Regimen May Hike Survival in Advanced Cancer

Patients with advanced and metastatic cancers had "unexpected 5-year survival" when treated with an inexpensive maintenance immunotherapy that boosted levels of natural killer cells, investigators reported here.

Patients with a variety of stage IV cancers had substantially better overall survival when they received the combination of interleukin-2 and 13-cis retinoic acid after chemotherapy that produced stable disease or better response.

As compared with historical survival data, the regimen was associated with a twofold or greater improvement in 5-year survival.

The maintenance therapy was well tolerated, including no grade 3-4 toxicity, Francesco Recchia, MD, reported at the American Association for Cancer Research meeting.

"The administration of IL-2 and retinoic acid results - with a modest toxicity profile - in a sustained improvement in natural killer (NK) cells, a decrease in vascular endothelial growth factor (VEGF), and unexpected 5-year survival rates," Recchia, of Ospedale Civile di Avezzano in Avezzano, Italy, said during a press briefing at the AACR meeting.

More than a decade ago, Recchia and colleagues found that the maintenance regimen improved immunologic parameters associated with more favorable prognosis in advanced cancer (Clin Cancer Res 2001; 7: 1251-1257). At least two patients who had partial responses to chemotherapy subsequently had complete responses during maintenance therapy.

The investigators took an interest in the immunotherapeutic doublet because of what they perceived as an unmet need for an inexpensive, minimally-toxic maintenance therapy to prolong responses achieved with conventional chemotherapy. The 18-patient initial clinical experience has since grown into a 500-patient study involving patients with advanced-stage solid tumors.

The IL-2/13-cis retinoic acid combination had clinical appeal for several reasons: IL-2 has no known cross-resistance with chemotherapy and improves disease-associated lymphocytopenias, which are associated with poor prognosis. The retinoid has immunodulatory properties and potential synergy with IL-2.

Patients eligible for the maintenance regimen had achieved stable disease or objective response (complete or partial) to chemotherapy. They self-administered the drugs (subcutaneously for IL-2, orally for 13-cis-retinoic acid) five days a week for two 3-week courses, followed by a week off therapy. Treatment continued for a year, followed by intermittent therapy for five years or until disease progression.

The primary objective was to determine whether the maintenance therapy increased levels of NK cells and reduced levels of VEGF. Secondary endpoints were disease-free survival (DFS), overall survival, and toxicity.

Investigators assessed NK levels, VEGF levels, tumor response, and toxicity every four months.