B1-06: Multicenter, randomized study of docetaxel versus docetaxel plus oblimersen in patients previously treated for non-small cell lung cancer (NSCLC)

Document Type

Article

Department

Haematology and Oncology, East Africa

Abstract

Background: Bcl-2 protein is a fundamental cause of tumor cell ac- cumulation and resistance to anticancer therapy. Oblimersen (Genas- ense® ), a Bcl-2 antisense oligonucleotide, selectively targets bcl-2 RNA for degradation by RNase H and thus decreases Bcl-2 protein produc- tion. Oblimersen enhances the activity of anticancer agents (including docetaxel) in animal models, including NSCLC. Findings in clinical studies conducted in patients with various solid tumors and hemato- logic malignancies support this effect.

Methods: A multicenter, randomized study of docetaxel versus docetaxel plus oblimersen was conducted in patients with NSCLC who had received not more than 1 prior exposure to cytotoxic chemotherapy and had relapsed after or were refractory to that therapy. Patients were ≥ 18 years of age and had measurable disease (Stage IIIB or IV) not previously irradiated, ECOG performance status ≤ 2, adequate organ function, and a life expectancy ≥ 12 weeks. Key exclusion criteria were untreated or symptomatic brain metastases, peripheral neu- ropathy ≥ Grade 2, and prior radiation therapy to ≥ 25% of the bone marrow. Patients were stratified based on 3 factors (response to prior chemotherapy, ECOG performance status [0 or 1 versus 2], and prior paclitaxel treatment [yes versus no]) and then centrally randomized at a 1:1 ratio. Patients received docetaxel 75 mg/m2 on Day 1 by IV infu- sion or oblimersen 7 mg/kg/d on Days 1 to 7 by continuous IV infusion plus docetaxel 75 mg/m2 on Day 5 of each 21-day cycle for up to 8 cycles. Patients were assessed for response prior to Cycles 3, 5, and 7, at completion of treatment, and up to 18 months after randomization. Endpoints include time to progression, survival at 6 and 12 months post randomization, response rate (complete and partial), response duration, and safety.

Results: Of 298 patients randomized, 287 initiated treatment. Among all patients randomized, the median age was 63 years, and 61% of patients were male. A total of 86% of patients had Stage IV disease; 94% had metastatic disease; and 91% had an ECOG performance status of 0 or 1. Prior radiotherapy was reported for 39% of patients and prior paclitaxel therapy for 48%. Grade 4 neutropenia of 23% among all treated patients compared favorably with that historically reported with docetaxel alone.

Conclusions: The database will be unblinded in Quarter 2, 2007, and results presented.

Comments

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

Publication (Name of Journal)

Journal of Thoracic Oncology

DOI

https://doi.org/10.1097/01.JTO.0000283144.91294.05

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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