Determination of the optimal dose of 5-fluorouracil when combined with low dose d,l-leucovorin and irradiation in rectal cancer: Results of three consecutive phase II studies

Bosset, J.-F.; Pavy, JJ; Hamers, Han; Horiot, Jean-Claude; Fabri, M; Rougier, Philippe; Eschwège, F.; Schraub, S

doi:10.1016/0959-8049(93)90012-5

Cited by 72 publications

(19 citation statements)

References 13 publications

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“…acute toxicity observed in our trial was high and highly comparable to other studies (13,17,31). However, the higher haematologic toxicity observed in our study and in that of Bosset et al was certainly caused by the intravenous bolus administration of 5-FU in contrast to the continuous infusion of 5-FU reported by Sauer et al (32).…”

Section: Discussionsupporting

confidence: 87%

Chemoradiotherapy with 5-fluorouracil/leucovorin, surgery and adjuvant chemotherapy for locally advanced rectal cancer

et al. 2010

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Abstract. the aim of this study was to demonstrate a pathologic complete response (pcr) rate of at least 10% with an acceptable toxicity achieved by preoperative chemoradiotherapy with 5-fluorouracil (5-FU)/leucovorin in patients with locally advanced rectal cancer. Patients were treated by radiotherapy targeting 50 Gy and 5-FU/leucovorin intravenously during the 1st, 4th and 7th week after start of radiotherapy followed by surgery and adjuvant chemotherapy. In 71 evaluable patients, the pcr rate was 14.1% (95% cI, 6.0-22.2); the local relapse rate, 6.1%; the 5-year disease-free survival, 54% and the overall 5-year survival, 68%. the most severe adverse events were neutropenia (17%), diarrhoea (17%), infection (8%) and fatal cardiovascular function (1%). this therapy yielded a high rate of pcr, a low rate of local relapse and a long disease-free and overall survival. to increase its feasibility, radiation dose reduction to 45 gy and administration of only two preoperative cycles of chemotherapy is recommended. IntroductionIn the 1990s adjuvant 5-fluorouracil (5-FU)-based chemotherapy combined with radiotherapy in patients with stage II and III rectal cancer after surgical resection was established as the new standard of care decreasing the rate of local recurrence and improving patient survival (1,2). A significant change in the treatment of rectal cancer occurred with the introduction of total mesorectal excision (tMe) resulting in decreased local recurrences and improved survival (3). In 1995, when this trial started, preoperative therapy was applied to downstage tumors in order to increase sphincter-sparing surgery in distal rectal tumors and to decrease the overall toxicity.We conducted a single centre phase II trial in order to investigate the feasibility and outcome of 5-FU-based preoperative chemotherapy combined with long-term irradiation followed by surgical treatment including tMe, followed by postoperative 5-FU-based chemotherapy. The results, after a median follow-up of approximately three years (38.9 months; range 2.8-108.2 months), are presented and discussed within the context of the results published in the literature. Patients and methodsPatients were enrolled between november 1995 and november 2004. eligibility criteria included histopathologically confirmed adenocarcinoma of the rectum [according to the 1987 International Union Against Cancer (UICC) staging system] within 15 cm of the anal verge. the clinical tnM stage was assessed by clinical examination, rigid proctoscopy, endorectal ultrasonography, computed tomography scanning and nuclear magnetic resonance of the abdomen and pelvis. Patients with t3, t4 and with distal t2 (<4 cm from the anal verge) rectal cancers, respectively, were included irrespective of their nodal status. Patients with a single hepatic or lung metastasis were eligible. Patients were required to have a leukocyte level >3.0x109 /l and a thrombocyte level >100x10 9 /l, normal liver function with bilirubin values <2 mg/ dl and normal renal function with creatinine value...

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Section: Discussionsupporting

confidence: 87%

Chemoradiotherapy with 5-fluorouracil/leucovorin, surgery and adjuvant chemotherapy for locally advanced rectal cancer

et al. 2010

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“…In the case described, a complete pathological response was achieved (stage pCR). This has been found to occur in 5-15% of patients undergoing 5-fluorouracil based chemoradiotherapy, 2 and appears to indicate a good prognosis. 4 In this case, although the situation at one time appeared rather hopeless, radical emergency surgical treatment was justified.…”

Section: Discussionmentioning

confidence: 99%

“…Chemoradiotherapy was commenced 20 weeks following the initial presentation, consisting of 45 Gy of pelvic radiation in 25 daily fractions over 5 weeks using a three field technique in the prone position plus leucovorin 20 mg/m 2 and 5-fluorouracil 350 mg/m 2 intravenously on days 1-5 and 29-33. 2 Treatment was well tolerated with no dose-limiting toxicity. A subsequent MRI scan confirmed tumour shrinkage and suggested that a curative resection was now feasible.…”

Section: Department Of Surgery York Hospital York Ukmentioning

confidence: 92%

Necrotising fasciitis secondary to locally advanced rectal cancer

Woodcock¹,

Sebag‐Montefiore²,

Mannion³

et al. 2006

Ann R Coll Surg Engl

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“…Sequential dose-finding studies from France [13] and the U.S. [14] confirmed the optimum dose of 5-fluorouracil (5-FU) and both low-dose folinic acid and high-dose folinic acid in combination with RT. Others integrated a prolonged venous infusion of 5-FU [15], which, in later studies, appeared to have higher efficacy [16].…”

Section: Introductionmentioning

confidence: 92%

Locally Advanced Rectal Cancer: What Is the Evidence for Induction Chemoradiation?

Glynne‐Jones

Harrison

2007

The Oncologist

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Disclosure: R.G.-J. has received honoraria for lectures and advisory boards and has been supported in attending international meetings by Merck, Pfizer, Sanofi-Aventis, and Roche. He has also received unrestricted grants for research from Merck, SanofiAventis, and Roche. M.H. has received honoraria for lectures and advisory boards and has been supported in attending international meetings by Merck, Astra-Zeneca, Pfizer, Sanofi-Aventis, and Roche. LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Interpret the results of the relevant randomized trials of neoadjuvant induction chemoradiation from Europe and the U.S.2. Explain why induction chemoradiation is preferred over postoperative adjuvant chemoradiation.3. Discuss the rationale for using neoadjuvant induction chemoradiation in rectal cancer.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME Conclusions. CRT in the European randomized trials of rectal cancer improves tumor downstaging, pathological complete response, and local control over radiotherapy alone, but does not translate into a benefit in terms of longer DFS or OS, or a higher chance of sphincter preservation. Metastatic disease remains a significant problem, which provides a strong rationale for the integration of a second cytotoxic drug, or biologically targeted agents. The ABSTRACT

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Determination of the optimal dose of 5-fluorouracil when combined with low dose d,l-leucovorin and irradiation in rectal cancer: Results of three consecutive phase II studies

Cited by 72 publications

References 13 publications

Chemoradiotherapy with 5-fluorouracil/leucovorin, surgery and adjuvant chemotherapy for locally advanced rectal cancer

Chemoradiotherapy with 5-fluorouracil/leucovorin, surgery and adjuvant chemotherapy for locally advanced rectal cancer

Necrotising fasciitis secondary to locally advanced rectal cancer

Locally Advanced Rectal Cancer: What Is the Evidence for Induction Chemoradiation?

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