TITLE:
Primary Anorectal Melanomas Interest of Targeting C-KIT in Two Cases from a Series of 11 Patients
AUTHORS:
Karima Oualla, Nawfel Mellas, Fatimazahra El’mrabet, Samia Arifi, Afaf Amarti, Khalid Ait Taleb, Siham Tizniti, Omar Elmesbahi
KEYWORDS:
Melanoma; Anorectal Area; Surgery; Chemotherapy; C-KIT; Imatinib
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.5 No.3,
March
10,
2014
ABSTRACT: Background: The anorectal
location of melanomas is extremely rare (1% - 3%
of all melanomas), and the prognosis remains poor because of the aggressiveness
and the high metastatic potential of those tumors. The discovery that the KIT
oncogene may be aberrantly activated in a subset of patients with anorectal
melanoma creates a realm of possibility for the development of targeted
molecular therapy. Aim: to show the epidemiologic, clinico-radiological,
histological features and treatment management especially in patients with
over-expression of C-KIT treated by Imatinib. Methods: It is a retrospective
study conducted in the department of medical oncology at Hassan II University
Hospital between January 2007 and January 2012, including all patients with
histologically proven melanoma of the anorectal area. Results: 11 cases were
collected, with slight female predominance. Nine patients were metastatic at
the moment of diagnosis, and only two with local stage, but evolution was
marked by local and distant recurrence less than 12 months after abdo-minoperineal
resection. First line of chemotherapy was based mainly on paclitaxel,
carboplatine and dacarbazine. Response was modest with only 3 partial
responses, 4 patients with disease stability, and 4 patients with disease
progression. Two patients, with over expression of C-KIT, received Imatinib as
second line of treatment with significant improvement of symptoms and radiological
response reaching 50%. Seven patients died with a median survival of 11 months
from diagnosis to the date of death. Conclusion: Primary anorectal melanomas
are very rare, with high aggressiveness and poor prognosis. Treatment
management is still a big challenge given to the modest efficacy of
conventional chemotherapy. Better understanding of carcinogenesis and signaling
pathways will allow development of new targeted therapies.