Article Text

Download PDFPDF

PF-3512676 may enhance the clinical activity of taxane/platinum chemotherapy in advanced non-small cell lung cancer
  1. A Osman
  1. Dr A Osman, Respiratory Medicine, University Hospital of North Staffordshire, Stoke-on-Trent, Staffordshire, UK; ayman.osman{at}

Statistics from

Current first-line therapy for stage IIIB–IV non-small-cell lung cancer (NSCLC) is taxane plus platinum-based chemotherapy. With this regime the 1-year survival rate is less than 40%. Toll-like receptors (TLR) can stimulate innate and antigen-specific acquired immunity. PF-3512676 is a TLR9-activating oligodeoxynucleotide and has confirmed antitumour activity against a variety of cancers.

This randomised phase II study examined the safety and antitumour action of the combination of PF-3512676 and taxane/platinum chemotherapy in stage IIIB–IV NSCLC. One hundred and twelve patients were included from 26 centres. All patients had adequate blood counts, renal and hepatic function and had received no previous chemotherapy. Patients with autoimmune diseases or brain metastasis were excluded. Seventy-three patients received chemotherapy plus PF-3512676 and 37 patients received chemotherapy alone.

The observed response rate (assessed as a complete or partial response based on investigator assessment) was higher in the PF-3512676 group than in the group receiving chemotherapy alone (38% vs 19%). Although not all responses were confirmed radiologically, the authors felt that the response rate would have been even higher in the PF-3512676 arm if this had been the case. Despite more patients with stage IV disease in the PF-3512676 group, the median survival was 12.3 months compared with 6.8 months in the group receiving chemotherapy alone, with 1-year survival rates of 50% and 33%, respectively.

The addition of PF-3512676 was generally well tolerated. Phase III trials are in progress and may provide further evidence that the addition of PF-3512676 to taxane/platinum chemotherapy is safe and may prolong survival.

▸ Manegold C, Gravenor D, Woytowitz D, et al. Randomized phase II trial of a Toll-like receptor 9 agonist oligodeoxynucleotide, PF-3512676, in combination with first-line taxane plus platinum chemotherapy for advanced-stage NSCLC. J Clin Oncol 2008;26:3979–86.

View Abstract

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.