Multicenter dose-finding study of concurrent capecitabine and radiotherapy as adjuvant treatment for operable rectal cancer.
OBJECTIVE
5-Fluorouracil-based chemotherapy with concurrent radiotherapy (RT) is the standard adjuvant treatment in rectal cancer. A Phase I study was conducted to determine the maximal tolerated dose and the dose-limiting toxicities of capecitabine combined with standard RT as adjuvant treatment in patients with rectal cancer.


METHODS
Patients with Stage II-III rectal cancer after surgery were eligible. RT included a total dose of 50.4 Gy in fractions of 1.8 Gy/d, 5 d/wk, for 5.5 weeks. Capecitabine was administered twice daily in escalating doses during the entire period of RT. Dose-limiting toxicity included Grade 4 neutropenia or thrombocytopenia, febrile neutropenia, Grade 3 or greater nonhematologic toxicity, or treatment delay because of unresolved toxicity for >1 week.


RESULTS
Thirty-one patients were enrolled at the following dose levels: 1000 mg/m(2)/d (3 patients), 1150 mg/m(2)/d (4 patients) 1300 mg/m(2)/d (6 patients), 1400 mg/m(2)/d (6 patients), 1500 mg/m(2)/d (3 patients), 1600 mg/m(2)/d (3 patients), and 1700 mg/m(2)/d (6 patients). Dose-limiting toxicities were observed in 2 patients at 1300 mg/m(2)/d (Grade 3 diarrhea), and 2 patients at 1400 mg/m(2)/d (skin toxicity in 1 and abdominal pain with fever in 1, resulting in treatment delay), and 3 patients at 1700 mg/m(2)/d (2 patients had Grade 3 diarrhea and 1 had hand-foot syndrome). Four patients presented with chronic postradiation colitis.


CONCLUSIONS
The maximal tolerated dose of capecitabine given concurrently with RT was 1600 mg/m(2)/d in this study. This dose is recommended for additional use in Phase II-III studies.
Souglakos
John
J
Department of Medical Oncology, School of Medicine, University General Hospital of Heraklion, Crete, Greece.
Androulakis
Nikolaos
N
Mavroudis
Dimitrios
D
Kourousis
Charalabos
C
Kakolyris
Stylianos
S
Vardakis
Nikolaos
N
Kalbakis
Konstantinos
K
Pallis
Athanasios
A
Ardavanis
Alexandros
A
Varveris
Charalabos
C
Georgoulias
Vassilios
V
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000069287:Capecitabine; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D012004:Rectal Neoplasms / Q000628:therapy*
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil