Combined modality therapy of rectal cancer: decreased acute toxicity with the preoperative approach.

Minsky, Bruce D.; Cohen, Alfred M.; Kemeny, Nancy E.; Enker, Warren E.; Kelsen, David P.; Reichman, Bonnie; Saltz, Leonard B.; Sigurdson, Elin R.; Frankel, Joanne

doi:10.1200/jco.1992.10.8.1218

Cited by 188 publications

(67 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Using the pCRT approach, the rate of local recurrence at 5-year ranges from 6 to 8%, 1,2 and the rate of complete pathological response ranges from 4 to 44% of cases, as reported in single institution series trials, 3,4 in phase II studies [5][6][7] and in randomized trials. 2,8 For patients with good pathologic response to pCRT, the oncological outcome has been reported to be better for 'responders' than for 'nonresponders'.…”

Section: Introductionmentioning

confidence: 95%

Tumor response is predicted by patient genetic profile in rectal cancer patients treated with neo-adjuvant chemo-radiotherapy

et al. 2010

View full text Add to dashboard Cite

The aim of the study was the identification of a pharmacogenetic profile predictive of the tumor regression grade (TRG), considered as tumor response parameter, after neo-adjuvant treatment in rectal cancer patients. A total of 238 rectal cancer patients treated in a neo-adjuvant setting by a fluoropyrimidines-based chemo-radiotherapy (RT) were genotyped for 25 genetic polymorphisms in 16 genes relevant for treatment-associated pathways. Two polymorphisms were associated with TRG in a multivariate analysis: hOGG1-1245C4G, which can affect radiosensitivity and MTHFR-677C4T, which is involved in fluoropyrimidines action. Patients bearing at least one variant allele had a lower chance to get TRGp2 (OR ¼ 0.46 95% CI 0.23-0.90, P ¼ 0.024; and OR ¼ 0.48 95% CI 0.24-0.96, P ¼ 0.034; respectively). An association trend was observed for ABCB1-3435C4T, which is responsible for the multi-drug resistance (odds ratio (OR) ¼ 1.96, 95% confidence interval (CI) 0.98-3.95, P ¼ 0.057). Exploratory classification and regression tree (CART) analysis highlighted high-order gene-gene and gene-environment interactions and a genetic signature associated with differential response, with hOGG1-1245C4G as the most predictive factor. Other significant variables were: ABCB1-3435C4T, MTHFR-677C4T, ERCC1-8092C4A, ABCC2-1249G4A, XRCC1-28152G4A, XRCC3-4541A4G and patients gender. On the basis of CART results, patients were categorized into three groups according to tumor response probability: intermediate and high profiles had a higher probability to get TRGp2 as compared with low profiles (OR ¼ 4.12 95% CI 1. Po0.001 and OR ¼ 12.44, Po0.0001, respectively). This study evidences a major role of hOGG1-1245C4G and MTHFR-677C4T polymorphisms in the tumor response of rectal cancer patients treated with chemo-RT in neo-adjuvant setting, and shows the relevance of gene-gene and gene-environment interactions for complex phenotypes as tumor response.

show abstract

Section: Introductionmentioning

confidence: 95%

Tumor response is predicted by patient genetic profile in rectal cancer patients treated with neo-adjuvant chemo-radiotherapy

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Radiotherapy or chemoradiation has been widely used to improve patient outcomes in locally advanced rectal cancer (LARC), 5-FUbased chemoradiation is an effective treatment, shown by many phase II studies (Chen et al, 1994;Kaminsky-Forrett et al, 1998;Janjan et al, 1999;Crane et al, 2003). Preoperative chemoradiation increases the resection rate (Reerink et al, 2003) and preoperative radiation or chemoradiotherapy decrease local recurrence and reduce small bowel complications compared with postoperative therapy (Minsky et al, 1992;Frykholm et al, 1993, Sauer et al, 2004. R0 resection rates of 60 -85% have reported with 5-FUbased preoperative chemoradiation for LARC (Videtic et al, 1998;Küchenmeister et al, 2000;Rödel et al, 2000).…”

mentioning

confidence: 99%

Concurrent chemoradiation with capecitabine and weekly irinotecan as preoperative treatment for rectal cancer: results from a phase I/II study

et al. 2006

View full text Add to dashboard Cite

The aim of this study was to investigate the efficacy and safety of chemoradiation using capecitabine and irinotecan as neoadjuvant therapy for patients with rectal cancer. Conventional radiation was given at daily fractions of 1.8 Gy on 5 days a week for a total dose of 55.8 (50.4 þ 5.4) Gy. Concurrently, irinotecan 40 mg m À2 once weekly and capecitabine continuously at dose levels of 500, 650, 750 and 825 mg m À2 twice daily were administered. Surgery was performed 4 -6 weeks following completion of chemoradiation. A total of 28 patients (3 UICC II, 25 UICC III) were enrolled and all received treatment. Dose-limiting toxicity was diarrhoea grade IV and hand -foot syndrome at the 825 mg m À2 dose level. The maximum tolerated dose of capecitabine was 750 mg m À2 . Diarrhoea was the most common toxicity: grade III in nine patients. Two patients died, one due to pneumonia and one due to sudden cardiac death. A complete response and only microfocal residual tumour disease was achieved in four and three patients (27%). In all, 25 of 28 patients undergoing surgery, 24 (96%) had R0 resection. Preoperative chemoradiation based on continuous daily capecitabine and weekly irinotecan appears to tolerated and effective in patients with rectal cancer.

show abstract

“…Results expressed as percentages of patients who were evaluable at each dosage level are shown above each bar (Minsky et al, 1992a) need to monitor the results of treatment and respond appropriately. The need for more effective liaison between different clinical disciplines is illustrated by the observation that preoperative radiation therapy or combined modality therapy in patients with rectal cancer who undergo surgery may be associated with a more favourable outcome (reduced toxicity and better preservation of sphincter function) than post-operative therapy (Minsky et al, 1992ci;Rouanet et al, 1995;Hyams et al] 1997;Maghfoor et al, 1997).…”

Section: Designing Therapies To Enhance Patient-centred Outcomesmentioning

confidence: 99%

“…The need for more effective liaison between different clinical disciplines is illustrated by the observation that preoperative radiation therapy or combined modality therapy in patients with rectal cancer who undergo surgery may be associated with a more favourable outcome (reduced toxicity and better preservation of sphincter function) than post-operative therapy (Minsky et al, 1992ci;Rouanet et al, 1995;Hyams et al] 1997;Maghfoor et al, 1997). An example of how patient-centred end-points such as reduced incidence of acute side-effects and the avoidance of permanent colostomy might be used to improve the overall effectiveness of treatment is shown by the following data from the Memorial Sloan-Kettering Cancer Center (Minsky et al, 1992a). Post-operative radiation plus systemic chemotherapy is the most effective adjuvant therapy after surgery for transmural and/or node-positive resectable rectal cancer (Gastrointestinal Tumor Study Group, 1985;Douglass et al, 1986;Krook et al, 1992).…”

Section: Designing Therapies To Enhance Patient-centred Outcomesmentioning

confidence: 99%

Multidisciplinary case teams: an approach to the future management of advanced colorectal cancer

Minsky

1998

Br J Cancer

View full text Add to dashboard Cite

Summary The effective management of advanced colorectal cancer has traditionally been viewed in terms of treatment outcome measures such as efficacy (survival, objective response and palliation) and safety. Although these outcomes are of paramount importance and are essential for the evaluation of the effectiveness and tolerability of treatment, they do not take account of the global effect of therapy on patients, society and healthcare systems. Furthermore, they may not reveal important differences between treatments of equivalent antitumour efficacy that might influence the overall effectiveness in terms of acceptability of therapy. To achieve this, a broader, patient-centred evaluation of advanced cancer treatment is required that acknowledges the views, experience and perspectives of all involved in the treatment process. To this end, the International Working Group in Colorectal Cancer, a multidisciplinary group that encompasses expertise from a range of relevant fields and disciplines, has advocated a multidisciplinary approach to the treatment of advanced colorectal cancer that is likely to deliver the best possible overall care.

show abstract

Combined modality therapy of rectal cancer: decreased acute toxicity with the preoperative approach.

Abstract: Given the high incidence of grade 3 to 4 toxicity also reported in the postoperative combined modality adjuvant randomized trials, future adjuvant trials should explore the preoperative approach.

Cited by 188 publications

References 0 publications

Tumor response is predicted by patient genetic profile in rectal cancer patients treated with neo-adjuvant chemo-radiotherapy

Tumor response is predicted by patient genetic profile in rectal cancer patients treated with neo-adjuvant chemo-radiotherapy

Concurrent chemoradiation with capecitabine and weekly irinotecan as preoperative treatment for rectal cancer: results from a phase I/II study

Multidisciplinary case teams: an approach to the future management of advanced colorectal cancer

Contact Info

Product

Resources

About