title: Phase I/II study of nab-paclitaxel plus gemcitabine for chemotherapy-naive Japanese patients with metastatic pancreatic cancer.
abstract: OBJECTIVE
  Efficacy and safety of nab-paclitaxel plus gemcitabine have not been clarified in Japanese patients with metastatic pancreatic cancer. No pharmacokinetic profile of co-administration of nab-paclitaxel and gemcitabine has been reported. We conducted a phase I/II study of the efficacy, safety, and pharmacokinetics in Japanese patients with metastatic pancreatic cancer.
  
  
  METHODS
  The patients were administered 125 mg/m(2) nab-paclitaxel followed by 1000 mg/m(2) gemcitabine on day 1, 8, and 15 every 4 weeks. Treatment was continued until disease progression, unacceptable adverse events, or withdrawal of consent, whichever occurred first. The primary endpoints were tolerability in phase I and overall response rate according to RECIST in phase II.
  
  
  RESULTS
  A total of 34 patients were enrolled. At the time of 1-year follow-up analysis since the last patient enrollment, the objective response rate by independent review committee was 58.8% (20 of 34 patients; 95% confidence interval [CI], 40.7-75.4%). The median progression-free survival and median overall survival were 6.5 months (95% CI, 5.1-8.3) and 13.5 months (95% CI, 10.6--not reached), respectively. Main adverse drug reactions of grade 3 or higher were neutropenia (70.6%), leukopenia (55.9%), anemia (14.7%), lymphocytopenia (14.7%), thrombocytopenia (14.7%), and peripheral sensory neuropathy (11.8%). There were no treatment-related deaths and no marked differences in pharmacokinetics of combined paclitaxel and gemcitabine in historical comparison between co-administration and monotherapies.
  
  
  CONCLUSIONS
  Nab-paclitaxel plus gemcitabine regimen showed highly promising efficacy with manageable safety profile under careful observation and with appropriate supportive care in Japanese patients with metastatic pancreatic cancer.
  
  
  BACKGROUND
  JapicCTI-121987.
authors: Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. hiueno@ncc.go.jp.
authors: Hideki
authors: H
authors: Ueno
authors: Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
authors: Masafumi
authors: M
authors: Ikeda
authors: Division of Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center, Yokohama, Japan.
authors: Makoto
authors: M
authors: Ueno
authors: Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan.
authors: Nobumasa
authors: N
authors: Mizuno
authors: Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors: Tatsuya
authors: T
authors: Ioka
authors: Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
authors: Yasushi
authors: Y
authors: Omuro
authors: Department of Medical Oncology, St.Marianna University School of Medicine Hospital, Kawasaki, Japan.
authors: Takako Eguchi
authors: TE
authors: Nakajima
authors: Department of Medical Oncology, Kyorin University School of Medicine, Tokyo, Japan.
authors: Junji
authors: J
authors: Furuse
mesh_terms: D000328:Adult; D000368:Aged; D000418:Albumins / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D044466:Asian People; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D003841:Deoxycytidine; D017239:Paclitaxel; D000093542:Gemcitabine
keywords: Combination chemotherapy; Gemcitabine; Nab-paclitaxel; Pancreatic cancer; Pharmacokinetics