Résumé
Only two drugs, doxorubicin and ifosfamide, have demonstrated consistent response rates greater than 15% in phase-II trials with more than 30 patients. The new century has clearly begun a challenging period that brings into question the concept of the clinical trial for locally advanced and metastatic soft tissue sarcoma (STM). New active drugs are urgently needed for the treatment of sarcoma, and one of the main goals of clinical trials that assess the activity of new agents in well-known, advanced chemoresistant tumours is to identify, in a small cohort, potentially active drugs by comparing them to agents previously determined to be inactive. Due to the heterogeneity of both the tumours and the patients participating in phase-II trials, results are often inconclusive and controversial. Different histological subtypes behave like different diseases, with varying chemosensitivity (liposarcoma vs leiomyosarcoma). Overall survival and the full or partial response to chemotherapy, therefore, cannot be predicted by the same factors, using retrospective analysis; consequently, response rates should not be the only end points in assessing new agents and drug combinations for sarcoma. In terms of objective response (WHO response criteria), which, today, defines the activity of chemotherapy and biotherapy, the results produced by new drugs have been disappointing. None of the following agents have achieved an objective response rate greater than 15% in palliative care situations: taxanes, liposomal doxorubicin, gemcitabine, topotecan, and ET-743. However, under closer analysis, these studies revealed significant activity in a number of histologically distinct sarcoma subtypes: gemcitabine in uterine leiomyosarcomas, ET-743 in leiomyosarcoma and myxoid liposarcoma, and paclitaxel in angiosarcoma. These new drugs have opened up a new era of specific drugs for selected sarcomas and the emergence of a new drug treatment concept for the disease. Imatinib's dramatic activity in advanced gastrointestinal stromal tumours (GIST) must change our strategic approach to managing patients with advanced sarcoma. The era of targeted therapy has began with the use of imatinib to treat GIST expressing a mutated tyrosine kinase receptor, and the discovery of other tumour targets, such as type-1 EGFR in synovialosarcoma, PDGFRB amplification in dermatofibrosarcoma protuberans and VEGFR amplification in many sarcomas targeted by antiangiogenic factors.
Titre traduit de la contribution | Chemotherapy for metastatic and locally advanced soft tissue sarcoma |
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langue originale | Français |
Pages (de - à) | 114-125 |
Nombre de pages | 12 |
journal | Oncologie |
Volume | 9 |
Numéro de publication | 2 |
Les DOIs | |
état | Publié - 1 mars 2007 |
mots-clés
- Advanced sarcoma
- Chemotherapy
- Targeted therapy