Related Experiment Video
Updated: Jul 30, 2026
Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer
Published on: February 12, 2017
A pilot trial of G3139, a bcl-2 antisense oligonucleotide, and paclitaxel in patients with chemorefractory small-cell
C M Rudin1, G A Otterson, A M Mauer
1Section of Hematology/Oncology, University of Chicago Medical Center, IL 60637-1470, USA. crudin@medicine.bsd.uchicago.edu
Background:
Chemorefractory small-cell lung cancer (SCLC) is defined as disease that progresses during primary therapy or within 3 months of completion of primary therapy. Patients with chemorefractory SCLC have a very poor prognosis, and no treatment has been shown to be of significant clinical benefit. Elevated expression of Bcl-2 is found in the majority of SCLCs and has been associated with therapeutic resistance. Suppression of Bcl-2 levels through the use of G3139, an antisense oligonucleotide complementary to the mRNA encoding Bcl-2, might increase the antitumor efficacy of cytotoxic therapy.
Patients And Methods:
Twelve patients with chemorefractory SCLC participated in this pilot trial of paclitaxel combined with G3139. G3139 was given by continuous i.v. infusion over 7 days at a fixed dose of 3 mg/kg/day. Paclitaxel dose was initially 175 mg/m2 on day 6, but was decreased to 150 mg/m2 due to myelosuppression observed in two of the three patients treated in the first dose cohort.
Results:
The combination of paclitaxel at 150 mg/m2 and G3139 at 3 mg/kg/day was found to be feasible and well tolerated. No objective responses were observed, but two patients had stable disease, one remaining stable on therapy for >30 weeks. Plasma G3139 levels were determined, and were found to be highest in the patient with prolonged stable disease, suggesting that individual variation in metabolism and clearance of the antisense oligonucleotide may influence activity.
Conclusions:
This study demonstrates that G3139 can be combined with paclitaxel in a cytotoxic dose range, and suggests that a similar combination be tested for activity in the context of chemoresponsive disease.
Insights
This pilot study combined paclitaxel with G3139 to treat refractory small-cell lung cancer (SCLC). The combination was feasible, but did not show objective responses, suggesting further investigation in chemoresponsive SCLC.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Chemorefractory small-cell lung cancer (SCLC) has a poor prognosis with limited treatment options.
- Elevated Bcl-2 expression in SCLC is linked to therapeutic resistance.
- G3139, an antisense oligonucleotide, targets Bcl-2 mRNA to potentially enhance chemotherapy efficacy.
Purpose of the Study:
- To evaluate the feasibility and tolerability of combining paclitaxel with G3139 in patients with chemorefractory SCLC.
- To explore the preliminary activity of this combination therapy.
Main Methods:
- A pilot trial involving twelve patients with chemorefractory SCLC.
- G3139 administered via continuous i.v. infusion (3 mg/kg/day) over 7 days.
- Paclitaxel administered at 150 mg/m2 on day 6, following dose reduction from 175 mg/m2 due to myelosuppression.
Main Results:
- The combination of paclitaxel (150 mg/m2) and G3139 (3 mg/kg/day) was feasible and well-tolerated.
- No objective responses were observed; however, two patients achieved stable disease.
- One patient with stable disease for over 30 weeks had the highest plasma G3139 levels, suggesting potential influence of individual pharmacokinetics.
Conclusions:
- G3139 can be safely combined with paclitaxel in a cytotoxic dose range for SCLC.
- Further investigation of this combination is warranted, particularly in chemoresponsive SCLC settings.
