Improving Adjuvant Therapy for Rectal Cancer by Combining Protracted-Infusion Fluorouracil with Radiation Therapy after Curative Surgery

O’Connell, Michael J.; Martenson, James A.; Wieand, Harry S.; Krook, James E.; Macdonald, John S.; Haller, Daniel G.; Mayer, Robert J.; Gunderson, Leonard L.; Rich, Tyvin A.

doi:10.1056/nejm199408253310803

Cited by 1,058 publications

(409 citation statements)

References 18 publications

Supporting

Mentioning

355

Contrasting

Unclassified

Order By: Relevance

“…However, combined with radiotherapy, a continuous regimen seemed to be a hypothetically more attractive schedule, mimicking the postoperative adjuvant setting, in which the optimal approach to the treatment of resected T3 -4/N0 -2 rectal cancer includes radiotherapy combined with concurrent, continuous infusion 5FU (O'Connell et al, 1994). Furthermore, in nonrandomised trials of preoperative radiotherapy combined with continuous infusion 5FU, a pathologic complete response rate of 16 -29%, low toxicity profile and no obvious increase in surgical morbidity have been reported (Rich et al, 1995;Ngan et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Combined postoperative radiotherapy and chemotherapy reduces the rate of local recurrence and prolongs survival in patients with Dukes B2 and C rectal cancer (Thomas and Lindblad, 1988;Krook et al, 1991;O'Connell et al, 1994). As a result, adjuvant chemoradiation has been recommended as standard therapy for Dukes B2 and C rectal cancer (NIH Consensus Conference, 1990).…”

mentioning

confidence: 99%

“…However, preoperative radiotherapy in conventional fractionation schedules, given concurrently with continuous infusion 5-fluorouracil (5FU), has been widely adopted as the preferred preoperative regimen, given the acceptable toxicity profile and efficacy when this regimen is given in the postoperative setting (O'Connell et al, 1994).…”

mentioning

confidence: 99%

See 2 more Smart Citations

A phase I trial of preoperative radiotherapy and capecitabine for locally advanced, potentially resectable rectal cancer

et al. 2004

View full text Add to dashboard Cite

The purpose of the study was to determine the maximum-tolerated dose (MTD) of oral capecitabine, combined with concurrent, standard preoperative pelvic radiotherapy, when given twice daily, from Monday to Friday throughout the course of radiotherapy, for locally advanced potentially resectable rectal cancer. Maximum-tolerated dose was defined as the total (given in two equally divided doses) oral dose of capecitabine that caused treatment-related grade 3 or 4 toxicity in one-third or more of the patients treated. Radiotherapy involved 50.4 Gy given in 28 fractions in 5 weeks and 3 days. Eligible patients had a newly diagnosed clinical stage T3 -4 N0 -2 M0 rectal adenocarcinoma located within 12 cm of the anal verge suitable for curative resection. Surgery was performed 4 -6 weeks from completion of preoperative chemoradiotherapy. In all, 28 patients were enrolled in the study at predefined dose levels: 850 mg m À2 day À1 (n ¼ 3), 1000 mg m À2 day À1 (n ¼ 6), 1250 mg m À2 day À1 (n ¼ 3), 1650 mg m À2 day À1 (n ¼ 3), 1800 mg m À2 day À1 (n ¼ 8) and 2000 mg m À2 day À1 (n ¼ 5). The mean age was 62.3 years (range: 33 -80 years). Five patients were female and 23 male. The median distance of tumour from the anal verge was 6 cm (range: 1 -11 cm). Endorectal ultrasound was performed in 93% of patients. A total of 26 patients (93%) had T3 disease and two patients had resectable T4 disease. Dose-limiting toxicity (DLT) developed in one patient at dose level 1000 mg m À2 day À1 (RTOG grade 3 cystitis). Two of the five patients at dose level 2000 mg m À2 day À1 had a total of three DLT (grade 3 perineal skin reaction, grade 3 diarrhoea and grade 3 dehydration). Dose escalation of capecitabine was ceased at 2000 mg m À2 day À1 after reaching MTD. None of the eight patients at dose level 1800 mg m À2 day À1 developed DLT. All except one patient underwent surgery. A total of 15 patients had the clinical T stage reduced by at least one stage in pathologic specimens. Five patients (19%) achieved a pathologic complete response. We conclude that the MTD of capecitabine was reached at a dose level of 2000 mg m À2 day À1 , given as 1000 mg m À2 twice daily, from Monday to Friday throughout the course of preoperative pelvic irradiation of 50.4 Gy. For patients with resectable rectal cancer receiving concurrent, full dose radiotherapy, the recommended dose of capecitabine for further study is 1800 mg m À2 day À1 when given in this schedule.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

A phase I trial of preoperative radiotherapy and capecitabine for locally advanced, potentially resectable rectal cancer

et al. 2004

View full text Add to dashboard Cite

show abstract

“…Clinical trials have demonstrated clearly that chemoradiation treatment of various human cancer types (e.g., advanced cervical, esophageal, colorectal) is associated with significantly increased patient survival compared to treatment with radiation or drug alone [35][36][37]. These studies have also demonstrated a clear advantage for concurrent chemoradiation treatments as opposed to sequential treatments (i.e., drug given before or after radiation) [38].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of cell survival, DNA double strand breaks, and DNA synthesis during concurrent camptothecin and X‐radiation treatments

Mazaheri

Payant

et al. 2001

Intl Journal of Cancer

View full text Add to dashboard Cite

SUMMARY We evaluated cell survival, DNA double strand breaks (dsbs), and DNA synthesis following camptothecin (CPT) alone or concurrent CPT and X-radiation treatments in exponential-phase cultures of a radioresistant human melanoma cell line. Cell survival was measured by a clonogenic assay. DNA dsbs were measured by pulsed-field gel electrophoresis. DNA synthesis was measured by incorporation of 3 H-thymidine. We found that (i) concurrent CPT and X-radiation interacted additively, unlike previous results with plateau-phase cultures of these cells, which showed synergistic interaction; (ii) there were strong negative correlations (correlation coefficients of at least 0.82) between clonogenic surviving fractions and DNA dsbs following CPT alone or concurrent CPT and radiation treatments; and (iii) concurrent CPT and radiation (10 Gy) treatment did not completely inhibit DNA synthesis, even though addition of radiation to CPT did further decrease DNA synthesis (relative to CPT alone) at CPT concentrations below 20 µM. Our results suggest that during concurrent CPT and radiation treatment residual DNA dsb levels were good indicators of cell killing and that the absence of complete inhibition of DNA synthesis could at least in part explain the additive interaction between CPT and radiation.

show abstract

“…Standard preoperative CRT combines radiation with a dose of 46-50.4 Gy with 5-fluorouracil (5-FU) chemotherapy given either as bolus injections with Leucovorin, prolonged continuous infusion (likely better than bolus) or oral capecitabine [39][40][41]. Combined CRT is followed by TME surgery 6-8 weeks later.…”

Section: Patient Selection and Neoadjuvant Therapymentioning

confidence: 99%

Laparoscopic extraperitoneal rectal cancer surgery: the clinical practice guidelines of the European Association for Endoscopic Surgery (EAES)

et al. 2011

View full text Add to dashboard Cite

Background The laparoscopic approach is increasingly applied in colorectal surgery. Although laparoscopic surgery in colon cancer has been proved to be safe and feasible with equivalent long-term oncological outcome compared to open surgery, safety and long-term oncological outcome of laparoscopic surgery for rectal cancer remain controversial. Laparoscopic rectal cancer surgery might be efficacious, but indications and limitations are not clearly defined. Therefore, the European Association for Endoscopic Surgery (EAES) has developed this clinical practice guideline. Methods An international expert panel was invited to appraise the current literature and to develop evidence-based recommendations. The expert panel constituted for a consensus development conference in May 2010. Thereafter, the recommendations were presented at the annual congress of the EAES in Geneva in June 2010 in a plenary session. A second consensus process (Delphi process) of the recommendations with the explanatory text was necessary due to the changes after the consensus conference. Results Laparoscopic surgery for extraperitoneal (midand low-) rectal cancer is feasible and widely accepted. The laparoscopic approach must offer the same quality of surgical specimen as in open surgery. Short-term outcomes such as bowel function, surgical-site infections, pain and hospital stay are slightly improved with the laparoscopic approach. Laparoscopic resection of rectal cancer is not

show abstract

Improving Adjuvant Therapy for Rectal Cancer by Combining Protracted-Infusion Fluorouracil with Radiation Therapy after Curative Surgery

Abstract: A protracted infusion of fluorouracil during pelvic irradiation improved the effect of combined-treatment postoperative adjuvant therapy in patients with high-risk rectal cancer. Semustine plus fluorouracil was not more effective than a higher dose of systemic fluorouracil given alone.

Cited by 1,058 publications

References 18 publications

A phase I trial of preoperative radiotherapy and capecitabine for locally advanced, potentially resectable rectal cancer

A phase I trial of preoperative radiotherapy and capecitabine for locally advanced, potentially resectable rectal cancer

Evaluation of cell survival, DNA double strand breaks, and DNA synthesis during concurrent camptothecin and X‐radiation treatments

Laparoscopic extraperitoneal rectal cancer surgery: the clinical practice guidelines of the European Association for Endoscopic Surgery (EAES)

Contact Info

Product

Resources

About