Pilot phase IIA study for evaluation of the efficacy of folic acid in the treatment of laryngeal leucoplakia

Abstract

BACKGROUNDIt has been previously observed that patients with head and neck squamous cell carcinoma or with laryngeal leucoplakia present a significant reduction in plasma folate levels. The current Phase IIA pilot study assessed the effectiveness of folic acid as a chemopreventive agent in patients affected by glottic laryngeal leucoplakia,METHODSForty‐three untreated patients affected by glottic laryngeal leucoplakia were enrolled in the Ear, Nose, and Throat Department (Universita Cattolica del Saco Cuore, Rome, Italy). Glottic leucoplakia was initially diagnosed by indirect laryngoscopy and successively confirmed by diagnostic direct microlaryngoscopy with a biopsy for histologic assessment. Folic acid (Folina, Schwarz Pharma, Germany) was administered orally (5 mg every 8 hours) for 6 months. Patients were monitored every 30 days by videolaryngoscopy.RESULTSTwelve (28%) patients had no response, 19 (44%) had a partial response, and 12 (28%) had a complete response. The mean increase in serum folate levels (10.06 ± 0.53) and the mean decrease in homocysteine serum (3.65349 ± 0.85526) at the end of the study were highly significant (P = .0001).CONCLUSIONSThe larynx is 1 of the sites of major interest and a good model for the development of chemopreventive agents, but so far the proposed agents have shown no clear efficacy on precancerous lesions or on the development of second malignancies. Cancer 2006. © 2006 American Cancer Society.

High-Frequency, Magnetic-Field-Responsive Drug Release from Magnetic Nanoparticle/Organic Hybrid Based on Hyperthermic Effect

“…To accomplish more effective accumulation, the application of biological recognition mechanism is useful. For example, the α-COOH of folic acid (FA) specifically binds to folate receptors (FRs) overexpressed in breast cancer tumors − , and therefore, FA-modified MNPs without the loss of α-COOH can selectively target tumors. We have succeeded in chemoselective modification of MNPs with FA through the application of alkyne−azide click chemistry.…”

Chemoselective Synthesis of Folic Acid−Functionalized Magnetite Nanoparticles via Click Chemistry for Magnetic Hyperthermia

“…(1) easy availability; (2) low cost; (3) applicability over a wide range of tumors, such as laryngeal, ovarian, endometrial, colorectal, breast, lung, renal-cell, and neuroendocrine carcinomas; [10][11][12][13][14] (4) ease of cytosolic delivery when combined with magnetic NPs, because the FR-targeting ligand complex can be internalized via endocytosis; and (5) potential for repeated administration, because of its small size, as compared to other targeting ligands. The R-carboxyl group and not the γ-carboxyl group of FA (see Scheme 2, presented later in this paper) is essential for high-affinity binding to FRs on human tumors.…”

“…This is because FA has a high affinity for folate receptors (FRs), which are overexpressed in various types of human tumors but generally are absent in most normal tissues . FA has several advantages over macromolecules (such as monoclonal antibodies) as a tumor-targeting ligand: (1) easy availability; (2) low cost; (3) applicability over a wide range of tumors, such as laryngeal, ovarian, endometrial, colorectal, breast, lung, renal-cell, and neuroendocrine carcinomas; − (4) ease of cytosolic delivery when combined with magnetic NPs, because the FR-targeting ligand complex can be internalized via endocytosis; and (5) potential for repeated administration, because of its small size, as compared to other targeting ligands. The α-carboxyl group and not the γ-carboxyl group of FA (see Scheme , presented later in this paper) is essential for high-affinity binding to FRs on human tumors. , Therefore, the α-carboxyl group should not be modified or substituted when FA is immobilized on magnetic NPs for the delivery and accumulation in tumors.…”