abstract]
[hide abstract]
ABSTRACT: The molecular hallmark of gastrointestinal stromal tumours (GISTs), the mutation of the KIT gene, was discovered 10 years ago. GISTs have since been recognized as separate pathological entities among sarcomas, and have become a model for targeted treatment of solid tumours. Imatinib mesilate, which was approved in 2002 for the treatment of patients with advanced GIST, has dramatically changed the course of the disease.
This article will focus on the development of imatinib mesilate in the treatment of patients with GIST.
A Pubmed search was performed using the keywords 'imatinib', 'gastrointestinal stromal', 'GIST', 'KIT' and 'PDGFR'. Websites of the American Society of Clinical Oncology and the European Society of Medical Oncology were searched for data reported in abstract form at recent symposiums. Personal communications from opinion leaders were sought for additional information that might be relevant.
Imatinib has changed the clinical course of patients with advanced GISTs and further development in the adjuvant setting as well as prospective assessment of predictive factors are the current focus of ongoing research.
Expert Opinion on Pharmacotherapy 06/2008; 9(7):1211-22. · 3.20 Impact Factor
-
Samia Arifi,
Hiba El Sayadi,
Armelle Dufresne,
Isabelle Ray-Coquard,
Jérôme Fayette,
Pierre Méeus, Dominique Ranchère,
Anne-Valérie Decouvelaere,
Laurent Alberti,
Séverine Tabone-Eglinger,
Jean-Yves Blay,
Philippe Cassier
[show abstract]
[hide abstract]
ABSTRACT: Imatinib mesylate (Gleevec, Glivec, Novartis, Basel, Switzerland) is a small molecule inhibitor of the tyrosine kinase c-abl, c-kit and the platelet derived growth factor receptor (PDGFR). Imatinib was developed for the treatment of chronic myeloid leukaemia (CML) but was approved both in Europe and the US fro the treatment of CML and gastrointestinal stromal tumors (GIST). Given its activity against both c-kit and PDGFR kinases and its remarkable safety profile, imatinib has been 'tried' in several solid tumors; results however have often been deceiving. We review the current data regarding the activity of imatinib in solid tumors, including GIST.
Bulletin du cancer 02/2008; 95(1):99-106. · 0.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: ET-743 (ecteinascidin-743, trabectedin, Yondelis) is a natural marine product that has shown clinical activity in sarcoma. This paper reviews the current knowledge on this compound.
ET-743 interferes with several transcription factors, traps protein from the nucleotide-excision repair system, thus resulting in DNA damage, modulates gene expression, and blocks cells in the G2-M phase. In the clinical setting, after failure of standard treatment, ET-743 at 1.5 mg/m2 in 24 h continuous infusion every 21 days yielded an overall response rate close to 8% and stabilization rates of 30-40%, some lasting beyond 3 years. Leiomyosarcomas, liposarcomas, and synovial sarcomas may be the more sensitive histotypes. The major toxicities of ET-743 are hepatic--through biliary duct destruction--and hematologic. They are not cumulative and a significant number of patients may receive 12 courses or more. In a randomized Phase II study testing weekly ET-743 with treatment every 3 weeks, an improved progression-free survival rate was observed in the 3-weekly arm; the results of the follow-up Phase III trial should be available at the American Society of Clinical Oncology meeting of 2006. Phase I combination studies are in currently progress.
ET-743 is a novel active drug for sarcoma which yields prolonged disease-free survival in subsets of patients.
Current Opinion in Oncology 08/2006; 18(4):347-53. · 4.10 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Ecteinascidin-743 (ET-743) is a natural product derived from the marine tunicate Ectenascidia turbinate. ET- 743 binds in the minor groove of DNA, blocks transcrip- tion factors activity, and traps protein from the nucleo- tide excision repair system, thus blocking cells in G2-M phase. ET-743 demonstrated cytotoxic activity at very low concentrations against sarcoma cell lines in pre- clinical studies. In several phase II clinical studies in patients with advanced sarcoma failing conventional doxorubicin- and ifosfamide-based chemotherapy, ET-743 delivered by continuous intravenous 24-hour infusion at a dose of 1,500 μg/m 2 every 21 days yielded
Current Opinion in Oncology - CURR OPIN ONCOL. 01/2006; 18(4):347-353.
-
Jean-Yves Blay,
Bruno Landi,
Sylvie Bonvalot,
Geneviève Monges,
Isabelle Ray-Coquard,
Florence Duffaud,
Nguyen Binh Bui,
Roland Bugat,
Jean-Alain Chayvialle,
Philippe Rougier, [......],
Nathalie Lassau,
Daniel Vanel,
Bernard Nordlinger,
Eberhard Stoeckle,
Pierre Meeus,
Jean-Michel Coindre,
Jean-Yves Scoazec,
Jean-François Emile, Dominique Ranchère,
Axel Le Cesne
[show abstract]
[hide abstract]
ABSTRACT: The management of gastrointestinal stromal tumors (GIST) has evolved very rapidly in the last years. A national consensus meeting was therefore organized in order to identify the optimal management procedures for patients with GIST in localized and advanced stages.
A panel of different specialties, including pathology, molecular biology, imaging, surgery, gastroenterology, medical oncology reviewed the current literature, in particular the recent Lugano conference, to identify consensus points and topics for future research in four different working groups: pathology and molecular biology, early management of small tumors and imaging, surgery, and medical treatment. Consensus points were categorized according to the Standard Options Recommendations (SOR) of the French Federation of Cancer Centers.
The standard histological examination with immunohistochemical analysis using CD117, CD34, PS100, desmin and smooth muscle actin is considered standard. Molecular biology for the identification of KIT and PDGFRA mutation is advisable for GIST with negative CD117 staining, and otherwise is considered a research procedure. Complete tumor resection with negative tumor margins is the standard surgical treatment. Adjuvant imatinib after optimal tumor resection as well as neo-adjuvant imatinib remain experimental approaches to be performed within prospective clinical studies. Imatinib should be started at the date of diagnosis of metastatic relapse and given until development of intolerance or progressive disease. Resection of metastases is also considered as an experimental procedure which can not be recommended routinely. The criteria for tumor response to imatinib should include not only tumor size reduction or disease stabilization, but also reduction of tumor density (Hounsfield units) on computed tomography, metabolic activity (i.e. reduction of FDG uptake on positron emission tomography), and reduction of vascularisation of the tumors using contrast enhanced ultrasound evaluation. An increase in tumor size may be associated with pathologic response to imatinib therapy, and available survival data indicate that the survival of these patients is similar to that of patients with conventional tumor response.
Consensus points in clinical management of GIST in this national conference adopted the majority of consensus points published in the Lugano conference. This multidisciplinary work will be published in the reference oncology, gastroenterology, and pathology journals in French languages.
Bulletin du cancer 11/2005; 92(10):907-18. · 0.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma. Nevertheless, the validity of this heterogeneous pathological entity has been recurrently questioned by pathologists. Recently, analyses by comparative genomic hybridization (CGH) of a large series of MFHs suggested that MFHs consist of morphologic modulation of other poorly differentiated sarcomas like leiomyosarcomas (LMS) or dedifferentiated liposarcomas (DLPS). We report here an analysis by CGH of 22 myxoid MFHs (mMFH), one of the five histological subtypes of MFH, and of nine pleomorphic liposarcomas (pLPS), a rare poorly differentiated LPS. The chromosome imbalances encountered in the series of mMFH were very similar to those observed in the series of pLPS studied in the laboratory and in the series of 14 pLPS published in the literature. The most frequent gains involved chromosome subregions: pericentromeric regions of 1, 5p, 19p, 19q and 20q. Losses found in the chromosomal arms 1q, 2q, 3p, 4q, 10q, 11q and 13q were also recurrent. The use of a clustering software did not separate the two pathological groups (mMFH and pLPS) on the basis of genomic data. Moreover, pLPS-mMFH represented, according to the clustering software results, an entity clearly distinguished from other soft tissue sarcomas, LMS in particular, with which they share common genetic aberrations. Additional studies are needed to identify genes targeted by these genomic aberrations, and implicated in the oncogenesis of these tumor subtypes. The characterization of common gene alterations in both tumor groups would suggest a closer relationship between these two types of soft tissue sarcomas.
Laboratory Investigation 03/2005; 85(2):176-81. · 3.64 Impact Factor
-
Isabelle Hostein,
Marie Andraud-Fregeville,
Louis Guillou,
Marie-José Terrier-Lacombe,
Colette Deminière, Dominique Ranchère,
Catherine Lussan,
Elisabeth Longavenne,
Nguyen Binh Bui,
Olivier Delattre,
Jean-Michel Coindre
[show abstract]
[hide abstract]
ABSTRACT: Identification of the alveolar subtype of rhabdomyosarcoma (ARMS) is important, because the poor prognosis associated with this subtype necessitates a modified therapeutic regimen. At present, ARMS diagnoses are made on the basis of histologic findings and the extent of myogenin immunopositivity. Nonetheless, the absence of an alveolar pattern in the solid variant, the low degree of differentiation in certain embryonal rhabdomyosarcomas (ERMS), and the increasing use of microbiopsy samples make the diagnosis of ARMS somewhat difficult. Two specific translocations have been found in ARMS, and fusion transcripts can be detected by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of paraffin-embedded tissue (PET).
To assess the value of myogenin staining and molecular testing in the diagnosis of rhabdomyosarcoma, the authors examined 109 rhabdomyosarcoma samples (45 ARMS samples and 64 ERMS samples). Real-time RT-PCR analysis of PET was performed in all 109 rhabdomyosarcomas, and RT-PCR analysis of frozen material was performed in 24 cases.
PAX fusion transcripts were present in 44 cases (39 ARMS and 5 ERMS) and absent in 52 cases (2 ARMS and 50 ERMS). In 13 cases (4 ARMS and 9 ERMS), the results were not interpretable. Results were concordant between paired frozen and fixed tumor samples. All 35 interpretable ERMS samples that contained < 50% myogenin-positive cells failed to yield detectable PAX fusion transcripts. Of the 61 interpretable tumor samples (41 ARMS and 20 ERMS) that contained > 50% myogenin-positive cells, 44 (39 ARMS and 5 ERMS) yielded detectable PAX fusion transcripts.
The current study demonstrates that molecular detection of PAX fusion transcripts via real-time RT-PCR analysis of PET is a sensitive and specific method for the diagnosis of ARMS and that immunohistochemical analysis of myogenin expression can be used to select cases for such molecular testing. Although RT-PCR analysis appears not to possess diagnostic value in tumors with < 50% tumor cell immunopositivity, it is strongly recommended for the diagnosis of tumors containing > 50% myogenin-positive cells.
Cancer 12/2004; 101(12):2817-24. · 4.77 Impact Factor
-
Cancer treatment and research 02/2004; 120:151-67.
-
[show abstract]
[hide abstract]
ABSTRACT: Ecteinascidin-743 (ET-743) is a natural product derived from the marine tunicate Ectenascidia turbinate. ET-743 binds in the minor groove of DNA, blocks transcription factors activity, and traps protein from the nucleotide excision repair system, thus blocking cells in G2-M phase. ET-743 demonstrated cytotoxic activity at very low concentrations against sarcoma cell lines in pre-clinical studies. In several phase II clinical studies in patients with advanced sarcoma failing conventional doxorubicin- and ifosfamide-based chemotherapy, ET-743 delivered by continuous intravenous 24-hour infusion at a dose of 1,500 microg/m2 every 21 days yielded 8% overall response and 30%-40% stabilization rates for a clinical benefit rate close to 40%. Interestingly, long-term stabilizations over more than 3 years have been described. In vivo, ET-743 has a specific toxicity profile, the major toxicity of this product being hepatic, through biliary duct destruction, and hematologic. ET-743 has also been evaluated in first-line treatment for these patients. Finally, due to its original mode of action and the lack of cross-resistance with other chemotherapy agents, ET-743 was tested in a preclinical model in combination with other drugs. Synergy was reported in vitro with doxorubicin and cisplatin; phase I combination studies are in progress.
The Oncologist 10(10):827-32. · 3.91 Impact Factor
