Chemoradiotherapy in patients with pancreatic carcinoma: phase-I study with a fixed radiation dose and escalating doses of weekly gemcitabine.
OBJECTIVE
The aim of this phase-I study is to determine the maximum tolerated dose (MTD) of weekly gemcitabine in concurrent combination with a total radiation dose of 54 Gy in patients with pancreatic cancer.


METHODS
In all patients, a total dose of 54 Gy was delivered in 30 fractions of 1.8 Gy/day. Gross tumor volume and regional lymph nodes were included in the irradiated volume with a 1- to 1.5-cm margin. The doses of weekly gemcitabine were escalated from 100 mg/m2 by increments of 50 mg/m2. Dose-limiting toxicity (DLT) was defined as hematologic toxicity, prolonged grade-3 non-hematologic toxicity, and incompletion of the planned treatment.


RESULTS
Twenty-six patients entered the trial. From level 1 (100 mg/m2) to level 4 (250 mg/m2), no patient experienced DLT except for 1 patient at level 1. At level 5 (300 mg/m2), 3 of the 5 patients met the DLT criteria. One patient developed severe pulmonary abscess, and the other 2 patients had hematologic DLT. The overall partial response rate was 29%, and the median survival time was 13.7 months. The first relapse occurred at the in-field primary site in 6 patients and at distant organs in 13 patients.


CONCLUSIONS
The MTD of weekly gemcitabine was 250 mg/m2 in the present chemoradiotherapy setting. The efficacy of this chemoradiotherapy regimen is currently being evaluated in the phase-II setting.
Oya
Natsuo
N
Department of Therapeutic Radiology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. n-oya@kaiju.medic.kumamoto-u.ac.jp
Shibuya
Keiko
K
Sakamoto
Takashi
T
Mizowaki
Takashi
T
Doi
Ryuichiro
R
Fujimoto
Koji
K
Imamura
Masayuki
M
Nagata
Yasushi
Y
Hiraoka
Masahiro
M
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001772:Blood Cell Count; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D013534:Survival; D000093542:Gemcitabine
D000903:Antibiotics, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine