Medical therapy of advanced malignant epithelial tumours of the ovary
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Notice bibliographique
Résumé
Despite improvements seen in median and overall survival using a combination of platinum-compounds and paclitaxel (PTX), long-term survival rates for patients with advanced epithelial ovarian carcinoma remain disappointing and ongoing efforts have aimed to develop more effective primary therapy. In the early 1990Os the drug PTX was first tested in ovarian cancer. In the Gynaecological Oncology Group (GOG) trial 111 the cisplatin (CP)+PTX regimen was judged to be superior compared to the platinum-based control arm with an improvement of overall response rate, median progression-free interval and overall median survival. These favourable data were confirmed by a European-Canadian Intergroup trial (OV10). In contrast, in a further GOG trial (GOG132) there was no difference in survival between CP alone and the combination of PTX and CP. The International Collaborative Ovarian Neoplasm Study (ICON)3 is the first and only trial comparing PTX plus carboplatin against carboplatin alone or a (non-taxane) CP-based control arm. The last analysis performed with a total of 1,293 events showed an estimated absolute difference in one-year progression-free survival of 1% and in two-year overall survival of 2% both in favour of PTX plus carboplatin. The results of ICON3, in accordance with GOG132 study, appear to contradict the earlier positive results seen for PTX and CP in the GOG-111 and OV10 trials and suggested that single agent carboplatin, CY-adriamycin-CP are safe and effective first-line treatments for women requiring chemotherapy for ovarian cancer. A meta-analysis with individual patient data is warranted to better clarify the issue of PTX in the front line therapy of advanced ovarian cancer. Salvage chemotherapy is often utilised in patients with advanced ovarian cancer, due to the high frequency of recurrent disease even after a clinical or pathological complete response after primary chemotherapy. Main objectives of salvage chemotherapy include: i. improvement in quality of life and symptoms; ii. tumour load reduction and survival advantage; iii. evaluation of potentially active new drugs to be included in first-line. Since the goal is palliation in most cases, monotherapy is generally indicated. However, the chances of response are directly related to the treatment-free interval, with a response rate nearly equivalent to that of primary chemotherapy when the treatment-free interval exceeds 24 months. Extension of the platinum-free interval before re-treatment with platinum or taxanes may allow partial reversal of resistance to these agents which can therefore still show significant activity in relapsing patients. Unfortunately, durable response to salvage chemotherapy is rare and cure is almost impossible. The sequential use of the agents currently available for salvage treatment in monotherapy may transform ovarian cancer into a chronic disease and confers long survival to the patients. Perhaps, the most interesting role of second-line chemotherapy is to identify new potentially active drugs, which can be moved up-front. Most of the compounds used in second line (gemcitabine, topotecan, liposomal doxorubicin) are in fact under investigation to develop alternative schedules and sequences of drug administration. A new phase III multi-national randomised study for patients with advanced stage epithelial ovarian or primary periperitoneal carcinoma will evaluate the impact of incorporating a new drug within either a platinum-based triplet (new drug + platinum + PTX) or a sequential-doublet (new drug + platinum followed by platinum + PTX) in order to identify one or more experimental regimens able to improve long-term survival with acceptable toxicity.
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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découle