Publication | Closed Access
A phase II study of temsirolimus (CCI-779) in patients with metastatic and/or locally advanced recurrent endometrial cancer previously treated with chemotherapy: NCIC CTG IND 160b
53
Citations
0
References
2008
Year
Cancer ManagementGynecologyPathologyPhase Ii StudyMetronomic ChemotherapyPten LossGynecology OncologyTumor BiologyOncologyMetastatic And/orMetronomic TherapyRadiation OncologyMolecular OncologyCancer ResearchCancer TreatmentPten FunctionEndocrine-related CancerRecurrent Endometrial CancerMedicine
5516 Background: Loss of PTEN function occurs in 26–80% of endometrial carcinomas and leads to deregulated PI3K/Akt/mTOR signalling which may provide neoplastic cells with a selective survival advantage by enhancing angiogenesis, protein translation and cell cycle progression. Inhibition of mTOR with temsirolimus, an ester derivative of rapamycin, has demonstrated promising activity, irrespective of PTEN loss, in chemotherapy naïve endometrial cancer with an objective response rate of 21% and prolonged stable disease in 48%. This trial was designed to assess the level of activity in patients who had previously received chemotherapy. Methods: A single stage phase II study of temsirolimus in women with chemotherapy treated, recurrent or metastatic endometrial cancer has been completed, at a dose of 25mg i.v. weekly. 27 eligible patients have been enrolled and archival specimens of tumour have been collected for PTEN immunohistochemistry analysis. Thirteen had received prior radiation and 10 hormonal therapy. Twenty five patients had adenocarcinoma (8 serous carcinoma) and 2 had adeno-squamous carcinoma; 20 patients had grade 2/3 disease, 5 unknown and 2 grade 1. Results: Hematologic toxicity has been mild with 5 episodes of grade 3 lymphopenia and 2 of anemia; 8 patients had grade 3/4 non-hematologic adverse events [pneumonitis, mucositis, fatigue, GI, pain]. Grade 3/4 biochemical toxicities were hypokalemia, hyperglycemia, hypoalbuminemia and hypophosphatemia. Two patients have had a confirmed partial response (PR) (7.4%; 95% CI 0.9–24.3%) and 12 patients had stable disease (SD) (44%), median duration 3.5months (2.4–7.2m) and 10 patients had progressive disease (41.7%). Five of the 8 patients with serous disease had SD and of the 17 with Grade 3 disease, 1 was PR and 7 SD. PTEN assays are underway. Conclusions: The results indicate modest activity for Temsirolimus in women with recurrent endometrial cancer previously treated with chemotherapy. Supported by a grant from the National Cancer Institute of Canada with funds from the Canadian Cancer Society No significant financial relationships to disclose.