Preoperative chemotherapy and pelvic radiation for tethered or fixed rectal cancer: A phase II dose escalation study

Chan, Alexander; Wong, Alfred; Langevin, James M.; Jenken, Daryl A.; Heine, J.; Buie, Donald; Johnson, Douglas

doi:10.1016/s0360-3016(00)00692-1

Cited by 84 publications

(66 citation statements)

References 37 publications

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“…In our study, over 40% of patients had T4 tumours representing a group of patients with truly locally advanced disease. This may account for the low pathological complete response rate seen in our study compared with 10 -30% achieved in other studies (Janjan et al, 1999;Bosset et al, 2000;Chan et al, 2000;Grann et al, 2001;Onaitis et al, 2001;Valentini et al, 2001). Two studies included only patients with clinically staged T4 tumours (Videtic et al, 1998;Rodel et al, 2000).…”

Section: Discussioncontrasting

confidence: 47%

“…Many recent studies included T3 tumours staged by endoscopic ultrasound which are often less bulky than clinically staged T3 tumours. Very few patients with T4 tumours were recruited (o5% of total enrolled) in these studies (Janjan et al, 1999;Bosset et al, 2000;Chan et al, 2000;Grann et al, 2001;Onaitis et al, 2001;Valentini et al, 2001). In our study, over 40% of patients had T4 tumours representing a group of patients with truly locally advanced disease.…”

Section: Discussionmentioning

confidence: 99%

“…Preoperative MMC, infused 5-FU/leucovorin and radiotherapy have also been shown to be an effective treatment for tethered/fixed rectal cancers (Chan et al, 2000). The objectives of this study were to evaluate the feasibility and benefits of delivering neoadjuvant chemotherapy prior to synchronous chemoradiation and surgery in patients with newly diagnosed locally advanced rectal cancer.…”

mentioning

confidence: 99%

“…In patients with locally advanced, primarily irresectable cancer (i.e. a cancer where a complete gross surgical clearance is deemed unlikely to be achieved), preoperative CRT has been used to cause tumour regression to such an extent that the cancer can be removed radically with adequate clearance in the resection margin (Videtic et al, 1998;Chan et al, 2000;Rodel et al, 2000).…”

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confidence: 99%

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Neoadjuvant systemic fluorouracil and mitomycin C prior to synchronous chemoradiation is an effective strategy in locally advanced rectal cancer

et al. 2003

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This study was designed to evaluate the benefits of neoadjuvant chemotherapy prior to chemoradiation and surgery in patients with locally advanced rectal cancer. Patients with previously untreated primary rectal cancer, reviewed in a multidisciplinary meeting and considered to have locally advanced disease on the basis of physical examination and imaging (MRI+CT n ¼ 30, CT alone n ¼ 6), were recruited. Patients received protracted venous infusion 5-FU (300 mg m À2 day À1 for 12 weeks) with mitomycin C (MMC) (7 mg m À2 i.v. bolus every 6 weeks). Starting on week 13, 5-FU was reduced to 200 mg m À2 day À1 and concomitant pelvic radiotherapy 45 Gy in 25 fractions was commenced followed by 5.4 -9 Gy boost to tumour bed. Surgery was planned 6 weeks after chemoradiation. Postoperatively, patients received 12 weeks of MMC and 5-FU at the same preoperative doses. Between January 99 and August 01, 36 eligible patients were recruited. Median age was 63 years (range ¼ 40 -85). Following neoadjuvant chemotherapy, radiological tumour response was 27.8% (one CR and nine PRs) and no patient had progressive disease. In addition, 65% of patients had a symptomatic response including improvement in diarrhoea/constipation (59%), reduced rectal bleeding (60%) and diminished pelvic pain/tenesmus (78%). Following chemoradiation, tumour regression occurred in 80.6% (six CRs and 23 PRs; 95% CI ¼ 64 -91.8%) and only one patient still had an inoperable tumour. R0 resection was achieved in 28 patients (82%). When compared with initial clinical staging, the pathological downstaging rate in T and/or N stage was 73.5% and pathological CR was found in one patient. Neoadjuvant systemic chemotherapy as a prelude to synchronous chemoradiation can be administered with negligible risk of disease progression and produces considerable symptomatic response with associated tumour regression.

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Section: Discussioncontrasting

confidence: 47%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Neoadjuvant systemic fluorouracil and mitomycin C prior to synchronous chemoradiation is an effective strategy in locally advanced rectal cancer

et al. 2003

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“…The combination seems to improve the effect of radiotherapy. This has clearly been proved in a randomized trial including 585 patients with anal cancer (13) and it may also apply to patients with fixed rectal tumours (14). It is not clear whether the improvement in combination with radiotherapy can be explained by increased radiosensitivity or is due to the cytostatic effect per se.…”

Section: Discussionmentioning

confidence: 97%

A phase II study of UFT and leucovorin in combination with mitomycin C in patients with metastatic colorectal cancer

Gyldenkerne

Glimelius²,

Frödin³

et al. 2004

Acta Oncologica

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Predictive immunohistochemical features for tumour response to chemoradiotherapy in rectal cancer

et al. 2020

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Background Reduced expression of cluster of differentiation (CD) 133 and cyclo‐oxygenase (COX) 2, and increased density of CD8+ tumour‐infiltrating lymphocytes, are associated with a favourable tumour response to preoperative chemoradiotherapy (CRT). This study aimed to evaluate these markers in relation to tumour response after preoperative CRT in two rectal cancer cohorts. Methods Patients with low rectal cancer who underwent radical resection and preoperative short‐term CRT in 2001–2007 (retrospective cohort) and long‐term CRT in 2011–2017 (prospective cohort) were analysed. Pretreatment biopsies were stained immunohistochemically using antibodies to determine CD133 and COX‐2 expression, and increased CD8+ density. Outcome measures were tumour regression grade (TRG), tumour downstaging and survival. Results For 95 patients in the retrospective cohort, the incidence of TRG 3–4 was 67 per cent when two or three immunohistochemistry (IHC) features were present, but only 20 per cent when there were fewer features (P < 0·001). The incidence of tumour downstaging was higher in patients with at least two IHC features (43 versus 22 per cent with fewer features; P = 0·029). The 49 patients in the prospective cohort had similar rates to those in the retrospective cohort (TRG 3–4: 76 per cent for two or more IHC features versus 25 per cent with fewer features, P < 0·001; tumour downstaging: 57 versus 25 per cent respectively, P = 0·022). Local recurrence‐free survival rates in patients with more or fewer IHC features were similar in the retrospective and prospective cohort (P = 0·058 and P = 0·387 respectively). Conclusion Assessment of CD133, COX‐2 and CD8 could be useful in predicting a good response to preoperative CRT in patients with lower rectal cancer undergoing neoadjuvant therapy. Further studies are needed to validate the results in larger cohorts and investigate a survival benefit.

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Preoperative chemotherapy and pelvic radiation for tethered or fixed rectal cancer: A phase II dose escalation study

Cited by 84 publications

References 37 publications

Neoadjuvant systemic fluorouracil and mitomycin C prior to synchronous chemoradiation is an effective strategy in locally advanced rectal cancer

Neoadjuvant systemic fluorouracil and mitomycin C prior to synchronous chemoradiation is an effective strategy in locally advanced rectal cancer

A phase II study of UFT and leucovorin in combination with mitomycin C in patients with metastatic colorectal cancer

Predictive immunohistochemical features for tumour response to chemoradiotherapy in rectal cancer

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