Full-dose gemcitabine with concurrent radiation therapy in patients with nonmetastatic pancreatic cancer: a multicenter phase II trial.
OBJECTIVE
Gemcitabine is effective in the treatment of pancreatic cancer and is a potent radiosensitizer. This study assessed safety and efficacy of full-dose gemcitabine administered before and during concurrent three-dimensional conformal radiation (3D-CRT) in patients with nonmetastatic pancreatic cancer.


METHODS
During cycles 1 and 3, patients received gemcitabine at 1,000 mg/m(2) on days 1 and 8 of each 21-day cycle. Cycle 2 included the same dose of gemcitabine on days 1, 8, and 15 of a 28-day cycle with concurrent 3D-CRT at 36 Gy, administered in 15 fractions of 2.4 Gy, over 3 weeks. Resectable patients underwent surgery 4 to 6 weeks after treatment. The primary objective was evaluation of toxicity. Tumor response, CA 19-9, and 1-year survival were also assessed.


RESULTS
Forty-one patients enrolled at six institutions between April 2002 and October 2003. Among the 39 treated patients, the most common toxicities were grade 3 neutropenia (12.8%), grade 3 nausea (10.3%), and grade 3 vomiting (10.3%). The response rate was 5.1% and disease control rate was 84.6%. Mean post-treatment CA 19-9 levels (228 +/- 347 U/mL) were significantly (P = .006) reduced compared with pretreatment levels (1,241 +/- 2,124 U/mL). Thirteen (81%) of 16 patients initially judged resectable, three (33%) of nine borderline-resectable patients, and one (7%) of 14 unresectable patients underwent resection after therapy. One-year survival rates were 73% for all patients, 94% for resectable patients, 76% for borderline-resectable patients, and 47% for unresectable patients.


CONCLUSIONS
Full-dose gemcitabine with concurrent radiotherapy was well tolerated and active. Evaluation of this regimen in a larger, randomized trial for patients with resectable or borderline-resectable disease may be warranted.
Small
William
W
Robert H. Lurie Comprehensive Cancer Center of Northwestern University, 251 East Huron St, LC-178, Chicago, IL 60611, USA. wsmall@nmff.org
Berlin
Jordan
J
Freedman
Gary M
GM
Lawrence
Theodore
T
Talamonti
Mark S
MS
Mulcahy
Mary F
MF
Chakravarthy
A Bapsi
AB
Konski
Andre A
AA
Zalupski
Mark M
MM
Philip
Philip A
PA
Kinsella
Timothy J
TJ
Merchant
Nipun B
NB
Hoffman
John P
JP
Benson
Al B
AB
Nicol
Steven
S
Xu
Rong M
RM
Gill
John F
JF
McGinn
Cornelius J
CJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D018395:CA-19-9 Antigen / Q000097:blood; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D018714:Radiotherapy, Adjuvant; D020266:Radiotherapy, Conformal; D016019:Survival Analysis; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D003841:Deoxycytidine; D000093542:Gemcitabine