title: Multicenter phase 2 study of interleukin-2 and 13-cis retinoic acid as maintenance therapy in advanced non-small-cell lung cancer.
abstract: High serum levels of vascular endothelial growth factor (VEGF) are a poor prognostic factor for patients with advanced non-small-cell lung cancer (NSCLC). We have previously shown that low-dose interleukin (IL)-2 and 13-cis retinoic acid (RA) decreased VEGF and improved the immune function of patients with advanced tumors treated with chemotherapy. The primary end point of this study was to verify whether IL-2 and RA decreased serum VEGF in NSCLC patients showing a clinical benefit from chemotherapy. The secondary end point was the evaluation of clinical outcome. We treated 38 patients with advanced NSCLC who had a complete or partial response or disease stability to chemotherapy and had a median serum VEGF level of 508 ng/mL; as maintenance therapy, they received subcutaneous IL-2 (1.8 x 10(6) IU) and oral RA. Matched controls (n = 87) were selected from a large cohort of patients with a similar disease status, including clinical benefit from chemotherapy. The most common adverse events were mild cutaneous skin rash and fever. Serum VEGF decreased to a mean level of 152 ng/mL (P = 0.0002). A statistically significant improvement in immune function was observed (lymphocyte and natural killer cell numbers and CD4+/CD8+ ratio) with respect to baseline values and controls. An improvement in the clinical outcome was also observed compared with controls. These data show that the administration of low-dose subcutaneous IL-2 and oral RA to patients with advanced NSCLC showing a clinical benefit from chemotherapy is feasible with a low-toxicity profile, decreases VEGF, and seems to improve progression-free and overall survival.
authors.affiliation: Unità Operativa di Oncologia, Ospedale Civile di Avezzano, Avezzano, Italy. frecchia1946@libero.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Recchia
authors.forename: Gaetano
authors.initials: G
authors.lastname: Saggio
authors.forename: Antonio
authors.initials: A
authors.lastname: Nuzzo
authors.forename: Edoardo
authors.initials: E
authors.lastname: Biondi
authors.forename: Anna
authors.initials: A
authors.lastname: Di Blasio
authors.forename: Alisia
authors.initials: A
authors.lastname: Cesta
authors.forename: Giampiero
authors.initials: G
authors.lastname: Candeloro
authors.forename: Edoardo
authors.initials: E
authors.lastname: Alesse
authors.forename: Silvio
authors.initials: S
authors.lastname: Rea
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D015474:Isotretinoin / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D007376:Interleukin-2; D042461:Vascular Endothelial Growth Factor A; D015474:Isotretinoin