title: Phase I trial of capecitabine plus everolimus (RAD001) in patients with previously treated metastatic gastric cancer.
abstract: OBJECTIVE
  Everolimus is a novel inhibitor of the mammalian target of rapamycin pathway, which is aberrantly activated in cancer cell. We conducted a phase I study of capecitabine plus everolimus (RAD001) in refractory gastric cancer patients.
  
  
  METHODS
  Patients with metastatic gastric cancer and progression after prior chemotherapy were eligible. Four dose levels were planned as follows: Level 1, 5 mg bid/day of everolimus (D1-D21) and 500 mg/m(2) bid/day of capecitabine (D1-14); Level 2, 5 mg bid/day of everolimus (D1-D21) and 750 mg/m(2) bid/day of capecitabine (D1-14); Level 3, 5 mg bid/day of everolimus (D1-D21) and 1000 mg/m(2) bid/day of capecitabine (D1-14); and Level 4, 10 mg bid/day of everolimus (D1-D21) and 1000 mg/m(2) bid/day of capecitabine (D1-14). Treatment was repeated every 3 weeks until disease progression, patient refusal, or any serious adverse event.
  
  
  RESULTS
  Fifteen patients were enrolled in this study between November 2009 and April 2010. Fifteen patients were enrolled (median age, 50 years; men, 9). Six patients had received two previous chemotherapy regimens; six patients had three previous chemotherapy regimens before the study treatment. Thus, the majority of patients were heavily pretreated. The dose-limiting toxicities were grade 3 infection, grade 3 mucositis, and grade 3 hyperglycemia and hyponatremia. After a median follow-up duration of 5.6 months (range, 2.3-8.1 months), median PFS was 1.8 months (95% CI, 0.8-2.8 months). The maximum best change observed was a 28.7% decrease in sum of longest diameters when compared with baseline.
  
  
  CONCLUSIONS
  The combination of capecitabine and everolimus showed satisfactory toxicity profile and modest clinical benefit in patients with refractory gastric cancer. The recommended dose of capecitabine and everolimus was 650 mg/m(2) twice daily and 5 mg twice daily, respectively.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center Sungkyunkwan, University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, Korea.
authors.forename: Taekyu
authors.initials: T
authors.lastname: Lim
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Lee
authors.forename: Duk Joo
authors.initials: DJ
authors.lastname: Lee
authors.forename: Ha Yeon
authors.initials: HY
authors.lastname: Lee
authors.forename: Boram
authors.initials: B
authors.lastname: Han
authors.forename: Kyung Kee
authors.initials: KK
authors.lastname: Baek
authors.forename: Hee Kyung
authors.initials: HK
authors.lastname: Ahn
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Park
authors.forename: Joon Oh
authors.initials: JO
authors.lastname: Park
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Park
authors.forename: Ho Yeong
authors.initials: HY
authors.lastname: Lim
authors.forename: Kyoung-Mee
authors.initials: KM
authors.lastname: Kim
authors.forename: Won Ki
authors.initials: WK
authors.lastname: Kang
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D000068338:Everolimus; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D003841:Deoxycytidine; D000069287:Capecitabine; D000068338:Everolimus; D005472:Fluorouracil; D020123:Sirolimus