A phase I trial of preoperative S-1 in combination with oxaliplatin and pelvic radiation for lower rectal cancer with T4 and lateral pelvic lymph node metastasis.
BACKGROUND
The purpose of this phase I study of the dose escalation of oxaliplatin in combination with oral S-1 and pelvic radiation preoperatively for poor-risk lower rectal cancer was to determine the dose-limiting toxicity (DLT) and recommended dose of oxaliplatin.


METHODS
Patients with cT4 and lateral pelvic lymph node metastasis, and without distant metastasis (cM0), were treated with weekly oxaliplatin, oral S-1 40 mg/m(2) twice daily for 5 days a week, and radiation. A total of 5 weekly doses of oxaliplatin were planned. RT was administered to a total dose of 50.4 Gy in 28 fractions.


RESULTS
We enrolled 11 patients between December 2009 and January 2012. DLTs were observed at dose level 1 (50 mg/m(2)) in two patients, one of whom experienced grade 3 aspartate aminotransferase elevation and a grade 3 alanine aminotransferase increase, and the other developed grade 4 hypokalemia and a grade 3 alanine aminotransferase increase. Five patients at dose level 2 (60 mg/m(2)) showed no DLTs. The hematological toxicities in all patients were mild and reversible. One patient showed distant metastasis after chemoradiation. Ten of the 11 patients achieved R0 resection by mesorectal resection and lateral lymph node dissection; three of the 10 underwent combined resection of the other organs.


CONCLUSIONS
This phase I trial of preoperative S-1 in combination with oxaliplatin and radiation for lower rectal cancer with T4 and lateral pelvic lymph node metastasis revealed that the recommended dose of oxaliplatin was 60 mg/m(2) weekly.
Division of Colon and Rectal Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Higashinari-ku, Osaka, 537-8511, Japan, ohue-ma@mc.pref.osaka.jp.
Masayuki
M
Ohue
Tetsuya
T
Hamaguchi
Yoshinori
Y
Ito
Daisuke
D
Sakai
Shingo
S
Noura
Yusuke
Y
Kinugasa
Shin
S
Fujita
Yasuhiro
Y
Shimada
Norio
N
Saito
Yoshihiro
Y
Moriya
D000230:Adenocarcinoma / Q000556:secondary / Q000628:therapy*; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D059186:Chemoradiotherapy, Adjuvant / Q000009:adverse effects; D003967:Diarrhea / Q000139:chemically induced; D019583:Dose Fractionation, Radiation; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects*; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D010388:Pelvis; D011300:Preoperative Care; D012004:Rectal Neoplasms / Q000473:pathology / Q000628:therapy*; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D014839:Vomiting / Q000139:chemically induced
D004338:Drug Combinations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase