A phase 2 study of dasatinib in recurrent clear cell carcinoma of the ovary, fallopian tube, peritoneum or endometrium: NRG oncology/gynecologic oncology group study 0283.

OBJECTIVE: Gynecologic cancers are traditionally managed according to their presumed site of origin, without regard to the underlying histologic subtype. Clear cell histology is associated with chemotherapy refractoriness and poor survival. Mutations in SWI/SNF chromatin remodeling complex member ARID1A, which encodes for BAF250a protein, are common in clear cell and endometriosis-associated endometrioid carcinomas. High-throughput cell-based drug screening predicted activity of dasatinib, a tyrosine kinase inhibitor, in ARID1A-mutant clear cell carcinoma. METHODS: We conducted a phase 2 clinical trial of dasatinib 140 mg once daily by mouth in patients with recurrent or persistent ovarian and endometrial clear cell carcinoma. Patients with measurable disease were enrolled and then assigned to biomarker-defined populations based on BAF250a immunohistochemistry. The translational endpoints included broad next-generation sequencing to assess concordance of protein expression and treatment outcomes. RESULTS: Twenty-eight patients, 15 of whom had tumors with retained BAF250a and 13 with loss of BAF250a were evaluable for treatment response and safety. The most common grade 3 adverse events were anemia, fatigue, dyspnea, hyponatremia, pleural effusion, and vomiting. One patient had a partial response, eight (28%) had stable disease, and 15 (53.6%) had disease progression. Twenty-three patients had next-generation sequencing results; 13 had a pathogenic ARID1A alteration. PIK3CA mutations were more prevalent in ARID1A-mutant tumors, while TP53 mutations were more prevalent in ARID1A wild-type tumors. CONCLUSIONS: Dasatinib was not an effective single-agent treatment for recurrent or persistent ovarian and endometrial clear cell carcinoma. Studies are urgently needed for this rare gynecologic subtype.

Evaluation of octylcyanoacrylate for wound repair of clinical circumcision and human skin incisional healing in a nude rat model.

PURPOSE: Alternative methods of circumcision wound closure have been studied to decrease repair time and complications, and improve cosmesis. This study includes a clinical and a laboratory research portion. Clinical parameters, wound outcome, closure time and operative time were compared for octylcyanoacrylate and suture approximation of circumcision incisions. An in vivo incisional model using human foreskin was used to compare the wound breaking strength of octylcyanoacrylate and suture repair. MATERIALS AND METHODS: Circumcision incisions were closed with suture or octylcyanoacrylate. Wound closure time and operating room time were recorded. Patients were evaluated 1 and 12 weeks postoperatively. Foreskin samples from another group of patients were engrafted to an immunodeficient rat and allowed to heal. Incisions were made in the human skin and the wounds were repaired with sutures or octylcyanoacrylate. After 7 days breaking stress was tested and healing was evaluated by histological testing. RESULTS: Optimal wound healing was noted in all patients 1 week after surgery. Scarring was absent in the octylcyanoacrylate group. Octylcyanoacrylate closure time was significantly shorter than suture time (p <0.001). Mean total operating room time for octylcyanoacrylate plus or minus standard deviation was shorter than for suture (19.4 +/- 0.51 versus 26.9 +/- 0.94 minutes, p <0.001). Octylcyanoacrylate wound breaking stress was equivalent to suture on tensiometry. Histological testing revealed normal healing in all wounds. CONCLUSIONS: Circumcision wounds may be closed by octylcyanoacrylate with shorter wound closure and operative time than by suture. In an animal model of human skin healing, wound breaking stress after octylcyanoacrylate closure was equivalent to suture repair. Octylcyanoacrylate may be a useful alternative to suture closure for circumcision incisions.