Targeted therapy and anti-angiogenesis are currently buzzwords in the field on oncology. Newer approaches to cancer treatment have focused on targeting specific receptors on cancer cell surface, and effecting cell kill by arresting new blood vessel development with anti-angiogenic agents. A number of agents in a variety of tumors have demonstrated activity by both of these routes, suggesting an interaction between the two pathways. In the US in 2003, 171,000 new cases of lung cancer are expected, resulting in 90,000 deaths from this disease. While chemotherapy for advanced non-small cell lung cancer (NSCLC) produces longer survival than supportive care, and two agent combinations appear superior to single agent intervention, the gains remain modest. Three large national randomized trials involving approximately 3000 patients randomized among various doublet treatments have yielded average response rates of 25%, median survivals averaging 8 months, and one-year survivals of 40%. No single two-drug regimen demonstrated superiority.

Invoking the Immune Response

The concept that an activated immune system might be beneficial to response and survival in NSCLC dates back to the 1970's observation that lung cancer patiens who had post-operative empyemas enjoyed longer survivals. Subsequent trials of non-specific immunostimulatory agents either failed to demonstrate benfit either alone or in combination with the chemotherapy, or were unduly toxic. Thus, immunologic approaches to lung cancer therapy remain investigational. CpG 7909 (ProMune), an investigational agent being tested in combination with chemotherapy for NSCLC, is an anti-sense strand of DNA complementary to a specific bacterial DNA, rich in a cytosine-guanine pattern that is responsible for immune reactivity to bacterial infections. It targets the TLR9 receptor, expressed only on dendritic cells and B-lymphocytes, so activity is specific with low incidence of undesirable side effets. Anti-tumor effect is mediated through antigen presentation, and enhanced production of cytokines such as interferon-inducible protein-10 (IP-10). which has anti-angiogenic activity.

Clinical Trial Eligibility

Our current trial, bing conducted in 15 sites nationally, allows investigator choice of one of four common regimens combining cisplatin or carboplatin with taxol or taxotere. Patients must have pathologically confirmed, untreated NSCLC, not surgically curable or metastatic (stages IIIB or IV) with measurable disease, a performance status of 70% and adequate hepatic, renal and hematologic function. Patients with autoimmune disease or other conditions requiring immunosuppressive agents, active infection or brain metastases are ineligible. Chemotherapy is given on a three weekly schedule, with CpG 7909 being administered subcutaneously on the non-chemotherapy weeks for up to 24 weeks in the absence of disease progression. Further information regarding this trial can be obtained through the Research Office at 760-416-4734.