Immunotherapy in patients with less than complete response to chemotherapy

Patients with metastatic solid tumors (MST) with less than a complete response to chemotherapy (L-CR), a depressed immune system and elevated serum vascular endothelial growth factor (VEGF) lack defined treatment options. The primary endpoint evaluated in this study was whether interleukin-2 (IL-2) and 13-cisretinoic acid (RA) treatment reduced VEGF and improved immune function in such patients. Secondary endpoints were objective response, relapse-free survival (RFS), and overall survival (OS).

One hundred consecutive MST patients with L-CR and a mean serum VEGF of 421.0 pg/mm3 were enrolled. Patients self-administered subcutaneous IL-2 1.8 x 10(6) IU/day, and oral RA 0.5 mg/kg/day x 5 days/week for 2 cycles of 3 weeks/month for 1 year and continued until progression.

After a median follow-up of 78 months, a statistically significant VEGF decrease and improvements in lymphocyte, NK, and CD4+/CD8+ ratio were observed. Twenty-four patients were converted to a CR; their 5-year RFS and OS rates were each 96%. No WHO grade 3 or 4 toxicities were observed.

Administration of IL-2/RA to this patient population produced a significant decrease in VEGF, improvement of prognostically relevant immunological parameters, and durable response in 25% of patients.