Patients With Rectal Cancer: a "Wait-and-see" Approach

Официальное название

Radical External Beam Chemoradiation in Patients With Rectal Cancer: a "Wait-and-see" Approach

Обзор

Patients with histologically proven adenocarcinoma of the rectum will receive pelvic radiotherapy to a dose of 45Gy in 25 fractions with a tumor boost to a dose of 9Gy in 5 fractions (thus total of 54Gy/30Fx to the primary tumor), combined with radio sensitizing chemotherapy. Patients will then be closely monitored, through endoscopy and imaging, for response to treatment and relapse. Salvage oncologic surgery to be offered if there is failure to achieve complete clinical response or in the event of a loco regional relapse.

Подробное описание

The combination of preoperative (chemo)radiotherapy and total mesorectal excision (TME) has been shown to reduce the risk of local recurrence in patients with resectable adenocarcinoma of the rectum. The improved local control rates come at the price of an increased risk of surgical complications, including a postoperative death rate of 2-8 percent which may reach 30 per cent at 6 months in those aged over 85 years, as well as long-term impact on anorectal, urinary and sexual function. Patients with cancers in the low rectum in close proximity to the sphincter muscles, may require a permanent stoma, which can be associated with high psychological morbidity.

Preoperative chemoradiotherapy followed by a delay to resection can produce pathological complete responses. One review of phase II and III studies identified an overall pCR rate of 13.5%, but even higher rates of pCR have been observed with doses of radiotherapy exceeding 45 Gy . Certainly patients who proceed to radical surgery after achieving a pCR with chemo radiation do have favorable long-term outcomes. But do patients whose tumor has already been sterilized by chemo radiotherapy need to proceed with radical surgery?

A number of studies have now emerged highlighting the rationale of a 'wait and see' policy for patients who achieve a complete clinical response (cCR) after chemo radiotherapy. The majority of the clinical data supporting this approach have come from Brazil. The Brazilian data suggests that observation of such patients yields survival rates similar to those of patients who undergo radical surgery with confirmation of pCR. More recent studies from the United Kingdom and the Netherlands appear to support the feasibility of this approach. To date there is no published prospectively collected data of a wait-and-see policy from a North American Centre.

Вмешательства

• Лучевая терапия Radical external beam radiotherapy
  pelvic radiotherapy to a dose of 45 Gy in 25 fractions with a tumor boost to a dose of 9 Gy in 5 fractions (thus total of 54 Gy/30 fractions to the primary tumor), combined with radio sensitizing chemotherapy.

Первичные конечные точки

• Feasibility of a "wait and see" approach [Срок оценки: One year]

Критерии участия

Критерии включения

• Pelvic MRI defined disease (at least one of the following):

• mesorectum involved or breached - includes involvement of adjacent organ (s) (T3-T4)
• involvement of muscularis propria (T2)
• extra-mural vascular invasion
• tumour deposit within the mesorectum
• one or more involved mesorectal lymph node
• Patients are considered medically fit for oncologic resection
• ECOG performance status 0 or 1
• No evidence of established metastatic disease (CT chest and abdomen)
• Absolute neutrophil count >1.5x109/L; platelets >100x109/L,
• Serum transaminase <3 x ULN;
• Adequate renal function (Cockroft Gault estimation >50 mL/min)
• Bilirubin <1.5 x ULN
• Ability to comply with oral medication
• Willingness and ability to give informed consent and comply with treatment and follow up schedule
• Age 18 or over

Критерии исключения

• Previous radiotherapy to the pelvis (including brachytherapy)
• Enlarged extramesorectal nodes
• Uncontrolled cardiorespiratory comorbidity (includes patients with inadequately controlled angina or myocardial infarction within 6 months of randomisation)
• T1N0 disease without extra-mural venous invasion
• Unequivocal evidence of metastatic disease (includes resectable metastases)
• Major impairment of bowel function without defunctioning stoma/ileostomy (baseline grade 3 diarrhoea or clinically significant faecal incontinence)
• History of another malignancy within the last 5 years except successfully treated basal cell cancer of skin or carcinoma in situ of uterine cervix.
• Known dihydropyrimidine dehydrogenase deficiency
• Known Gilberts disease (hyperbilirubinaemia)
• Taking warfarin or phenytoin or sorivudine
• Gastrointestinal disorder which would interfere with oral therapy and its bioavailability
• Pregnant, lactating, or pre-menopausal women not using adequate contraception
• Unfit to receive any study treatment or subsequent surgical resection

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Канада · 2 центра

• McGill University Health Center-Cedars Cancer Centre — Montreal
• McGill University Health Centre- Cedars Cancer Centre — Montreal

Публикации

• Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Ollier JC; EORTC Radiotherapy Group Trial 22921. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006 Sep 14;355(11):1114-23. doi: 10.1056/NEJMoa060829. PMID 16971718
• Gerard JP, Conroy T, Bonnetain F, Bouche O, Chapet O, Closon-Dejardin MT, Untereiner M, Leduc B, Francois E, Maurel J, Seitz JF, Buecher B, Mackiewicz R, Ducreux M, Bedenne L. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006 Oct 1;24(28):4620-5. doi: 10.1200/JCO.2006.06.7629. PMID 17008704
• Peeters KC, Marijnen CA, Nagtegaal ID, Kranenbarg EK, Putter H, Wiggers T, Rutten H, Pahlman L, Glimelius B, Leer JW, van de Velde CJ; Dutch Colorectal Cancer Group. The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma. Ann Surg. 2007 Nov;246(5):693-701. doi: 10.1097/01.sla.0000257358.56863.ce. PMID 17968156
• Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R; German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004 Oct 21;351(17):1731-40. doi: 10.1056/NEJMoa040694. PMID 15496622
• Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, Quirke P, Couture J, de Metz C, Myint AS, Bessell E, Griffiths G, Thompson LC, Parmar M. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009 Mar 7;373(9666):811-20. doi: 10.1016/S0140-6736(09)60484 PMID 19269519
• van Gijn W, Marijnen CA, Nagtegaal ID, Kranenbarg EM, Putter H, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van de Velde CJ; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol. 2011 Jun;12(6):575-82. doi: 10.1016/S1470-2045(11)70097-3. Ep PMID 21596621
• Borowski DW, Bradburn DM, Mills SJ, Bharathan B, Wilson RG, Ratcliffe AA, Kelly SB; Northern Region Colorectal Cancer Audit Group (NORCCAG). Volume-outcome analysis of colorectal cancer-related outcomes. Br J Surg. 2010 Sep;97(9):1416-30. doi: 10.1002/bjs.7111. PMID 20632311
• Paun BC, Cassie S, MacLean AR, Dixon E, Buie WD. Postoperative complications following surgery for rectal cancer. Ann Surg. 2010 May;251(5):807-18. doi: 10.1097/SLA.0b013e3181dae4ed. PMID 20395841

Идентификаторы

NCT: NCT03001362 · 14-407 GEN

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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