Phase I study of twice-weekly gemcitabine and concomitant external-beam radiotherapy in patients with adenocarcinoma of the pancreas.
OBJECTIVE
To determine the maximum tolerated dose and dose-limiting toxicity associated with twice-weekly gemcitabine and concomitant external-beam radiotherapy in patients with adenocarcinoma of the pancreas.


METHODS
Twenty-one patients with biopsy-proven adenocarcinoma of the pancreas were treated with external-beam radiotherapy to a dose of 50.4 Gy in 28 fractions, concurrent with gemcitabine, infused over 30 min before irradiation on a Monday and Thursday schedule. The dose of gemcitabine was escalated in 5 cohorts of 3--6 patients each. Initial gemcitabine dose was 10 mg/m(2), with dose escalation until dose-limiting toxicity was observed.


RESULTS
The maximum tolerated dose of gemcitabine was 50 mg/m(2), when given in a twice-weekly schedule with radiation. Dose-limiting toxicity was seen in 2 patients at 60 mg/m(2), and consisted of severe upper gastrointestinal bleeding approximately 1 month after completion of treatment. Six patients had radiographic evidence of response to treatment, and 5 of these underwent complete surgical resection. Three patients who underwent complete resection had been deemed to have unresectable tumors before enrollment on trial. Four patients are alive, including 2 without evidence of disease more than 1 year after resection.


CONCLUSIONS
The combination of external-beam radiation and twice-weekly gemcitabine at a dose of 50 mg/m(2) is well tolerated and shows promising activity for the treatment of pancreatic cancer. Our data suggest a higher maximum tolerated dose and different dose-limiting toxicity than previously reported. Further investigation of this regimen is warranted.
Pipas
J M
JM
Dartmouth Hitchcock Medical Center/Norris Cotton Cancer Center, Lebanon, NH 03756, USA. j.marc.pipas@hitchcock.org
Mitchell
S E
SE
Barth
R J
RJ
Vera-Gimon
R
R
Rathmann
J
J
Meyer
L P
LP
Wagman
R S
RS
Lewis
L D
LD
McDonnell
C
C
Colacchio
T A
TA
Perez
R P
RP
D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001855:Bone Marrow Diseases / Q000209:etiology; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005221:Fatigue / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006471:Gastrointestinal Hemorrhage / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000209:etiology; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D011882:Radiotherapy, High-Energy / Q000009:adverse effects; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine