Virtual Library
Start Your Search
S. Rosales
Author of
-
+
P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
-
+
P3.01-087 - A Phase I Study of Exemestane with Carboplatin and Pemetrexed in Postmenopausal Women with Metastatic, Non-Squamous Non-Small Cell Lung Cancer (ID 2171)
09:30 - 09:30 | Author(s): S. Rosales
- Abstract
Background:
Lung cancer is the most common cause of cancer-related deaths in the US, with adenocarcinoma being the most common histologic subtype. Aromatase, a critical rate-limiting enzyme in estrogen biosynthesis, is notably expressed in NSCLC cells. Retrospective studies show that high NSCLC aromatase levels are associated with worse clinical outcome, particularly in postmenopausal women (Weinberg et al., Cancer Res, 2005; Mah et al., Cancer Res, 2007; Garon et al., J Thoracic Oncol, 2013). Estrogens are known survival factors in lung and promote expression of nucleotide excision repair enzyme ERCC1 that is implicated in resistance to platinum-therapy. In NSCLC cells, ERCC1 transcript expression is blocked by exemestane, an aromatase inhibitor (AI), enhancing cisplatin-induced apoptosis. In preclinical NSCLC xenograft models, exemestane exerts synergistic antitumor activity combined with cisplatin and results in prolonged tumor suppression (Marquez-Garban et al., Ann NY Acad Sci, 2009). These data provide a rationale to assess an AI in the clinic.
Methods:
Based on our preclinical studies, we are conducting a phase IB, open-label, single-center study in postmenopausal, treatment-naïve (except prior single-agent tyrosine kinase inhibitor use) women with metastatic, non-squamous NSCLC (NCT 01664754). We plan to enroll 12-15 participants divided into two dose-escalation cohorts of exemestane. All participants receive standard chemotherapy with pemetrexed (500 mg/m[2]) and carboplatin (AUC 6), both given intravenously every 3 weeks. Cohort 1, which added exemestane 25 mg orally daily, has completed enrollment without any dose-limiting toxicities. Cohort 2, for which enrollment started in December of 2013, evaluates exemestane at 50 mg orally daily. Our primary aim is to evaluate safety and tolerability of the indicated regimen. Secondary objectives are tumor response rate, quality of life, pharmacokinetics/pharmacodynamics, and correlative studies of biomarkers (such as blood estrogens, tumor ERs, aromatase, and apoptosis) with tumor response.
Results:
Not applicable
Conclusion:
Not applicable
