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

Conditions

Rectal Cancer

Keywords

Rectal cancer, Preoperative radiotherapy and consolidating chemotherapy

Brief summary

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.

Detailed description

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.

Mariola Winiarek, Katarzyna Marcisz-Grzanka, Lucjan Wyrwicz

Journal of Clinical Oncology2025-01-27

10.1200/jco.2025.43.4_suppl.84

A multicenter, randomized, phase III trial of short-term radiotherapy plus chemotherapy versus long-term chemoradiotherapy in locally advanced rectal cancer (STELLAR): The final reports.

Jing Jin, Yuan Tang, Chen Hu, Yong Cai, Yuan Zhu et al. (20 authors)

Journal of Clinical Oncology2021-05-2039 citations

10.1200/jco.2021.39.15_suppl.3510

Long-course preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for clinical T4 and fixed clinical T3 rectal cancer: long-term results of the randomized Polish II study.

Ciseł B, Pietrzak L, Michalski W, Wyrwicz L, Rutkowski A, Kosakowska E, Cencelewicz A, Spałek M, Polkowski W, Jankiewicz M, Styliński R, Bębenek M, Kapturkiewicz B, Maciejczyk A, Sadowski J, Zygulska J, Zegarski W, Jankowski M, Las-Jankowska M, Toczko Z, Żelazowska-Omiotek U, Kępka L, Socha J, Wasilewska-Tesluk E, Markiewicz W, Kładny J, Majewski A, Kapuściński W, Suwiński R, Bujko K, Polish Colorectal Study Group.

2019-08-01199 citations

10.1093/annonc/mdz186

Cost-effectiveness analysis of long-course oxaliplatin and bolus of fluorouracil based preoperative chemoradiotherapy vs. 5x5Gy radiation plus FOLFOX4 for locally advanced resectable rectal cancer.

Wang S, Wen F, Zhang P, Wang X, Li Q.

2019-06-2415 citations

10.1186/s13014-019-1319-8

Effect of sex on treatment outcomes in rectal cancer patients after neoadjuvant radiotherapy or chemoradiation: A combined analysis of Polish-1 and Polish-2 studies.

Lucjan Wyrwicz, Mateusz Spałek, Wojciech Michalski, J Kryński, Wojciech Polkowski et al. (6 authors)

Journal of Clinical Oncology2017-02-01

10.1200/jco.2017.35.4_suppl.656

Long-course oxaliplatin-based preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study.

Bujko K, Wyrwicz L, Rutkowski A, Malinowska M, Pietrzak L, Kryński J, Michalski W, Olędzki J, Kuśnierz J, Zając L, Bednarczyk M, Szczepkowski M, Tarnowski W, Kosakowska E, Zwoliński J, Winiarek M, Wiśniowska K, Partycki M, Bęczkowska K, Polkowski W, Styliński R, Wierzbicki R, Bury P, Jankiewicz M, Paprota K, Lewicka M, Ciseł B, Skórzewska M, Mielko J, Bębenek M, Maciejczyk A, Kapturkiewicz B, Dybko A, Hajac Ł, Wojnar A, Leśniak T, Zygulska J, Jantner D, Chudyba E, Zegarski W, Las-Jankowska M, Jankowski M, Kołodziejski L, Radkowski A, Żelazowska-Omiotek U, Czeremszyńska B, Kępka L, Kolb-Sielecki J, Toczko Z, Fedorowicz Z, Dziki A, Danek A, Nawrocki G, Sopyło R, Markiewicz W, Kędzierawski P, Wydmański J, Polish Colorectal Study Group.

2016-02-15295 citations

10.1093/annonc/mdw062

Neoadjuvant chemoradiation for fixed cT3 or cT4 rectal cancer: Results of a Polish II multicentre phase III study.

Krzysztof Bujko, on behalf of the Polish Colorectal Study Group

Journal of Clinical Oncology2016-02-0110 citations

10.1200/jco.2016.34.4_suppl.489

Interventions

RADIATIONShort course of radiotherapy

5 x 5 Gy and afer one week interval consolidating chemotherapy of 3 courses of FOLFOX4

RADIATIONRadiochemotherapy

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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

No

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

Design outcomes

Primary

Measure	Time frame
The rate of patients with R0 resection	Surrogate endpoint available immediatly after surgery

Secondary

Measure	Time frame
Progression-free long-term survival	5 years
The rate of local failures	5 years
The rate of distant metastases	5 years
Overall long-term survival	5 years
The rate of postoperative complications	30 days
The rate of late toxicity according to the RTOG/EORTC scale	5 years
The rate of complete pathological response	Surrogate endpoint available immediatly after surgery
The rate of early toxicity of neoadjuvant treatment according to the NCI CTCAE (version 3.0)	3 months

Countries

Poland

Contacts

Primary ContactWojciech Michalski, M. S.

W.Michalski@coi.waw.pl+48226433909

Outcome results

None listed