title: A phase II study of biweekly S-1 and paclitaxel (SPA) as first-line chemotherapy in patients with metastatic or advanced gastric cancer.
abstract: OBJECTIVE
  Paclitaxel and S-1 are both effective antitumor chemotherapeutic agents for advanced gastric cancer. However, the continuous administration of S-1 for 3 weeks or more can result in unacceptable toxicities, particularly hematological toxicities. Therefore, an alternative treatment schedule (1-week administration followed by 1-week rest) is warrant for testing in order to allow continuation of the therapy. We evaluate the efficacy and safety of biweekly S-1 and paclitaxel (SPA) as first-line chemotherapy in patients with metastatic or advanced gastric cancer.
  
  
  METHODS
  Patients with previously untreated advanced or relapsed gastric cancer who had measurable lesion(s) were enrolled. Paclitaxel was administered intravenously at a dose of 120 mg/m(2) on day 1 and oral S-1 was given twice daily (BSA < 1.25 m(2), 80 mg/day; 1.25 ≤ BSA < 1.50 m(2), 100 mg/day; 1.50 m(2) ≤ BSA, 120 mg/day) on days 1-7 followed by a drug-free interval of 1 week every 14-day cycle.
  
  
  RESULTS
  Forty-four patients (M/F = 33/11) were enrolled. A total of 277 chemotherapy cycles were administered, with a median of six cycles per patient (range 1-12), and 19 (43.2 %) patients received up to seven cycles. The assessed overall response rate was 38.6 with 38.6 % partial response in 17 patients, 45.4 % stable disease in 20 patients, and 13.6 % progressive disease in six patients. Thirty-four patients (77.3 %) received second-line chemotherapy. The estimated median progression-free survival and median overall survival times were, respectively, 5.2 months (95 % CI 4.08-6.39 months) and 12.2 months (95 % CI 8.81-15.60 months). The major hematological toxicities were included grade 3 leucocytopenia in two patients (4.5 %), grade 3 neutropenia in 14 patients (40.9 %), and grade 4 neutropenia in four patients (9.0 %). Two patients (4.5 %) suffered grade 1 febrile neutropenia. All grade of the non-hematological toxicities, such as nausea, vomiting, alopecia, and diarrhea, held the proportion of 54.5 % (grade 3/4, 4.5 %), 31.8, 95.4, and 18.1 % (grade 3/4, 2.2 %), respectively.
  
  
  CONCLUSIONS
  Biweekly S-1 and paclitaxel (SPA regimen) combination therapy had promising activity with acceptable adverse toxicities. SPA regimen was easily implemented, and more patients received second-line chemotherapy. It deserved to conduct a well-designed randomized phase III study to compare this regimen with S-1-based combination treatment.
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Rd., Hangzhou, 310003, Zhejiang, People's Republic of China.
authors.forename: Haiping
authors.initials: H
authors.lastname: Jiang
authors.forename: Jiong
authors.initials: J
authors.lastname: Qian
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.forename: Chenyu
authors.initials: C
authors.lastname: Mao
authors.forename: Yulong
authors.initials: Y
authors.lastname: Zheng
authors.forename: Linghong
authors.initials: L
authors.lastname: Chen
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.forename: Haibo
authors.initials: H
authors.lastname: Mou
authors.forename: Weijia
authors.initials: W
authors.lastname: Fang
authors.forename: Lisong
authors.initials: L
authors.lastname: Teng
authors.forename: Nong
authors.initials: N
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
chemical_list: D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D017239:Paclitaxel