چکیده
Background: To assess the response and the impact on the overall survival (OS) on c-KIT-positive (CD117+) gastrointestinal stromal tumours (GISTs) patients treated with imatinib mesylate.
Methods: Between July 2003 and December 2012, consenting patients with advanced c-kit-positive GISTs were enrolled to receive imatinib mesylate therapy at a dose of 400mg – 800mg daily, supplied gratis by Novartis Pharma (Basel, Switzerland) under its GIPAP initiative. Disease severity was based on tumour site, size and mitotic index at diagnosis. Clinical features together with drug toxicity, haematological and biochemical parameters were monitored. Overall survival (OS) reviewed at 12 months intervals over 5 years was computed using Kaplan-Meier
Results: There were 27 patients in all (17 males and 10 females with a median age of 52 years (range 26 - 83). Twenty three patients, 15 males and 8 females that have been followed up for at least 6 months were evaluated, aged 26 - 83 years (median = 56). There were 17 (73.9%) gastric tumours and 6 extragastric including 3 cases of peritoneum and 1 each of small gut, colon and rectum. At diagnosis, 21 (91.3%) cases were high risk, and 1 each fell into the intermediate and low risks, respectively. Ten patients (43.4%) including 5 with metastases presented with unresectable lesions. Five patients (21.7%) had complete tumour resection, 5 (3 with metastases) had partial resections and 3 others with non-bulky, non-metastatic diseases underwent no surgery. Imatinib was used as the primary therapy for all patients, except the 5 patients that underwent complete tumour resection. Nine (39.1%) patients were lost to disease progression with a median survival of 16.7 ± 10.7 (±SE) (95% CI = 0-37.6) months. The overall survival at 2 years for all patients was 71.9%, which dropped to 65.9% at 4 years.
Conclusions: Although a small number of GISTs, imatinib induced an extended remission in patients with advanced disease, most of whom would have been dead within a few months of diagnosis.
Keywords: Gastrointestinal stromal tumor, Imatinib, survival, surgery, Nigeria,
Résumé3450
Contexte: Afin d’évaluer la réponse et l’impact sur tous les survivants des patients de tumeurs gastro-intestinales cKIT-positif (CD117 +) puis traités par l’imatinib mésylate.
Méthodes: Entre Juillet 2003 et Décembre 2012, des patients consentants patients sérieusement atteints de c-kit positif ont été admis afin d’être traités par l’imatinib mésylate à la dose de 400 mg - 800 mg par jour, fourni gratuitement par Novartis Pharma (Bâle, Suisse) grâce à son initiative GIPAP. La gravité de la maladie était basée sur le la localisation de la tumeur, sa taille et l’index mitotique au moment du diagnostic. Les caractéristiques médicales ainsi que la toxicité des médicaments, les paramètres hématologiques et biochimiques ont été suivis. Les statistiques de la survie globale (OS) examinée a été faites à l’aide Kaplan Meier à 12 mois d’intervalle sur une période de 5 ans
Résultats: Il y avait au total 27 patients (17 hommes et 10 femmes âgés de 52 ans (tranche d’âge : 26-83). Vingt trois (23) patients dont 15 hommes et 8 femmes qui ont été suivis pendant au moins 6 mois, ont été évalués, âgés de 26 - 83 (âge moyen = 56). Il y avait 17 patients (73,9%) souffrant de tumeurs gastriques dont 6 extra- gastrique y compris 3 cas de péritoine et chacun de petit intestin grêle, du côlon et du rectum. Au moment du diagnostic, 21 cas (91,3%) étaient élevé, et chacun soit dans les risques moyen et faibles, respectivement. Dix patients (43,4%) dont 5 présentant les cas de métastases avec des lésions non résumables. Cinq patients (21,7%) ont eu une résection complète de la tumeur, (3 avec le métastases) ont eu des résections partielles et 3 autres avec des maladies non volumineux, non métastatiques n’ont subi aucune intervention chirurgicale. L’imatinib a été utilisé comme traitement de premier soin à tous les patients, sauf les 5 patients qui ont subi une résection complète de la tumeur. Neuf patients (39,1%) ont rendu l’âme au cours du processus de l’évolution de la maladie avec en moyenne 16,7 ± 10,7 (± SE) (IC à 95% = 0 à 37,6) survie au cours des mois. La survie globale de tous les patients à 2 ans était de 71,9%, puis chuté à 65,9% à 4ans.
Conclusions: Bien qu’un petit nombre de GIST, d’imatinib induise une rémission prolongée chez les patients atteints de graves maladies, la plupart mourait quelques mois après le diagnostic.
C-kit is a polyclonal antibody for identification of type III tyrosine kinase KIT that is expressed by most cases of GIST using immunohistochemical technque. CD117 is a KIT receptor antibody and it is used interchangeably with c-kit.
Correspondence: Prof. M.A. Durosinmi, Department of Haematology, Obafemi Awolowo University, Ile Ife, Nigeria. Email: mdurosin@gmail.com
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