title: Phase II clinical trial of S-1 plus oral leucovorin in previously treated patients with non-small-cell lung cancer.
abstract: BACKGROUND
  S-1, a novel oral fluoropyrimidine, has potent antitumor activity against non-small-cell lung cancer (NSCLC). Meanwhile, leucovorin enhances the efficacy of 5-fluorouracil by inhibiting thymidylate synthase. Therefore, this phase II clinical trial evaluated the safety and efficacy of S-1 plus leucovorin combination therapy for previously treated patients with NSCLC.
  
  
  METHODS
  Patients with stage IIIB or IV NSCLC were prospectively enrolled if they received 1 or 2 prior chemotherapy regimens. S-1 (40-60 mg) and leucovorin (25mg) were administered together orally twice per day for 7 consecutive days followed by 7 days of rest. This 2-week cycle was repeated for a maximum of 25 cycles until the onset of disease progression or unacceptable adverse events. Endpoints included objective tumor response, progression-free survival, overall survival, and safety.
  
  
  RESULTS
  Among 33 patients, 6 (18.2%), 14 (42.4%), and 11 (33.3%) had partial response, stable disease, and progressive disease, respectively. Median progression-free and overall survival times were 3.5 and 11.7 months, respectively. The common grade 3 toxicities included stomatitis (18.2%), anorexia (12.1%), and neutropenia (9.1%). One patient had pneumatosis cystoides intestinalis, and another experienced paralytic ileus. There were no treatment-related deaths.
  
  
  CONCLUSIONS
  S-1 plus leucovorin combination therapy demonstrated promising efficacy and an acceptable toxicity profile in previously treated patients with NSCLC.
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Japan. Electronic address: t.naito@scchr.jp.
authors.forename: T
authors.initials: T
authors.lastname: Naito
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Seto
authors.affiliation: Department of Clinical Oncology, Osaka City General Hospital, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Division of Thoracic Oncology, National Cancer Center Hospital East, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Goto
authors.affiliation: Center for Clinical and Translational Research, Kyushu University Hospital, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Okamoto
authors.affiliation: Department of Medical Oncology, Kinki University School of Medicine, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ohba
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Murakami
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Biostatistics, Yokohama City University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yamanaka
authors.affiliation: Third Department of Internal Medicine, Wakayama Medical University, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004338:Drug Combinations; D064420:Drug-Related Side Effects and Adverse Reactions / Q000145:classification / Q000473:pathology*; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D005641:Tegafur / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D002955:Leucovorin
keywords: Chemotherapy; Fluoropyrimidine; Leucovorin; Non-small-cell lung cancer; Phase II clinical trial; S-1