PANCREOX: A Randomized Phase III Study of Fluorouracil/Leucovorin With or Without Oxaliplatin for Second-Line Advanced Pancreatic Cancer in Patients Who Have Received Gemcitabine-Based Chemotherapy.
Purpose The standard of care for second-line therapy in patients with advanced pancreatic cancer after gemcitabine-based therapy is not clearly defined. The CONKO-003 phase III study reported a survival benefit with second-line fluorouracil (FU) and oxaliplatin using the oxaliplatin, folinic acid, and FU (OFF) regimen.1PANCREOX was a phase III multicenter trial to evaluate the benefit of FU and oxaliplatin administered as modified FOLFOX6 (mFOLFOX6; infusional fluorouracil, leucovorin, and oxaliplatin) versus infusional FU/leucovorin (LV) in this setting. Patients and Methods Patients with confirmed advanced pancreatic cancer who were previously treated with gemcitabine therapy and with an Eastern Cooperative Oncology Group performance status of 0-2 were eligible. A total of 108 patients were randomly assigned to receive biweekly mFOLFOX6 or infusional FU/LV until progression. Progression-free survival (PFS) was the primary end point. Results Baseline patient characteristics were similar in both arms. No difference was observed in PFS (median, 3.1 months v 2.9 months; P = .99). Overall survival (OS) was inferior in patients assigned to mFOLFOX6 (median, 6.1 months v 9.9 months; P = .02). Increased toxicity was observed with the addition of oxaliplatin, with grade 3/4 adverse events occurring in 63% of patients who received mFOLFOX6 and 11% of those who received FU/LV. More patients in the mFOLFOX6 arm withdrew from study due to adverse events than in the FU/LV arm (20% v 2%), whereas the use of postprogression therapy was significantly higher in the FU/LV arm (25% v 7%; P = .015). No significant differences were observed in time to deterioration on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 global health scale. Conclusion No benefit was observed with the addition of oxaliplatin, administered as mFOLFOX6, versus infusional FU/LV in patients with advanced pancreatic cancer previously treated with first-line gemcitabine.
Sharlene Gill and Malcolm Moore, BC Cancer Agency, Vancouver; Muhammad Zulfiqar, BC Cancer Agency, Abbotsford; Thuan Do, BC Cancer Agency, Surrey; Wendy Yin Han Lam, Burnaby Hospital Cancer Centre, Burnaby, British Columbia; Yoo-Joung Ko, Sunnybrook Health Sciences Centre; Malcolm Moore, Princess Margaret Hospital, Toronto; Christine Cripps, Ottawa Hospital Cancer Centre, Ottawa; Sukhbinder Dhesy-Thind, Juravinski Cancer Centre, Hamilton; Pawel Zalewski, RSM Durham Regional Cancer Centre, Oshawa; Pablo Cano, Sudbury Regional Hospital, Sudbury, Ontario; Annie Beaudoin, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke; Helene Grassin and John Stewart, Sanofi Canada, Laval, Quebec; and Scot Dowden, Alberta Health Service, Calgary, Alberta, Canada.
Sharlene
S
Gill
Sharlene Gill and Malcolm Moore, BC Cancer Agency, Vancouver; Muhammad Zulfiqar, BC Cancer Agency, Abbotsford; Thuan Do, BC Cancer Agency, Surrey; Wendy Yin Han Lam, Burnaby Hospital Cancer Centre, Burnaby, British Columbia; Yoo-Joung Ko, Sunnybrook Health Sciences Centre; Malcolm Moore, Princess Margaret Hospital, Toronto; Christine Cripps, Ottawa Hospital Cancer Centre, Ottawa; Sukhbinder Dhesy-Thind, Juravinski Cancer Centre, Hamilton; Pawel Zalewski, RSM Durham Regional Cancer Centre, Oshawa; Pablo Cano, Sudbury Regional Hospital, Sudbury, Ontario; Annie Beaudoin, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke; Helene Grassin and John Stewart, Sanofi Canada, Laval, Quebec; and Scot Dowden, Alberta Health Service, Calgary, Alberta, Canada.
Yoo-Joung
YJ
Ko
Sharlene Gill and Malcolm Moore, BC Cancer Agency, Vancouver; Muhammad Zulfiqar, BC Cancer Agency, Abbotsford; Thuan Do, BC Cancer Agency, Surrey; Wendy Yin Han Lam, Burnaby Hospital Cancer Centre, Burnaby, British Columbia; Yoo-Joung Ko, Sunnybrook Health Sciences Centre; Malcolm Moore, Princess Margaret Hospital, Toronto; Christine Cripps, Ottawa Hospital Cancer Centre, Ottawa; Sukhbinder Dhesy-Thind, Juravinski Cancer Centre, Hamilton; Pawel Zalewski, RSM Durham Regional Cancer Centre, Oshawa; Pablo Cano, Sudbury Regional Hospital, Sudbury, Ontario; Annie Beaudoin, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke; Helene Grassin and John Stewart, Sanofi Canada, Laval, Quebec; and Scot Dowden, Alberta Health Service, Calgary, Alberta, Canada.
Christine
C
Cripps
Sharlene Gill and Malcolm Moore, BC Cancer Agency, Vancouver; Muhammad Zulfiqar, BC Cancer Agency, Abbotsford; Thuan Do, BC Cancer Agency, Surrey; Wendy Yin Han Lam, Burnaby Hospital Cancer Centre, Burnaby, British Columbia; Yoo-Joung Ko, Sunnybrook Health Sciences Centre; Malcolm Moore, Princess Margaret Hospital, Toronto; Christine Cripps, Ottawa Hospital Cancer Centre, Ottawa; Sukhbinder Dhesy-Thind, Juravinski Cancer Centre, Hamilton; Pawel Zalewski, RSM Durham Regional Cancer Centre, Oshawa; Pablo Cano, Sudbury Regional Hospital, Sudbury, Ontario; Annie Beaudoin, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke; Helene Grassin and John Stewart, Sanofi Canada, Laval, Quebec; and Scot Dowden, Alberta Health Service, Calgary, Alberta, Canada.
Annie
A
Beaudoin
Sharlene Gill and Malcolm Moore, BC Cancer Agency, Vancouver; Muhammad Zulfiqar, BC Cancer Agency, Abbotsford; Thuan Do, BC Cancer Agency, Surrey; Wendy Yin Han Lam, Burnaby Hospital Cancer Centre, Burnaby, British Columbia; Yoo-Joung Ko, Sunnybrook Health Sciences Centre; Malcolm Moore, Princess Margaret Hospital, Toronto; Christine Cripps, Ottawa Hospital Cancer Centre, Ottawa; Sukhbinder Dhesy-Thind, Juravinski Cancer Centre, Hamilton; Pawel Zalewski, RSM Durham Regional Cancer Centre, Oshawa; Pablo Cano, Sudbury Regional Hospital, Sudbury, Ontario; Annie Beaudoin, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke; Helene Grassin and John Stewart, Sanofi Canada, Laval, Quebec; and Scot Dowden, Alberta Health Service, Calgary, Alberta, Canada.
Sukhbinder
S
Dhesy-Thind
Sharlene Gill and Malcolm Moore, BC Cancer Agency, Vancouver; Muhammad Zulfiqar, BC Cancer Agency, Abbotsford; Thuan Do, BC Cancer Agency, Surrey; Wendy Yin Han Lam, Burnaby Hospital Cancer Centre, Burnaby, British Columbia; Yoo-Joung Ko, Sunnybrook Health Sciences Centre; Malcolm Moore, Princess Margaret Hospital, Toronto; Christine Cripps, Ottawa Hospital Cancer Centre, Ottawa; Sukhbinder Dhesy-Thind, Juravinski Cancer Centre, Hamilton; Pawel Zalewski, RSM Durham Regional Cancer Centre, Oshawa; Pablo Cano, Sudbury Regional Hospital, Sudbury, Ontario; Annie Beaudoin, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke; Helene Grassin and John Stewart, Sanofi Canada, Laval, Quebec; and Scot Dowden, Alberta Health Service, Calgary, Alberta, Canada.
Muhammad
M
Zulfiqar
Sharlene Gill and Malcolm Moore, BC Cancer Agency, Vancouver; Muhammad Zulfiqar, BC Cancer Agency, Abbotsford; Thuan Do, BC Cancer Agency, Surrey; Wendy Yin Han Lam, Burnaby Hospital Cancer Centre, Burnaby, British Columbia; Yoo-Joung Ko, Sunnybrook Health Sciences Centre; Malcolm Moore, Princess Margaret Hospital, Toronto; Christine Cripps, Ottawa Hospital Cancer Centre, Ottawa; Sukhbinder Dhesy-Thind, Juravinski Cancer Centre, Hamilton; Pawel Zalewski, RSM Durham Regional Cancer Centre, Oshawa; Pablo Cano, Sudbury Regional Hospital, Sudbury, Ontario; Annie Beaudoin, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke; Helene Grassin and John Stewart, Sanofi Canada, Laval, Quebec; and Scot Dowden, Alberta Health Service, Calgary, Alberta, Canada.
Pawel
P
Zalewski
Sharlene Gill and Malcolm Moore, BC Cancer Agency, Vancouver; Muhammad Zulfiqar, BC Cancer Agency, Abbotsford; Thuan Do, BC Cancer Agency, Surrey; Wendy Yin Han Lam, Burnaby Hospital Cancer Centre, Burnaby, British Columbia; Yoo-Joung Ko, Sunnybrook Health Sciences Centre; Malcolm Moore, Princess Margaret Hospital, Toronto; Christine Cripps, Ottawa Hospital Cancer Centre, Ottawa; Sukhbinder Dhesy-Thind, Juravinski Cancer Centre, Hamilton; Pawel Zalewski, RSM Durham Regional Cancer Centre, Oshawa; Pablo Cano, Sudbury Regional Hospital, Sudbury, Ontario; Annie Beaudoin, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke; Helene Grassin and John Stewart, Sanofi Canada, Laval, Quebec; and Scot Dowden, Alberta Health Service, Calgary, Alberta, Canada.
Thuan
T
Do
Sharlene Gill and Malcolm Moore, BC Cancer Agency, Vancouver; Muhammad Zulfiqar, BC Cancer Agency, Abbotsford; Thuan Do, BC Cancer Agency, Surrey; Wendy Yin Han Lam, Burnaby Hospital Cancer Centre, Burnaby, British Columbia; Yoo-Joung Ko, Sunnybrook Health Sciences Centre; Malcolm Moore, Princess Margaret Hospital, Toronto; Christine Cripps, Ottawa Hospital Cancer Centre, Ottawa; Sukhbinder Dhesy-Thind, Juravinski Cancer Centre, Hamilton; Pawel Zalewski, RSM Durham Regional Cancer Centre, Oshawa; Pablo Cano, Sudbury Regional Hospital, Sudbury, Ontario; Annie Beaudoin, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke; Helene Grassin and John Stewart, Sanofi Canada, Laval, Quebec; and Scot Dowden, Alberta Health Service, Calgary, Alberta, Canada.
Pablo
P
Cano
Sharlene Gill and Malcolm Moore, BC Cancer Agency, Vancouver; Muhammad Zulfiqar, BC Cancer Agency, Abbotsford; Thuan Do, BC Cancer Agency, Surrey; Wendy Yin Han Lam, Burnaby Hospital Cancer Centre, Burnaby, British Columbia; Yoo-Joung Ko, Sunnybrook Health Sciences Centre; Malcolm Moore, Princess Margaret Hospital, Toronto; Christine Cripps, Ottawa Hospital Cancer Centre, Ottawa; Sukhbinder Dhesy-Thind, Juravinski Cancer Centre, Hamilton; Pawel Zalewski, RSM Durham Regional Cancer Centre, Oshawa; Pablo Cano, Sudbury Regional Hospital, Sudbury, Ontario; Annie Beaudoin, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke; Helene Grassin and John Stewart, Sanofi Canada, Laval, Quebec; and Scot Dowden, Alberta Health Service, Calgary, Alberta, Canada.
Wendy Yin Han
WYH
Lam
Sharlene Gill and Malcolm Moore, BC Cancer Agency, Vancouver; Muhammad Zulfiqar, BC Cancer Agency, Abbotsford; Thuan Do, BC Cancer Agency, Surrey; Wendy Yin Han Lam, Burnaby Hospital Cancer Centre, Burnaby, British Columbia; Yoo-Joung Ko, Sunnybrook Health Sciences Centre; Malcolm Moore, Princess Margaret Hospital, Toronto; Christine Cripps, Ottawa Hospital Cancer Centre, Ottawa; Sukhbinder Dhesy-Thind, Juravinski Cancer Centre, Hamilton; Pawel Zalewski, RSM Durham Regional Cancer Centre, Oshawa; Pablo Cano, Sudbury Regional Hospital, Sudbury, Ontario; Annie Beaudoin, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke; Helene Grassin and John Stewart, Sanofi Canada, Laval, Quebec; and Scot Dowden, Alberta Health Service, Calgary, Alberta, Canada.
Scot
S
Dowden
Sharlene Gill and Malcolm Moore, BC Cancer Agency, Vancouver; Muhammad Zulfiqar, BC Cancer Agency, Abbotsford; Thuan Do, BC Cancer Agency, Surrey; Wendy Yin Han Lam, Burnaby Hospital Cancer Centre, Burnaby, British Columbia; Yoo-Joung Ko, Sunnybrook Health Sciences Centre; Malcolm Moore, Princess Margaret Hospital, Toronto; Christine Cripps, Ottawa Hospital Cancer Centre, Ottawa; Sukhbinder Dhesy-Thind, Juravinski Cancer Centre, Hamilton; Pawel Zalewski, RSM Durham Regional Cancer Centre, Oshawa; Pablo Cano, Sudbury Regional Hospital, Sudbury, Ontario; Annie Beaudoin, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke; Helene Grassin and John Stewart, Sanofi Canada, Laval, Quebec; and Scot Dowden, Alberta Health Service, Calgary, Alberta, Canada.
Helene
H
Grassin
Sharlene Gill and Malcolm Moore, BC Cancer Agency, Vancouver; Muhammad Zulfiqar, BC Cancer Agency, Abbotsford; Thuan Do, BC Cancer Agency, Surrey; Wendy Yin Han Lam, Burnaby Hospital Cancer Centre, Burnaby, British Columbia; Yoo-Joung Ko, Sunnybrook Health Sciences Centre; Malcolm Moore, Princess Margaret Hospital, Toronto; Christine Cripps, Ottawa Hospital Cancer Centre, Ottawa; Sukhbinder Dhesy-Thind, Juravinski Cancer Centre, Hamilton; Pawel Zalewski, RSM Durham Regional Cancer Centre, Oshawa; Pablo Cano, Sudbury Regional Hospital, Sudbury, Ontario; Annie Beaudoin, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke; Helene Grassin and John Stewart, Sanofi Canada, Laval, Quebec; and Scot Dowden, Alberta Health Service, Calgary, Alberta, Canada.
John
J
Stewart
Sharlene Gill and Malcolm Moore, BC Cancer Agency, Vancouver; Muhammad Zulfiqar, BC Cancer Agency, Abbotsford; Thuan Do, BC Cancer Agency, Surrey; Wendy Yin Han Lam, Burnaby Hospital Cancer Centre, Burnaby, British Columbia; Yoo-Joung Ko, Sunnybrook Health Sciences Centre; Malcolm Moore, Princess Margaret Hospital, Toronto; Christine Cripps, Ottawa Hospital Cancer Centre, Ottawa; Sukhbinder Dhesy-Thind, Juravinski Cancer Centre, Hamilton; Pawel Zalewski, RSM Durham Regional Cancer Centre, Oshawa; Pablo Cano, Sudbury Regional Hospital, Sudbury, Ontario; Annie Beaudoin, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke; Helene Grassin and John Stewart, Sanofi Canada, Laval, Quebec; and Scot Dowden, Alberta Health Service, Calgary, Alberta, Canada.
Malcolm
M
Moore
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D011788:Quality of Life; D000093542:Gemcitabine
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D002955:Leucovorin; D005472:Fluorouracil; D000093542:Gemcitabine