title: Raltitrexed/5-fluorouracil-based combination chemotherapy regimens in anticancer therapy.
abstract: Preclinical evidence of a schedule-dependent synergism between raltitrexed and 5-fluorouracil (5-FU) has prompted clinical studies of this combination. We review the main preclinical and clinical results of raltitrexed/5-FU-based combination chemotherapy regimens in anticancer therapy. Promising results include: response rates of 25 and 23% with combinations of raltitrexed/5-FU/levofolinic acid (LFA) as first-line treatment and oxaliplatin/raltitrexed/5-FU/LFA as second-line treatment of metastatic colorectal cancer, respectively; and a 67% response rate in a phase I study of cisplatin/raltitrexed/5-FU/LFA as first-line treatment of advanced head and neck cancer, including a 100% response rate at the recommended dose. These combinations were well tolerated, with neutropenia as the main dose-limiting toxicity, allowing the drugs to be combined at the doses used in monotherapy. These results suggest a role for raltitrexed within combination regimens in colorectal cancer therapy, as well as other tumors such as head and neck cancer. A further potential application of raltitrexed in combination therapies is within multidisciplinary chemo-radiotherapy strategies, mainly in rectal cancer. Phase II studies are planned/ongoing to investigate these interesting possibilities.
authors.affiliation: Southern Italy Cooperative Oncology Group, c/o National Tumor Institute of Naples, Via M Semmola, 80131 Napoli, Italy. fracap@sirio-oncology.it
authors.forename: F
authors.initials: F
authors.lastname: Caponigro
authors.forename: A
authors.initials: A
authors.lastname: Avallone
authors.forename: A
authors.initials: A
authors.lastname: Budillon
authors.forename: P
authors.initials: P
authors.lastname: Comella
authors.forename: G
authors.initials: G
authors.lastname: Comella
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000473:pathology; D005472:Fluorouracil / Q000008:administration & dosage*; D006258:Head and Neck Neoplasms / Q000188:drug therapy; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage*; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011799:Quinazolines / Q000008:administration & dosage*; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D013876:Thiophenes / Q000008:administration & dosage*
chemical_list: D009944:Organoplatinum Compounds; D011799:Quinazolines; D013876:Thiophenes; D000077150:Oxaliplatin; C068874:raltitrexed; D002955:Leucovorin; D005472:Fluorouracil