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rectal cancerNeOadjuVaNt chemOradiatiON

Elena Tsvetkova, MD, FRCPC, medical Oncologist, juravinski cancer centre, hamilton

TRial suMMaRy: short-course radiation followed by FOlFOX Bujko K. Neodadjuvant chemoradiation for fixed ct3 or t4 rectal cancer: results of a Polish multicentre phase 3 study. J Clin Oncol 2016; 34(suppl 4S; abstract 489).

This multicentre phase 3 trial tested the efficacy, in patients with “unresectable” rectal cancer, of preoperative radiation therapy of 25 Gy in 5 fractions followed by consolidation chemotherapy with 3 courses of FOLFOX4 (5-fluorouracil [5FU] bolus, leucovorin and oxaliplatin) in the investiga-tional arm vs a control arm receiving standard neoadjuvant chemoradiation (50.4 gy delivered in 28 fractions given simultaneously with FOLFOX4). Patients with fixed cT3 or T4 rectal cancer without distant metastases were random-ized to experimental or control arms. For the second part of the study, oxaliplatin was delivered to 2 groups at the discretion of the participating centre. Surgery was sched-uled about 6 weeks after completion of neoadjuvant treat-ment (12 weeks after starting radiation). A total of 515

patients were eligible for analysis; of these, 261 patients were treated in the experimental arm.

Results: Acute toxicity was observed in 74% of patients in the experimental arm and in 83% of patients in the con-trol arm (p=0.007). The rate of grade 3+ toxicities was equal in both arms, at 24%. R0 resection (a primary end-point) and pathologic complete response rates in the exper-imental and control arms were 77% vs 71% (p=0.081) and 16% vs 11.5% (p=0.19), respectively. Median followup was 35 months. At 3 years, rates of OS, disease-free survival (DFS), and cumulative incidence of local failure were, in the experimental arm and control arm respectively, 72% vs 64.5% (p=0.055), 53% vs 53% (p=0.74), and 22% vs 21% (p=0.82). The trial demonstrated no difference between a short course of radiation followed by consolidation chemo-therapy, and standard neoadjuvant chemoradiation. There was a trend toward improved OS, lower toxicity, lower cost and greater convenience observed in the experimental arm employing a short course of radiation and consolidation chemotherapy.

COMMEnTaRy: The standard treatment for patients with locally advanced rectal cancer has been concurrent chemo-radiation followed by surgery and chemotherapy. This Polish phase III study presents another viable treatment option for this patient population. Five hundred and fifteen patients with primary unresectable fixed cT3-T4 rectal cancer were randomized to short-course radiation (investigational arm) or standard chemoradiation (control arm). Chemotherapy employed in the control arm was FOLFOX 4; the same chemotherapy was used in the investigational arm after a

short course of radiation. However, FOLFOX chemothera-py has not been considered a standard therapy in the con-current chemotherapy setting, as it has greater toxicity than 5FU and leucovorin given concurrently with radiation. Patients in both arms underwent surgery 12 weeks after starting radiation therapy. The rate of acute toxicity was 74% in the radiation arm and 83% in the concurrent chemoradiation arm, with major toxicities such as diarrhea, inflammation of the bladder and rectum, and local cutane-ous radiation reaction. At 3 years, DFS and OS in the

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experimental arm were 53% vs 52% and 73% vs 63.5%, respectively. This trial demonstrated equal efficacy of 2 regimens, with fewer adverse effects in the group receiving a short course of radiation followed by consolidation chemoradiation; patients were able to gain earlier exposure to systemic therapy to control micrometastatic disease. However, the chemotherapy regimen (FOLFOX4) employed in the control arm was not a standard one used in the majority of centres in North America. Even though grade 3+ toxicities were equal in both arms, the rate of all-grade toxicities was significantly higher in the experimental arm. No information was provided on lymph node status. Long-term followup results would be beneficial.

In BrIEFalready known• Standard treatment for patients with locally

advanced rectal cancer involves concurrent chemo-radiation followed by surgery and chemotherapy.

• FOLFOX chemotherapy has not been used along-side radiation as it has greater toxicity than 5Fu and leucovorin in this context.

What this study showed• Short-course radiation followed by FOLFOX was

equally effective to standard therapy and produced fewer side effects.

next steps• Being aware that the FOLFOX4 regimen used in this

Polish study is not the same as that used in most North american centres, investigate the poten-tial for short-course radiation and consolidation chemoradiation.