D Cupissol

Institut du Cancer de Montpellier Val d'Aurelle, Montpelhièr, Languedoc-Roussillon, France

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Publications (112)590.1 Total impact

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    ABSTRACT: Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (HNSCC) progressing after first-line platinum regimens have a poor prognosis and few treatment options. Afatinib, an irreversible ERBB family blocker, has shown efficacy in a phase 2 study in this setting. We aimed to assess the efficacy and safety of afatinib compared with methotrexate as second-line treatment in patients with recurrent or metastatic HNSCC progressing on or after platinum-based therapy. In this open-label, phase 3, randomised controlled trial conducted in 101 centres in 19 countries, we enrolled patients aged 18 years or older with histologically or cytologically confirmed HNSCC that was recurrent, metastatic, or both who had progressed on or after first-line platinum-based therapy, were not amenable for salvage surgery or radiotherapy, and who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Previous treatment with more than one systemic regimen in this setting was not allowed; previous treatment with EGFR-targeted antibody therapy (but not EGFR-targeted tyrosine-kinase inhibitors) was allowed. We randomly assigned eligible patients in a 2:1 ratio to receive oral afatinib (40 mg/day) or intravenous methotrexate (40 mg/m(2) per week), stratified by ECOG performance status and previous EGFR-targeted antibody therapy for recurrent or metastatic disease. Randomisation was done centrally with an interactive voice or web-based response system. Clinicians and patients were not masked to treatment allocation; independent review of tumour response was done in a blinded manner. The primary endpoint was progression-free survival as assessed by an independent, central imaging review committee. Efficacy analyses were done in the intention-to-treat population and safety analyses were done in patients who received at least one dose of study drug. This ongoing study is registered with ClinicalTrials.gov, number NCT01345682. Between Jan 10, 2012, and Dec 12, 2013, we enrolled 483 patients and randomly assigned 322 to afatinib and 161 to methotrexate. After a median follow-up of 6·7 months (IQR 3·1-9·0), progression-free survival was longer in the afatinib group than in the methotrexate group (median 2·6 months [95% CI 2·0-2·7] for the afatinib group vs 1·7 months [1·5-2·4] for the methotrexate group; hazard ratio [HR] 0·80 [95% CI 0·65-0·98], p=0·030). The most frequent grade 3 or 4 drug-related adverse events were rash or acne (31 [10%] of 320 patients in the afatinib group vs none of 160 patients in the methotrexate group), diarrhoea (30 [9%] vs three [2%]), stomatitis (20 [6%] vs 13 [8%]), fatigue (18 [6%] vs five [3%]), and neutropenia (1 [<1%] vs 11 [7%]); serious adverse events occurred in 44 (14%) of afatinib-treated patients and 18 (11%) of methotrexate-treated patients. Afatinib was associated with significant improvements in progression-free survival and had a manageable safety profile. These findings provide important new insights into the treatment of this patient population and support further investigations with irreversible ERBB family blockers in HNSCC. Boehringer Ingelheim. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet Oncology 04/2015; 16(5). DOI:10.1016/S1470-2045(15)70124-5 · 24.73 Impact Factor
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    ABSTRACT: Ombrabulin (AVE8062) disrupts the vasculature of established tumours and has shown preclinical synergistic anti-tumour activity when combined with cisplatin. In this phase 3 trial, we aimed to assess the efficacy and safety of ombrabulin plus cisplatin compared with placebo plus cisplatin in patients with advanced soft-tissue sarcomas. We did this multinational, randomised, double-blind, placebo-controlled phase 3 study at 44 centres in ten countries. Patients aged 18 years and older with metastatic soft-tissue sarcomas, an Eastern Cooperative Oncology Group performance status of 0-2, and who had previously received treatment with anthracycline and ifosfamide were randomly assigned (1:1) to intravenous infusion of ombrabulin 25 mg/m(2) plus cisplatin 75 mg/m(2) or intravenous infusion of placebo plus cisplatin 75 mg/m(2) every 3 weeks. Patients were allocated to treatment using a permuted blocks randomisation scheme (block size of four) via an interactive voice-response system, and stratified by histological subtype. Patients, medical staff, study investigators, and individuals who handled and analysed the data were masked to treatment assignment. Our primary endpoint was median progression-free survival in the intention-to-treat population. Safety analyses were done on all randomised patients who received at least one dose of study drug. This trial is now closed, and is registered with ClinicalTrials.gov, number NCT00699517. Between June 13, 2008, and April 26, 2012, we randomly assigned 355 patients to ombrabulin plus cisplatin (n=176) or placebo plus cisplatin (n=179). Median duration of follow-up was 27·9 (IQR 20·9-33·2) in the placebo group and 30·5 months (20·7-37·6) in the ombrabulin group. Progression-free survival was slightly, but significantly, improved in the ombrabulin group compared with the placebo group (median 1·54 months [95% CI 1·45-2·69] vs 1·41 [1·38-1·58] months; hazard ratio 0·76 [95% CI 0·59-0·98]; p=0·0302). Grade 3 or 4 adverse events occurred more frequently in individuals in the ombrabulin group than in those in the placebo group and included neutropenia (34 [19%] in the ombrabulin group vs 14 [8%] in the placebo group) and thrombocytopenia (15 [8%] vs six [3%] for placebo). Adverse events leading to death occurred in 18 patients in the ombrabulin group and 10 patients in the placebo group. The combination of ombrabulin and cisplatin significantly improved progression-free survival; however, it did not show a sufficient clinical benefit in patients with advanced soft-tissue sarcomas to support its use as a therapeutic option. Predictive biomarkers are needed for the rational clinical development of tumour vascular-disrupting drugs for soft-tissue sarcomas. Sanofi. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet Oncology 04/2015; 16(5). DOI:10.1016/S1470-2045(15)70102-6 · 24.73 Impact Factor
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    ABSTRACT: Metastatic leiomyosarcomas of uterine or soft-tissue origin have poor prognosis and moderate chemosensitivity. Trabectedin has shown activity in pretreated leiomyosarcoma. We did a single-group, multicentre, phase 2 trial (LMS-02) to assess the effect of first-line doxorubicin and trabectedin combination on disease control and survival. Adults (18 years to physiological age ≤70 years) with measurable metastatic or unresectable uterine leiomyosarcoma or soft-tissue leiomyosarcoma who had not received any previous chemotherapy were enrolled at 19 centres in France. Treatment consisted of 60 mg/m(2) intravenous doxorubicin followed by 1·1 mg/m(2) trabectedin in a 3 h intravenous infusion on day 1, both by the central venous route, and 6 mg subcutaneous pegfilgrastim on day 2, repeated every 3 weeks for up to six cycles. Surgery for residual disease was permitted. The primary endpoint was the proportion of patients achieving disease control, defined as complete or partial response or stable disease. Stratification was done by anatomical site and analyses were per protocol. This study is registered with ClinicalTrials.gov, number NCT02131480. Between July 28, 2010, and May 10, 2013, 109 patients were enrolled and treated, of whom 108 were assessable for response: 47 in the uterine leiomyosarcoma group and 61 in the soft-tissue leiomyosarcoma group. 32 (68%) patients in the uterine leiomyosarcoma group and 45 (74%) in the soft-tissue leiomyosarcoma group received all six cycles of treatment. Of 47 patients with uterine leiomyosarcoma, 28 (59·6%, 95% CI 44·3-73·6) achieved a partial response and 13 (27·7%, 15·6-42·6) stable disease; 41 (87·2%, 74·3-95·2) patients achieved disease control. Of 61 patients with soft-tissue leiomyosarcoma, two (3·3%, 95% CI 0·4-11·7) achieved a complete response, 22 (36·1%, 25·0-50·8) had a partial response, and 32 (52·5%, 40·8-67·3) had stable disease; 56 (91·8%, 81·9-97·3) of patients achieved disease control. The most common grade 3-4 treatment-associated adverse events were neutropenia (84 [78%] of 108 patients), increased alanine aminotransferase concentration (42 [39%]), thrombocytopenia (40 [37%]), anaemia (29 [27%]), febrile neutropenia (26 [24%]), and fatigue (21 [19%]). Despite expected but manageable toxic effects, these results support the activity of doxorubicin plus trabectedin as first-line treatment for uterine leiomyosarcoma and soft-tissue leiomyosarcoma. This combination should be developed further in a phase 3 trial against the present standard of care. Pharmamar and Amgen. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet Oncology 03/2015; 16(4). DOI:10.1016/S1470-2045(15)70070-7 · 24.73 Impact Factor
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    ABSTRACT: The mainstay of first line treatment in metastatic sarcomas is chemotherapy with response rates of ≈25% but the optimal management of further events is debated. We assessed the benefit of local metastatic treatment in metastatic sarcomas.
    Critical Reviews in Oncology/Hematology 01/2015; DOI:10.1016/j.critrevonc.2015.01.004 · 4.05 Impact Factor
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    ABSTRACT: Few targeted therapies (TTs) are registered for sarcoma treatment despite numerous phase II studies and yet there are potential treatment options for patients after standard treatment escape. The French Sarcoma Group - Bone Tumor Study Group (GSF-GETO) created a national registry to evaluate the outcome of patients treated with off-label TTs. Every consecutive sarcoma-patient receiving an off-label TT outside a clinical trial was included. The objective was to describe this patient efficacy and safety data in routine practice. From October 2008 to October 2011, 249 patients in 24 centers received 278 treatment lines with TTs. Twenty-five histological subtypes were included: most frequent were leiomyosarcoma (n =48, receiving sorafenib in 63%, and sunitinib in 27%), GIST (n =39, receiving sorafenib in 79%), and angiosarcoma (n =18, receiving sorafenib in 78%). The overall response rate to TTs was 15% (95%CI [10,6-20,2]), the disease control rate at 2 months was 59%. The median progression-free survival was 4,1 months (IC95% [3,2-4,8]). Three complete responses were observed. No toxic death occurred, grade 3 and 4 toxicities were reported in 74 (27%) and 14 patients (5%) respectively. Off-label TTs can be used for sarcoma patients in routine practice with an acceptable toxicity profile and efficacy similar to that reported in non-randomized clinical trials.
    BMC Cancer 11/2014; 14(1):870. DOI:10.1186/1471-2407-14-870 · 3.32 Impact Factor
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    ABSTRACT: Introduction. - The management of metastatic cutaneous melanoma is changing, marked by innovative therapies. However, their respective use and place in the therapeutic strategy continue to be debated by healthcare professionals. Objective. - The French national cancer institute has led a national clinical practice guideline project since 2008. It has carried out a review of these modalities of treatment and established recommendations. Methods. - The clinical practice guidelines development process is based on systematic literature review and critical appraisal by experts. The recommendations are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines are reviewed by independent practitioners in cancer care delivery. Results. -This article presents the results of bibliographic search, the conclusions of the literature and the recommendations concerning locoregional treatments of brain metastases for patients with metastatic cutaneous melanoma. (C) 2014 Published by Elsevier Masson SAS.
    Neurochirurgie 09/2014; 60(6). DOI:10.1016/j.neuchi.2014.05.002 · 0.47 Impact Factor
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    ABSTRACT: Afatinib is an oral, irreversible ErbB family blocker that has shown activity in epidermal growth factor receptor (EGFR)-mutated lung cancer. We hypothesized that the agent would have greater anti-tumor activity compared to cetuximab in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients, whose disease has progressed after platinum-containing therapy.
    Annals of Oncology 06/2014; 25(9). DOI:10.1093/annonc/mdu216 · 6.58 Impact Factor
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    Annales de Dermatologie et de Vénéréologie 05/2014; 141(5):404–405. DOI:10.1016/j.annder.2014.04.204 · 0.67 Impact Factor
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    ABSTRACT: Rectal and pararectal gastrointestinal stromal tumors (GISTs) are rare. The optimal management strategy for primary localized GISTs remains poorly defined. We conducted a retrospective analysis of 41 patients with localized rectal or pararectal GISTs treated between 1991 and 2011 in 13 French Sarcoma Group centers. Of 12 patients who received preoperative imatinib therapy for a median duration of 7 (2-12) months, 8 experienced a partial response, 3 had stable disease, and 1 had a complete response. Thirty and 11 patients underwent function-sparing conservative surgery and abdominoperineal resection, respectively. Tumor resections were mostly R0 and R1 in 35 patients. Tumor rupture occurred in 12 patients. Eleven patients received postoperative imatinib with a median follow-up of 59 (2.4-186) months. The median time to disease relapse was 36 (9.8-62) months. The 5-year overall survival rate was 86.5%. Twenty patients developed local recurrence after surgery alone, two developed recurrence after resection combined with preoperative and/or postoperative imatinib, and eight developed metastases. In univariate analysis, the mitotic index (<=5) and tumor size (<=5 cm) were associated with a significantly decreased risk of local relapse. Perioperative imatinib was associated with a significantly reduced risk of overall relapse and local relapse. Perioperative imatinib therapy was associated with improved disease-free survival. Preoperative imatinib was effective. Tumor shrinkage has a clear benefit for local excision in terms of feasibility and function preservation. Given the complexity of rectal GISTs, referral of patients with this rare disease to expert centers to undergo a multidisciplinary approach is recommended.
    BMC Cancer 03/2014; 14(1):156. DOI:10.1186/1471-2407-14-156 · 3.32 Impact Factor
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    ABSTRACT: Metastases are responsible for the majority of deaths from solid cancers. Metastatic phenomenon, complex, is a multi-step process where interactions between cells and with the microenvironment are essential. The organ tropism, that is the propensity of a cancer to metastasize to specific organs, can be explained by several mechanisms that we have described. Apart from the usual metastases, unusual sites can appear with heterogeneous clinical presentations. We describe known to date mechanisms that can explain these unusual metastasis. A summary of these locations has been realized. A rare location should always be considered in front of any atypical symptom.
    Bulletin du cancer 02/2014; 101(2). DOI:10.1684/bdc.2014.1889 · 0.64 Impact Factor
  • Revue d Épidémiologie et de Santé Publique 02/2014; 62:S5. DOI:10.1016/j.respe.2013.11.003 · 0.66 Impact Factor
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    ABSTRACT: Recent years have seen the emergence of new molecules for the treatment of patients with metastatic cutaneous melanoma, with significant benefits in terms of survival and the opening of new therapeutic perspectives. In addition, many techniques are currently being developed for locoregional treatment of metastatic sites. Management of metastatic melanoma is thus fast-changing and is marked by innovative therapeutic approaches. However, the availability of these new treatments has prompted debate among healthcare professionals concerning their use and their place in therapeutic strategy. Since 2008, the French National Cancer Institute (INCa) has been leading a project to define and diffuse national clinical practice guidelines. It has performed a review of these treatment methods, which it aims to circulate, and it is seeking to develop recommendations in order to allow nationwide implementation of innovative approaches while promoting good use thereof. The clinical practice guidelines development process is based on systematic literature review and critical appraisal by experts within a multidisciplinary working group, with feedback from specialists in cancer care delivery. The recommendations are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines are reviewed by independent practitioners in cancer care delivery. This article presents the national recommendations for first- and second-line systemic treatment and for locoregional treatment of metastatic sites in patients presenting metastatic cutaneous melanoma.
    Annales de Dermatologie et de Vénéréologie 02/2014; 141(2):111-21. DOI:10.1016/j.annder.2013.10.055 · 0.67 Impact Factor
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    ABSTRACT: la mise à disposition récente de nouvelles molécules pour le traitement du mélanome cutané métastatique avec un bénéfice significatif sur la survie des patients soulève auprès des professionnels de santé des interrogations quant à leur utilisation et place dans la stratégie thérapeutique.l’Institut national du cancer (INCa), dont l’une des missions est de définir et de favoriser la diffusion de recommandations nationales de bonnes pratiques cliniques depuis 2008, a souhaité diffuser un état des lieux des connaissances sur ces nouvelles modalités de traitement et formuler des recommandations afin de permettre une diffusion au niveau national de l’innovation tout en favorisant son bon usage.le processus d’élaboration est basé sur une revue systématique de la littérature et sur le jugement argumenté d’experts cliniciens au sein d’un groupe de travail multidisciplinaire. Avant publication, les recommandations sont revues par des experts cliniciens indépendants du groupe de travail.cet article présente les recommandations nationales relatives au traitement systémique de 1ère et de 2ème ligne des patients atteints d’un mélanome cutané métastatique (hors métastase cérébrale).
    Oncologie 02/2014; 16. DOI:10.1007/s10269-013-2360-4 · 0.08 Impact Factor
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    ABSTRACT: the last years are marked by the emergence of new molecules for the treatment of metastatic cutaneous melanoma with a significant benefit on the survival. Besides, some techniques are in development for the loco-regional treatment of the metastatic sites, bringing new therapeutic perspectives. However, their respective use and place in the therapeutic strategy are debated by healthcare professionals. the French National Cancer Institute leads a national clinical practice guidelines project since 2008. It realized a review of these modalities of treatment and developed recommendations. the clinical practice guidelines development process is based on systematic literature review and critical appraisal by a multidisciplinary expert workgroup. The recommendations are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines are reviewed by independent practitioners in cancer care delivery. this article presents recommendations for loco-regional treatments of the pulmonary, bone, cutaneous, hepatic and digestive metastatic sites for patients with pauci-metastatic cutaneous melanoma.
    Bulletin du cancer 12/2013; 101(1). DOI:10.1684/bdc.2013.1868 · 0.64 Impact Factor
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    ABSTRACT: As a consequence of under-representation of elderly patients in clinical trials, the recommended dose of chemotherapy is often based on results observed in younger patients. We designed a risk-adapted, dose escalation study of weekly docetaxel in the first-line treatment of elderly patients with cancer in order to determine the optimal dose according to age, comorbidity and functional status. Sixty-eight patients aged 70 or more were stratified into three risk groups according to a combination of age, performance status, and comorbidity. The study was conducted using a standard phase I design with sequential cohorts of patients receiving docetaxel at increasing doses in each risk group. The maximum tolerated dose was not reached in the intermediate-risk group and was 45mg/m(2)/week in the high-risk group. Because of a slow recruitment rate, it was not possible to conclude the trial in the good-risk category. Neutropenia, asthenia and diarrhea were the most frequently encountered severe toxicities. Docetaxel can be used at a dose of 40mg/m(2)/week as a first-line treatment for elderly patients with locally advanced or metastatic cancer without excessive toxicity. The risk groups defined in the study are not able to accurately distinguish between subgroups of patients with divergent toxicity profiles.
    Journal of Geriatric Oncology 04/2013; 4(2):122-7. DOI:10.1016/j.jgo.2012.11.002 · 1.15 Impact Factor
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    ABSTRACT: OBJECTIVE: Worldwide, head and neck carcinomas account for 5% of all malignancies. Two-thirds of patients relapse after initial multimodal therapy. Until early 2000, the median overall survival (OS) of metastatic patients was about 6months. Recently, new drugs have been incorporated in patient management, thus enabling an increase in OS. This review aims to define the comprehensive medical management of patients with relapsing head and neck carcinoma. METHODS: A comprehensive review of the literature was made targeting four topics: first- and second-line treatment, supportive care, and management of elderly patients. RESULTS: The choice of first- or second-line treatments is mainly based on performance status. In the elderly, geriatric assessment could be helpful. For PS 0.1 patients, the standard first-line treatment is 6cycles of cisplatin-5FU-cetuximab. In the event of response, cetuximab alone is prolonged until progression or unacceptable toxicity. For second-line treatment, several options are currently available: enrolment in clinical trials, single-agent therapy (methotrexate, taxane, cetuximab), and best supportive care (BSC). Supportive care has to be initiated very early in the course of the disease to prevent pain, dysphagia and malnutrition. In elderly patients, the therapeutic options are: first-line treatment with the EXTREME regimen replacing cisplatin by carboplatin for patients in good general condition or methotrexate alone for other patients. BSC continues to be given to all patients (i.e. poor general conditions). CONCLUSION: In spite of numerous pending issues requiring further investigation, these recommendations seem to be routinely applicable.
    Oral Oncology 02/2013; 49(6). DOI:10.1016/j.oraloncology.2013.01.005 · 3.03 Impact Factor
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    ABSTRACT: Background We previously demonstrated that interruption of imatinib mesylate (IM) in responding patients (pts) with advanced gastrointestinal stromal tumours (GISTs) results in rapid reprogression. The impact of interruption on residual tumour, quality of response and secondary resistance has not been fully investigated.Patients and methodsWithin the BRF14 study, 71 non-progressing patients were randomly assigned in the interruption arms after 1, 3 or 5 years. IM was resumed in the case of progressive disease (PD). Tumour status at randomisation, relapse and after IM rechallenge, progression-free survival (PFS) and time to secondary resistance were analysed.ResultsAt data cut-off, 51 of 71 patients had restarted IM following documented PD. Eighteen patients (35%) progressed on known lesions only, while 33 patients (65%) had new lesions, with concomitant progression of known lesions in 17 patients. Only 8 (42%) of complete remission (CR) patients and 12 (52%) of partial response (PR) patients at randomisation achieved a new CR and PR. Patients progressing rapidly after interruption had a poorer prognosis. Tumour status at randomisation influenced time to progression after rechallenge.Conclusion In advanced GIST patients interrupting IM, quality of response upon reintroduction did not reach the tumour status observed at randomisation. Rapid progression after imatinib interruption is associated with poor PFS after reintroduction.
    Annals of Oncology 11/2012; 24(4). DOI:10.1093/annonc/mds587 · 6.58 Impact Factor
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    ABSTRACT: BACKGROUND: Phase II trials demonstrate the activity of cisplatin in patients with refractory Ewing sarcoma family tumours (ESFT) and also the feasibility of giving cisplatin with oral VP16 in a variety of different cancers. This trial was conducted to evaluate the activity and toxicity profile of this combination delivered as outpatient therapy in patients with refractory/relapsed ESFT. METHODS: Cisplatin was administered on days 1, 8 and 15 and days 29, 36 and 43 (70 mg/m(2)/dose for patients <21 years of age and 50 mg/m(2)/dose ≥21 years). VP16 was administered at a dose of 50 mg/m(2) on days 1-15 and days 29-43 inclusive. A three-stage Fleming statistical design was used for analysis. RESULTS: Between January 2003 and October 2006, 45 patients aged between 5 and 46 years (median 19) were enrolled. Thirty-eight were evaluable for response. Patients had previously received one to three lines of chemotherapy (median = one). Seventy-three per cent of the patients had grade 3/4 neutropenia, 20 % developed fever, 40 % had grade 3/4 anaemia, 68 % grade 3/4 thrombocytopenia and 16 % grade 2/3 ototoxicity. Measured response after 2 cycles: 0 CR, 7 PR (18 %), 13 SD (34 %), 18 PD (48 %). There was excellent concordance between unidimensional and bidimensional criteria in 31 of 33 responses (94 %). PFS at 1 year was 39 %, with a median PFS of 6 months. Overall survival at 1 year was 44 %; median survival was 11 months. CONCLUSIONS: Cisplatin combined with oral VP16 is well tolerated and has acceptable side effects, but limited clinical activity in refractory/relapsed ESFT.
    Cancer Chemotherapy and Pharmacology 11/2012; DOI:10.1007/s00280-012-2015-7 · 2.57 Impact Factor
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    ABSTRACT: Background. This study aimed to evaluate the efficacy and toxicity of single-agent gemcitabine versus gemcitabine plus docetaxel as second-line therapy in patients with uterine and nonuterine leiomyosarcoma (LMS). Patients and Methods. Patients had metastatic or unresectable LMS and had received one prior anthracycline-based regimen. A total of 90 patients received either single-agent gemcitabine (arm A; gemcitabine, 1,000 mg/m(2) i.v. for 100 minutes on days 1, 8, and 15 of a 28-day cycle) or a combination of gemcitabine and docetaxel (arm B; gemcitabine, 900 mg/m(2) i.v. for 90 minutes on days 1 and 8, plus docetaxel, 100 mg/m(2) i.v. for 1 hour on day 8 of a 21-day cycle with lenograstim). The primary endpoint was the objective response rate. Results. The objective response rates were 19% and 24% in arm A (gemcitabine) and arm B (gemcitabine plus docetaxel), respectively, for patients with uterine LMS. For patients with nonuterine LMS, the objective response rates were 14% and 5% for arms A and B, respectively. The median progression-free survival times for arms A and B were 5.5 months and 4.7 months, respectively, for patients with uterine LMS. For patients with nonuterine LMS, the median progression-free survival times were 6.3 months and 3.8 months for arms A and B, respectively. One toxic death occurred in arm B. Conclusions. Both single-agent gemcitabine and gemcitabine plus docetaxel were found to be effective second-line therapies for leiomyosarcomas, with a 3-month progression-free survival rate of 40% for LMS with both uterine and nonuterine sites of origin. Single-agent gemcitabine yielded results similar to those of gemcitabine plus docetaxel in this trial, but patients using single-agent gemcitabine experienced less toxicity.
    The Oncologist 08/2012; 17(9):1213-20. DOI:10.1634/theoncologist.2011-0467 · 4.54 Impact Factor
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    ABSTRACT: Angiosarcomas account for <2% of all soft tissue sarcomas. This subtype is one of the most aggressive forms of soft tissue sarcoma. The prognosis for angiosarcoma patients in the advanced phase remains poor with current cytotoxic agents (progression-free survival [PFS] time of ∼4 months and overall survival [OS] time of ∼8 months). We investigated the antitumor activity of sorafenib in patients with metastatic or advanced angiosarcomas in a phase II trial. We conducted a stratified phase II trial. The primary endpoint was the progression-free rate (PFR) at 9 months according to the Response Evaluation Criteria in Solid Tumors. A two-stage design (optimal Simon design) was used. Patients received sorafenib (400 mg twice daily) for 9 months until unacceptable toxicity or tumor progression. Central pathological and radiological reviews were performed. Data on stratum A (superficial angiosarcoma) and stratum B (visceral angiosarcoma) are currently available. This trial is registered with ClinicalTrials.gov (identifier, NCT00874874). Strata A and B recruited 26 and 15 patients, respectively. The median age was 63 years (range, 31-82 years), with 17 male and 24 female patients. Fourteen cases arose in irradiated fields. Thirty patients (73.0%) had been pretreated with conventional chemotherapy. No unexpected toxicity occurred. The PFR at 9 months was 3.8% in stratum A and 0.0% in stratum B. The median PFS times were 1.8 months and 3.8 months, respectively, whereas the median OS times were 12.0 months and 9.0 months, respectively. No responses were observed in chemotherapy-naïve patients, whereas a 40% tumor control rate and 23% response rate were observed in the pretreated population. In this cohort, no activating mutation of the KDR gene (exons 15, 16, 24) was detected. Sorafenib showed limited antitumor activity in pretreated patients only, for both visceral and superficial angiosarcoma, but tumor control was of short duration.
    The Oncologist 02/2012; 17(2):260-6. DOI:10.1634/theoncologist.2011-0237 · 4.54 Impact Factor

Publication Stats

3k Citations
590.10 Total Impact Points

Institutions

  • 1989–2015
    • Institut du Cancer de Montpellier Val d'Aurelle
      • Department of Radiation Oncology
      Montpelhièr, Languedoc-Roussillon, France
  • 1993
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 1984
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France