The Randomised Study of Preoperative Radiotherapy With Consolidating Chemotherapy for Unresectable Rectal Cancer

• Overall long-term survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
• Progression-free long-term survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
• The rate of local failures [ Time Frame: 5 years ] [ Designated as safety issue: No ]
• The rate of distant metastases [ Time Frame: 5 years ] [ Designated as safety issue: No ]
• The rate of early toxicity of neoadjuvant treatment according to the NCI CTCAE (version 3.0) [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
• The rate of postoperative complications [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
• The rate of late toxicity according to the RTOG/EORTC scale [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
• The rate of complete pathological response [ Time Frame: Surrogate endpoint available immediatly after surgery ] [ Designated as safety issue: No ]

The addition of Oxaliplatin to conventionally fractionated chemoradiation (FULV or capecitabine) is considered as standard in unresectable rectal cancer by the panel of experts. The Investigators addressed the question whether short-course preoperative radiotherapy with consolidating chemotherapy of FOLFOX4 may increase the rate of R0 resection in patients with unresectable rectal cancer.

Patients with unresectable primary rectal cancer or with unresectable local recurrence without distant metastases are randomly allocated to control or experimental arm. The preoperative treatment in the control arm is conventionally fractionated chemoradiation with 50.4 Gy total dose in 28 fractions of 1.8 Gy over 5.5 weeks simultaneously with 5-Fu, leucovorin and oxaliplatin. Experimental group receive 25 Gy in 5 fractions of 5 Gy over 5 days and after one week interval - consolidating chemotherapy of 3 courses of FOLFOX4. Surgery should be curried out 10-11 weeks from beginning of radiation and at least 4 weeks from the last dose of fluorouracil or radiation. The study hypothesis is that the short-course preoperative radiotherapy with consolidating chemotherapy produce at least 10% increase of the rate of R0 resection compared to preoperative chemoradiation.

• Radiation: Short course of radiotherapy
  5 x 5 Gy and afer one week interval consolidating chemotherapy of 3 courses of FOLFOX4
  Other Names:

  • short radiation
  • consolidating chemotherapy
• Radiation: Radiochemotherapy
  28 x 1,8 Gy with simultaneous neoadjuvant chemotherapy: two courses of 5-Fu 325 mg/m2/day i.v. bolus and LV 20 mg/m2/day i.v.-bolus over 5 days given during 1-5 and 29-33 days of radiation. Oxaliplatin is given 50 mg/m2 once a week 5 times during 1, 8, 15, 22 and 29 days of radiation.
  Other Name: chemoradiation

• Experimental: 1
  25 Gy in 5 fractions of 5 Gy over 5 days. One week interval. Consolidating chemotherapy of 3 courses of FOLFOX4. Surgery 10-11 weeks from beginning of radiation and at least 4 weeks from the last dose of fluorouracil.
  Intervention: Radiation: Short course of radiotherapy
• Active Comparator: 2
  Conventionally fractionated chemoradiation with 50.4 Gy total dose in 28 fractions of 1.8 Gy over 5.5 weeks. Surgery 10-11 weeks from beginning of radiation and at least 4 weeks from the last dose of radiation.
  Intervention: Radiation: Radiochemotherapy

Inclusion Criteria:

• Patients with unresectable primary rectal cancer or with unresectable local recurrence without distant metastases.
• WHO performance status ≤ 2.
• Lower border of tumour ≤ 15 cm from anal verge.

Exclusion Criteria:

• cardiac coronary arterial disease,
• arrhythmias,
• stroke even if they have occurred in the past and are controlled with medication

• Maria Sklodowska-Curie Memorial Cancer Center, Institute of Oncology
• Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Cracow
• Poznan University of Medical Sciences
• Medical University of Lublin