A phase I trial of intravenous bromodeoxyuridine and radiation therapy for pancreatic cancer.
OBJECTIVE
Improved radiosensitization may lead to improved results of treatment for pancreatic cancer. This Phase I trial was designed to determine the maximum tolerable dose of intravenous bromodeoxyuridine (BrdUrd) when given in an alternating weekly fashion with radiation therapy for patients with pancreatic cancer.


METHODS
Patients with resected or locally unresectable pancreatic cancer were eligible if distant metastases were not present. A continuous intravenous infusion of BrdUrd was given on weeks 1, 3, 5, and 7. Twice a day radiation therapy (1.5 Gy per fraction) was given on weeks 2, 4, 6, and 8 to the pancreas/pancreatic bed (total dose 60 Gy) and draining regional lymph nodes (total dose 45 Gy). The starting dose of BrdUrd was 800 mg/m2/day with a planned escalation to 1000 mg/m2/day if at least six out of eight patients were without Grade > or = 3 toxicity. Patients were assessed weekly for toxicity, and were followed every 3 months after treatment for complications and survival.


RESULTS
Fifteen patients with resected (six) or unresectable (nine) pancreatic cancer were enrolled. One patient failed to complete therapy due to tumor progression. One of 11 patients treated with 800 mg/m2/day had a Grade 3 toxicity, while Grade 3 or 4 toxicity was found in all 3 patients receiving 1000 mg/m2/day. The dose-limiting toxicities were hematologic. The acute gastrointestinal toxicity was minimal. Two patients, including one with unresectable disease, were without evidence of disease during exploration for complications (ulcer, small bowel obstruction).


CONCLUSIONS
The recommended dose of BrdUrd for Phase II study is 800 mg/m2/day. The gastrointestinal mucosa did not appear to be sensitized by this method of BrdUrd administration. The presence of a pathologic complete response is encouraging. Further improvements in radiosensitization are possible and may lead to improved local control.
Robertson
J M
JM
Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48073, USA.
Ensminger
W D
WD
Walker
S
S
Lawrence
T S
TS
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D001973:Bromodeoxyuridine / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D011879:Radiotherapy Dosage
D000964:Antimetabolites, Antineoplastic; D001973:Bromodeoxyuridine