Final safety findings from a randomized phase III trial of preoperative FU-based chemoradiation +/- weekly oxaliplatin as neoadjuvant therapy for patients with locally advanced rectal cancer: the STAR (Studio Terapia Adiuvante Retto)-01 randomized trial

Reviewer: Christine Hill, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: February 7, 2009

Presenter: C. Aschele on behalf of STAR Network Investigators


  • Beginning in the mid-1990s, with the publication of results from the German CAO/ARO/AIO 94 trial, a paradigm shift from treatment of locally advanced rectal cancer with up-front surgery to administration of preoperative chemoradiotherapy took place. This change was based on demonstrated improvement in colostomy-free survival with administration of neoadjuvant chemoradiotherapy.
  • Since that time, numerous questions regarding optimal chemotherapy drugs, radiotherapy dose and fractionation, and combined-modality approaches have ensued.
  • Weekly oxaliplatin used in combination with 5FU and radiotherapy has been demonstrated to have promising local activity in treatment of rectal cancers (Ann Oncol, 2005).
  • The study presented here was undertaken in order to definitively evaluate the safety of oxaliplatin in combination with 5FU and pelvic radiotherapy for patients with locally advanced rectal cancers.


  • Eligibility criteria included biopsy-proven resectable adenocarcinoma of the mid-low rectum (within 12 cm from the anal verge), with radiologic evidence of perirectal fat or regional nodal involvement.
  • Patients were randomized to one of two arms:
    • Arm A:
      • Continuous infusion 5FU, 225 mg/msq[v1] /day.
      • Concomitant external-beam pelvic radiation delivered in 1.8 Gy fractions to a total dose of 50.4 Gy.
    • Arm B:
      • Continuous infusion 5FU, 225 mg/msq/day.
      • Concomitant external-beam pelvic radiation delivered in 1.8 Gy fractions to a total dose of 50.4 Gy.
      • Concomitant oxaliplatin, 60 mg/msq, on the first day of each treatment week for a total of 6 doses.
  • Total mesorectal excision surgery was planned for 6-8 weeks after completion of chemoradiotherapy for both arms.
  • Accrual target was 690 patients.


  • A total of 752 patients from 40 centers were eligible and randomized between December 2003 and August 2008.
  • 734 of these were evaluable for safety and toxicity.
  • The total rate of grade 3-4 toxicity was 8% in Arm A, and 23% in Arm B.
    • Grade 3-4 nausea occurred in 0 patients in Arm A, and 2% in Arm B (p < 0.05), and any nausea occurred in 18% of patients in Arm A, and 39% in Arm B.
    • Vomiting was experienced by 5% of Arm A patients, and 25% of Arm B patients, with no significant difference in incidence of grade 3-4 vomiting between the two arms.
    • Grade 3-4 diarrhea occurred in 4% patients in Arm A, and 15% in Arm B (p < 0.05), and any diarrhea occurred in 49% of patients in Arm A, and 64% in Arm B.
    • Incidence of grade 3-4 dermatitis was significantly higher in Arm B (4% versus 2% in Arm A, p < 0.05).
    • No difference was apparent in incidence of stomatitis, leucopenia, thrombocytopenia, or neurosensory toxicity between the two arms.
  • All-cause mortality before surgery was 0.3% in Arm A, and 1% in Arm B (p = NS).
  • 90% of planned radiotherapy was delivered to 94% of patients in Arm A, and 89% of those in Arm B (p = NS).
  • Median time to surgery from completion of chemoradiation was 51 days for patients in Arm A, and 52 days for those in Arm B (p = NS).

Authors’ conclusions

  • The authors conclude that the addition of oxaliplatin to 5FU-based preoperative chemoradiation for rectal cancer is feasible without major unexpected adverse events.
  • They note that addition of oxaliplatin appears to significantly increase the incidence of grade 3-4 toxicity, but that ability to deliver planned radiotherapy and perform planned surgical excision were not impacted.


  • Although the data presented here are interesting in and of itself, this study will become even more important when outcomes data are reported. The authors note that outcome information, albeit with relatively short follow-up, will be made available later in 2009. As the data mature, this study will represent a well-done, randomized comparison between two widely used chemoradiotherapy regimens for neoadjuvant treatment of locally advanced rectal cancer.
  • As the authors note, although the addition of oxaliplatin does appear to increase grade 3-4 toxicity, it did not impact delivery of radiotherapy or time to planned surgery in this trial.
  • Should the addition of oxaliplatin result in improved outcomes, its addition to neoadjuvant rectal cancer regimens would likely prove beneficial despite increased toxicity. Excellent medical support of patients undergoing treatment would likely gain further importance in this scenario.
  • This study represents further, more complete evaluation of the addition of oxaliplatin to rectal cancer regimens in a phase III setting. The data presented here confirms data from other phase I trials evaluating feasibility and safety of this approach (Rosenthal, IJROBP, 2008). Data on local control and survival will be of great interest to the oncologic community.