title: Cisplatin, cytarabine, caffeine, and continuously infused 5-fluorouracil (PACE) in the treatment of advanced pancreatic carcinoma: a phase II study.
abstract: Encouraging results using cisplatin, cytarabine, and caffeine for the treatment of pancreatic carcinoma prompted a phase II study using these agents and adding continuous intravenous infusion (CI) 5-fluorouracil (5-FU) (PACE). Patients with advanced pancreatic adenocarcinoma who had not received prior cytotoxic therapy were eligible. Treatment consisted of the following: on day 1, the administration of cisplatin 100 mg/m2 IV, cytarabine 2 g/m2 IV every 12 hours x 2 doses, and caffeine 400 mg/m2 subcutaneously after each cytarabine dose; and on days 3 to 21, 5-FU 250 mg/m2/day given by CI. Cycles were repeated every 28 days. Thirty eligible patients were entered in the study. The median number of cycles received was three. Grade IV neutropenia and thrombocytopenia occurred in 53% and 27% of patients, respectively. Among 30 treated patients, complete remission (CR) was seen in 2 patients and partial remission (PR) in 3 patients, for an overall response rate of 16.7% (95% confidence interval 6.8-32.4%). The median survival was 5.0 months (range: 0.3-32.4 months) and 16.7% and 10% of patients were alive at 1 and 2 years. respectively. Changes in the serum level of CA 19-9 provided an early marker of response which translated in differences in survival. Those with increasing or decreasing/stable levels of CA 19-9 after the first cycle of therapy had median survivals of 1.7 and 8.3 months, respectively (p = 0.0002). Although PACE chemotherapy produced durable responses in pancreatic cancer, the toxicity was substantial. A modification of this regimen with newer, less toxic drugs may provide better results and reduced toxicity. Also, the monitoring of the serum CA 19-9 level may provide a means to assess response and predict survival.
authors.affiliation: Department of Medicine, Barbara Ann Karmanos Cancer Institute, Wayne State University and Detroit Medical Center, Michigan, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ahmed
authors.forename: V K
authors.initials: VK
authors.lastname: Vaitkevicius
authors.forename: M M
authors.initials: MM
authors.lastname: Zalupski
authors.forename: W
authors.initials: W
authors.lastname: Du
authors.forename: P
authors.initials: P
authors.lastname: Arlauskas
authors.forename: C
authors.initials: C
authors.lastname: Gordon
authors.forename: C
authors.initials: C
authors.lastname: Kellogg
authors.forename: A F
authors.initials: AF
authors.lastname: Shields
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D018395:CA-19-9 Antigen / Q000097:blood; D002110:Caffeine / Q000008:administration & dosage* / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D016001:Confidence Intervals; D003561:Cytarabine / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D012074:Remission Induction; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D010726:Phosphodiesterase Inhibitors; D003561:Cytarabine; D002110:Caffeine; D002945:Cisplatin; D005472:Fluorouracil