Docetaxel/Gemcitabine followed by gemcitabine and external beam radiotherapy in patients with pancreatic adenocarcinoma.
BACKGROUND
Pancreatic cancer remains highly lethal. Previous attempts with neoadjuvant therapy in this disease have been inconclusive, but a potential for benefit exists. We conducted a phase II trial of dose-intense docetaxel and gemcitabine followed by twice-weekly gemcitabine and external beam radiotherapy in patients with pancreatic adenocarcinoma.


METHODS
Patients with stage I to III disease were eligible. Docetaxel 65 mg/m(2) intravenously over 1 hour and gemcitabine 4000 mg/m(2) given intravenously over 30 minutes were given on days 1, 15, and 29. On day 43, radiotherapy was begun at 50.4 Gy with gemcitabine 50 mg/m(2) intravenously over 30 minutes twice weekly for 12 doses. After treatment, patients were considered for resection.


RESULTS
Twenty-four assessable patients were recruited onto the trial. All but one patient completed a full 12 weeks of therapy. Grade 3 and 4 hematological and nonhematological toxicities were common but manageable, and neutropenic fever did not occur. No patient had local tumor progression. Twelve patients (50%) responded by Response Evaluation Criteria in Solid Tumors Group (RECIST) criteria, including one radiographic complete response. Seventeen patients underwent resection after therapy. Margin-negative resections were performed in 13 patients, including 9 patients whose disease was borderline or unresectable before treatment. A treatment effect was seen in all resection specimens. There have been no local recurrences of tumor, and several patients remain alive without evidence of disease.


CONCLUSIONS
Docetaxel/gemcitabine followed by gemcitabine/radiotherapy is active in the treatment of pancreatic adenocarcinoma, with manageable toxicity. Tumor downstaging occurs in some patients to allow complete resection. Further investigation of this regimen is warranted.
Pipas
J Marc
JM
Gastrointestinal Oncology Program, Dartmouth-Hitchcock Medical Center/Norris Cotton Cancer Center, One Medical Center Drive, Lebanon, NH 03756, USA. j.marc.pipas@hitchcock.org
Barth
Richard J
RJ
Zaki
Bassem
B
Tsapakos
Michael J
MJ
Suriawinata
Arief A
AA
Bettmann
Michael A
MA
Cates
Justin M
JM
Ripple
Gregory H
GH
Sutton
John E
JE
Gordon
Stuart R
SR
McDonnell
Carol E
CE
Perez
Raymond P
RP
Redfield
Nancy
N
Meyer
Louise P
LP
Marshall
John F
JF
Cole
Bernard F
BF
Colacchio
Thomas A
TA
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077143:Docetaxel; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D020266:Radiotherapy, Conformal; D043823:Taxoids / Q000008:administration & dosage*; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000093542:Gemcitabine