Intensity-modulated radiotherapy (IMRT) and concurrent capecitabine for pancreatic cancer.
OBJECTIVE
Local failure continues to be a major problem in the management of pancreatic cancer. Delivery of adequate radiation doses to the pancreas is limited by radiation-sensitive normal structures in the upper abdomen. To overcome some of these restrictions, we have developed a regimen of intensity-modulated radiotherapy (IMRT) with concurrent capecitabine.


METHODS
This is a retrospective analysis of the first 15 patients with adenocarcinoma of the pancreas treated on this regimen (7 as adjuvant therapy after curative resection and 8 patients for unresectable disease). Intensity-modulated radiotherapy was planned using the CORVUS system and delivered with a segmented multileaf collimator, using a 6-MV photon beam and 10 intensity steps. Two target volumes were entered: target 1 consisted of the gross tumor volume (in unresectable cases) or the tumor bed (in postsurgical cases); and target 2 consisted of the draining lymph nodes. Both targets were treated simultaneously in 25 daily fractions, 5 days a week. In the postoperative setting, the total dose to target 1 was 45-54 Gy (median, 54 Gy). For unresectable disease the dose was 54-55 Gy (median, 54 Gy). The total dose to target 2 was 45 Gy in all patients. Patients were treated with one of two six-field beam arrangements found to produce superior dose distributions. Capecitabine was given at 1,600 mg/m(2)/day in two divided doses, 5 days per week, concurrently with radiotherapy. In addition, most patients (73%) received gemcitabine-based chemotherapy. Systemic chemotherapy was given before, after, or both before and after chemoradiotherapy in 47%, 7%, and 20% of patients, respectively. Patients were evaluated on a weekly basis.


RESULTS
Treatment was tolerated well. Grade 1/2 nausea/vomiting developed in 8 patients (53%) and Grade 1/2 hematologic toxicity developed in 9 patients (60%). Only 1 patient (7%) had Grade 3 toxicity, a gastric ulceration that responded to medical management. Nine patients (60%) had weight loss (median, 7 lbs; range, 3-12 lbs). The median follow-up time is 8.5 months (10.1 months in patients who are alive). In the resectable group there have been no deaths, and there has been 1 local relapse (14%). In the unresectable group there have been 2 deaths, and the 1-year actuarial survival rate is 69%. Two patients converted to resectability, 5 patients (62.5%) have persistent locoregional disease after chemoradiotherapy, and 1 patient (12%) is locally controlled without surgery.


CONCLUSIONS
This regimen of IMRT with tumor-selective radiosensitization is well tolerated. The low toxicity profile compares favorably with that of protocols based on continuous-infusion 5-fluorouracil or gemcitabine, and the preliminary indications of efficacy are encouraging.
Ben-Josef
Edgar
E
Department of Radiation Oncology, Wayne State University and the Karmanos Cancer Institute, Detroit, MI, USA. edgarb@med.umich.edu
Shields
Anthony F
AF
Vaishampayan
Ulka
U
Vaitkevicius
Vainutis
V
El-Rayes
Basil F
BF
McDermott
Patrick
P
Burmeister
Jay
J
Bossenberger
Todd
T
Philip
Philip A
PA
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000069287:Capecitabine; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D011355:Prodrugs / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods*; D012189:Retrospective Studies; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D011355:Prodrugs; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil; D000093542:Gemcitabine