Elsevier

Journal of Thoracic Oncology

Volume 3, Issue 9, September 2008, Pages 1018-1025
Journal of Thoracic Oncology

Original Article
Phase I/II Study of Vinorelbine and Exisulind as First-Line Treatment of Advanced Non-small Cell Lung Cancer in Patients at Least 70 Years Old: A Wisconsin Oncology Network Study

https://doi.org/10.1097/JTO.0b013e3181834fa1Get rights and content
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Introduction

Exisulind is an apoptotic agent with preclinical activity in non-small cell lung cancer (NSCLC). Vinorelbine is safe and effective in older patients with advanced NSCLC. We assessed these agents together as palliative treatment for older patients with advanced NSCLC.

Methods

Chemotherapy-naive patients ≥70-years-old with stage IIIB-IV NSCLC and a performance status (PS) ≤2 were eligible. Primary endpoints were the maximum tolerated dose (phase I) and time-to-progression (phase II) of oral exisulind with 25 mg/m2/wk of intravenous vinorelbine on a 28-day cycle. Patients with clinical benefit after 6 cycles of this combination received exisulind alone.

Results

Fourteen phase I patients (median PS 1; median age 78 years) were enrolled. Dose-limiting toxicities included grade 3 constipation (one patient), grade 3 febrile neutropenia (one patient) and grade 3 diarrhea (one patient). The maximum tolerated dose of oral exisulind with 25 mg/m2/wk of intravenous vinorelbine was 125 mg twice daily. Thirty phase II patients (median PS 1; median age 78 years) were enrolled. Grade ≥3 neutropenia occurred in 14/30 patients. Two patients experienced neutropenic fever. There were no complete responses, one partial response and 12 patients with stable disease as their best response. The objective response rate was 4.0% (95% CI: 0.1-20.4%). Phase II median time-to-progression was 4.7 months (95% CI: 3.1-9.3 months) and median OS was 9.6 months (95% CI: 6.6-19.1 months).

Conclusions

This combination is safe, seems to have activity in the elderly with advanced NSCLC and a PS ≤2, and warrants further investigation.

Key Words

Elderly
Exisulind
Sulindac sulfone
Non-small cell lung cancer
Vinorelbine
Phase I
Phase II

Cited by (0)

Supported by P30 CA14520 (KMK) and National Institutes of Health grant T32 CA009614 Physician Scientist Training in Cancer Medicine (SA), and OSI Pharmaceuticals (Melville, NY).

Disclosure: KMK serves as consultant to OSI on an unrelated project, not involving exisulind.