Bexarotene improves median survival (MS) in untreated, advanced NSCLC, when given in combination with carboplatin/paclitaxel

Document Type

Article

Department

Haematology and Oncology, East Africa

Abstract

Background: Bexarotene (bex) is a subclass specific, synthetic rexinoid analogue, that preferentially binds and modulates the expression of RXR subclass of receptors α, β, and γ. It induces concentration-dependent repression of multiple genes (cyclin D1/D3, total EGFR, pEGFR) inhibiting cell growth, angiogenesis, invasion and metastasis, inducing differentiation, and apoptosis in tumor cells. Several phase-I/II trials suggested increased survival in patients with advanced NSCLC.

Methods: Stage-IIIB with pleural effusion & Stage-IV chemo-naïve patients, ECOG 0–2, were enrolled and treated with carboplatin IV AUC-6 d-1 and paclitaxel IV 100 mg/m2 d-1, 8, 15, every 28-d for 4 cycles. Pts were randomized using a 1:1 design to bex PO 400 mg/m2/d either concurrent (C) from Day 1 or sequential (S) at the completion of chemo, for up to a year.

Results: 56 patients were enrolled; median age 62.3 (range 41–86), 48 TNM Stage IV, 38 males, 50 ECOG PS 0–1. Of 51 pts evaluable for response, 30 (58%) achieved PR (C: 15 and S: 15); 16 (31%) showed SD (C: 8 and S: 8), and 5 (9.5%) had PD (C: 3 and S: 2). Thirty-two (63%) patients have expired as of 12/31/05. Based on ITT, 40 evaluable pts showed a median TTP of 169 days (C: 166.5 and S 172); The MS for the entire group is 342 days (11.42 mo (C: 12.8 and S: 10.53). Currently, 10 pts are still alive between 407 to 1036 days from registration on the trial. The treatment was well tolerated; overall, AEs were reported in 48% of pts in the S arm and 51% in the C arm. The incidence of Gr 3–4 AEs, regardless of the treatment arm, was < 5%. There were no treatment-associated deaths.

Conclusions: Our data suggests a better ORR, TTP, and improvement in MS, when bex is added to carboplatin/ paclitaxel, regardless of concurrent or sequential administration, compared with chemo alone. ORR was not compromised by bex administration and in fact it was above average reported for similar phase-II & -III studies. Toxicity is easily managed.

Comments

This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

Journal of Clinical Oncology

DOI

https://doi.org/10.1200/jco.2006.24.18_suppl.17070

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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