In an extended phase II clinical trial of 500 patients with different types of stage 4 solid tumors who had responded to chemotherapy, a maintenance regimen with low-dose interleukin-2 and 13-cis retinoic acid has shown unexpected 5-year survival rates.

Low-dose interleukin-2 and retinoic acid give unexpected 5-year survival rates for patients with advanced cancers

In a clinical trial of 500 patients with different types of stage 4 solid tumors who had responded to chemotherapy, a maintenance regimen with low-dose interleukin-2 (IL-2) and 13-cis retinoic acid (RA) has shown unexpected 5-year survival rates.

Francesco Recchia, MD, director of oncology at the Civilian Hospital in Avezzano, Italy, is scheduled to present findings from this extended phase II study in a presentation at the American Association for Cancer Research Annual Meeting 2012 in Chicago on April 2.

The open, nonrandomized trial showed substantial improvements for these patients with metastatic cancer compared with corresponding U.S. National Cancer Institute Surveillance Epidemiology and End Results (SEER) data for 5-year overall survival (OS) rates. The OS rate was 42.7% for patients in the study versus 23.3% for breast cancer patients accounted for in SEER data, and 26.4% versus 3.6% for lung cancer patients, 43.6% versus 11.7% for colorectal cancer patients, and 23% versus 11% for renal cancer patients.

Recchia's research with low-dose IL-2 maintenance therapy dates back to 1995, when a patient with metastatic melanoma who did not tolerate high-dose IL-2 therapy was treated with lower doses and had a long-lasting response. Recchia and his colleagues followed up with a series of clinical trials of IL-2, including phase I and II randomized studies that, in some instances, added RA to the treatment regimen. The combination of the 2 agents succeeded in increasing natural killer (NK) cell populations and decreasing expression of VEGF—both associated with slowing cancer growth.

Initially, the patients self-injected IL-2 and took RA pills 5 days a week for 2 consecutive cycles of 3 weeks, with a 1-week rest period in between. Therapy then continued on an intermittent schedule, adjusted for patient immunocompetence, for 5 years or until disease progression. After 5 years, patients overall nearly doubled their mean NK cell populations and showed a dramatic reduction in their VEGF expression levels.

“The best merit of our research is the low cost of this therapy,” says Recchia, who adds that a phase III randomized trial for patients with advanced breast cancer is being led by Andrea Nicolini, MD, of the University of Pisa, Italy.