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.

Abstract

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.

CONCLUSION:

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.

• Authors: Masayuki Ohue, Tetsuya Hamaguchi, Yoshinori Ito, Daisuke Sakai, Shingo Noura, Yusuke Kinugasa, Shin Fujita, Yasuhiro Shimada, Norio Saito, Yoshihiro Moriya
• Journal: International journal of clinical oncology (Int J Clin Oncol) Vol. 20 Issue 2 Pg. 338-44 (Apr 2015) ISSN: 1437-7772 [Electronic] Japan
• PMID: 24839048 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Drug Combinations
• Organoplatinum Compounds
• Oxaliplatin
• S 1 (combination)
• Tegafur
• Oxonic Acid
• Aspartate Aminotransferases
• Alanine Transaminase

Topics

• Adenocarcinoma (secondary, therapy)
• Adult
• Aged
• Alanine Transaminase (blood)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Aspartate Aminotransferases (blood)
• Chemoradiotherapy, Adjuvant (adverse effects)
• Diarrhea (chemically induced)
• Dose Fractionation, Radiation
• Drug Combinations
• Female
• Humans
• Lymph Node Excision
• Lymphatic Metastasis
• Male
• Middle Aged
• Neoadjuvant Therapy (adverse effects)
• Neoplasm Staging
• Neutropenia (chemically induced)
• Organoplatinum Compounds (administration & dosage, adverse effects)
• Oxaliplatin
• Oxonic Acid (administration & dosage, adverse effects)
• Pelvis
• Preoperative Care
• Rectal Neoplasms (pathology, therapy)
• Tegafur (administration & dosage, adverse effects)
• Vomiting (chemically induced)