Phase I trial of preoperative hypofractionated intensity-modulated radiotherapy with incorporated boost and oral capecitabine in locally advanced rectal cancer.
OBJECTIVE
To determine the safety and efficacy of preoperative hypofractionated radiotherapy using intensity-modulated radiotherapy (IMRT) and an incorporated boost with concurrent capecitabine in patients with locally advanced rectal cancer.


METHODS
The eligibility criteria included adenocarcinoma of the rectum, T3-T4 and/or N1-N2 disease, performance status 0 or 1, and age > or =18 years. Photon IMRT and an incorporated boost were used to treat the whole pelvis to 45 Gy and the gross tumor volume plus 2 cm to 55 Gy in 25 treatments within 5 weeks. The study was designed to escalate the dose to the gross tumor volume in 5-Gy increments in 3-patient cohorts. Capecitabine was given orally 825 mg/m(2) twice daily for 7 days each week during RT. The primary endpoint was the maximal tolerated radiation dose, and the secondary endpoints were the pathologic response and quality of life.


RESULTS
Eight patients completed RT at the initial dose level of 55 Gy. The study was discontinued because of toxicity-six Grade 3 toxicities occurred in 3 (38%) of 8 patients. All patients went on to definitive surgical resection, and no patient had a pathologically complete response.


CONCLUSIONS
This regimen, using hypofractionated RT with an incorporated boost, had unacceptable toxicity despite using standard doses of capecitabine and IMRT. Additional research is needed to determine whether IMRT is able to reduce the side effects during and after pelvic RT with conventional dose fractionation.
Freedman
Gary M
GM
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA 19111, USA. G_Freedman@FCCC.edu
Meropol
Neal J
NJ
Sigurdson
Elin R
ER
Hoffman
John
J
Callahan
Elaine
E
Price
Robert
R
Cheng
Jonathan
J
Cohen
Steve
S
Lewis
Nancy
N
Watkins-Bruner
Deborah
D
Rogatko
André
A
Konski
Andre
A
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D003131:Combined Modality Therapy / Q000379:methods; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019583:Dose Fractionation, Radiation; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007432:Intraoperative Period; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D017785:Photons / Q000627:therapeutic use; D011788:Quality of Life; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects* / Q000379:methods; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil