Phase I study of preoperative radiation therapy with concurrent infusional 5-fluorouracil and oxaliplatin followed by surgery and postoperative 5-fluorouracil plus leucovorin for T3/T4 rectal adenocarcinoma: ECOG E1297.

Abstract

PURPOSE:

Oxaliplatin is a platinum analog and radiosensitizer active in colorectal cancer. We performed a Phase I trial to test the safety and preliminary efficacy of adding oxaliplatin to standard preoperative chemoradiation therapy for rectal cancer.

METHODS AND MATERIALS:

Eligible patients had T3 to T4 rectal adenocarcinoma. Patients received standard-dose radiation (50.4 Gy for 5.5 weeks) with concurrent infused 5-fluorouracil (5-FU) at 200 mg/m2 per day, 7 days per week. Oxaliplatin was given three times at 14-day intervals at 55, 70, or 85 mg/m2 during the 5.5-week radiation period, before resection. Adjuvant therapy consisted of four cycles of 5-FU (500 mg/m2 per week) with leucovorin (500 mg/m2 per week) given every 6 weeks. The main goals were to identify the maximum tolerated dose of oxaliplatin and the dose-limiting toxicities when given with 5-FU and RT. Secondary goals were to determine resectability, pathologic response, sphincter preservation, and overall survival rates.

RESULTS:

Twenty-one patients were enrolled, 5 at the 55 mg/m2 oxaliplatin dose level, 5 at 70 mg/m2, and 11 at 85 mg/m2. All patients were able to complete the preoperative chemoradiation regimen with no dose adjustments. No dose-limiting toxicities or differences in the type or extent of toxicity were noted among the groups. Nineteen patients underwent surgery (three abdominopelvic resections and 16 low anterior resections), for an 84% sphincter preservation rate. The pathologic complete response rate was 26% (5 patients), and minimal microscopic residual tumor was found in 21% (4 additional patients).

CONCLUSIONS:

Oxaliplatin was well tolerated at 85 mg/m2 given every 2 weeks in combination with standard preoperative chemoradiation for rectal cancer. The rates of major pathologic response and sphincter preservation are promising.

• Authors: David I Rosenthal, Paul J Catalano, Daniel G Haller, Jerome C Landry, Elin R Sigurdson, Francis R Spitz, Al B Benson 3rd
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 72 Issue 1 Pg. 108-13 (Sep 01 2008) ISSN: 0360-3016 [Print] United States
• PMID: 18722265 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Organoplatinum Compounds
• Radiation-Sensitizing Agents
• Oxaliplatin
• Leucovorin
• Fluorouracil

Topics

• Adenocarcinoma (pathology, surgery, therapy)
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Combined Modality Therapy (methods)
• Female
• Fluorouracil (administration & dosage, adverse effects)
• Humans
• Leucovorin (administration & dosage, adverse effects)
• Male
• Middle Aged
• Neoplasm Staging
• Neoplasm, Residual (therapy)
• Organoplatinum Compounds (administration & dosage, adverse effects)
• Oxaliplatin
• Radiation-Sensitizing Agents (administration & dosage, adverse effects)
• Rectal Neoplasms (pathology, surgery, therapy)