A phase I study of weekly oxaliplatin (OXA), 5-fluorouracil (5-FU) continuous infusion and preoperative radiotherapy in locally advanced rectal cancer

Aschele, C.; Friso, Maria Luisa; Pucciarelli, Salvatore; Babris, G.; Martella, Bruno; Dalt, Gianfranco Da; Urso, E.; Neri, Daniele; Lora, O.; Monfardini, S.

doi:10.1016/s0959-8049(01)80745-0

Cited by 8 publications

(10 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Phase I/II trials are examining the use of new chemotherapeutic agents in combination with pelvic radiation therapy, most commonly in the preoperative setting. Selected agents include UFT [89][90][91] , Tomudex [92], oxaliplatin [90,91,[93][94][95][96][97][98][99][100][101][102][103], [104][105][106][107][108], Gefitinib (Iressa) [109], and capecitibine [110][111][112] with pelvic radiation therapy. Clinical trials of combined modality therapy in combination with novel targeted agents such as bevacizumab (Avastin) and C225 are under development [113].…”

Section: Novel Combined Modality Regimensmentioning

confidence: 99%

Combined modality therapy of resectable rectal cancer: current approaches

Minsky

2004

Tech Coloproctol

View full text Add to dashboard Cite

There are two conventional treatments for clinically resectable rectal cancer. First is surgery and, if the tumor is in stage T3 or N1-2, this is followed by postoperative combined modality therapy. The second is preoperative combined modality therapy followed by surgery and postoperative combined modality therapy if the tumor is classified at ultrasound as uT3-4 or N+. A number of new chemotherapeutic agents have been developed for the treatment of patients with colorectal cancer. Ongoing phase I and II trials are examining the use of these new chemotherapeutic agents in combination with pelvic radiation therapy, most commonly in the preoperative setting; early results suggest that the complete response rates are higher. Based on results from phase I and II trials, the standard regimen for patients who receive combined modality therapy is continuous infusion 5-fluorouracil (5-FU) and pelvic radiation. Regimens using CPT-11 or oxaliplatin-based combined modality therapy plus either continuous infusion 5-FU or capecitibine are under active development.

show abstract

Section: Novel Combined Modality Regimensmentioning

confidence: 99%

Combined modality therapy of resectable rectal cancer: current approaches

Minsky

2004

Tech Coloproctol

View full text Add to dashboard Cite

show abstract

“…A phase I‐II study of oxaliplatin and 5‐FU in the pre‐operative treatment of locally advanced rectal cancer has recently been conducted in Italy [27]. A weekly treatment schedule was developed for the study, with the objective of reducing acute toxicity through dose fractionation, and achieving greater overall dose intensity.…”

Section: Oxaliplatinmentioning

confidence: 99%

“…Interim results were reported in May 2002, at which point 39 patients, including 23 males and 16 females had entered the trial, with a median age of 60 years [28]. All the patients had locally advanced rectal cancer and 30 patients had nodal involvement.…”

Section: Oxaliplatinmentioning

confidence: 99%

“… Oxaliplatin, 5FU and radiotherapy in locally advanced rectal cancer: response rates in a phase I/II study [28]. …”

Section: Oxaliplatinmentioning

confidence: 99%

“…Assays are still needed to quantify precisely the level of DNA damage associated with radiation and oxaliplatin used separately and in combination, but the preclinical studies to date strongly confirm that oxaliplatin is a potent radiosensitiser. A phase I-II study of oxaliplatin and 5-FU in the preoperative treatment of locally advanced rectal cancer has recently been conducted in Italy [27]. A weekly treatment schedule was developed for the study, with the objective of reducing acute toxicity through dose fractionation, and achieving greater overall dose intensity.…”

Section: Oxaliplatinmentioning

confidence: 99%

See 2 more Smart Citations

Radiochemotherapy in rectal cancer: the role of oxaliplatin

et al. 2003

Self Cite

View full text Add to dashboard Cite

Radiation therapy is well established in the treatment of early and locally advanced rectal cancer, where it has been used in both the pre-operative and postoperative settings. Pre-operatively, radiation therapy has been shown in a series of studies culminating in the Dutch total mesorectal excision (TME) study to significantly reduce the rate of local recurrence at 2 years. However, the overall rate of survival was not improved in this study because radiotherapy failed to reduce the incidence of distant metastases. Chemotherapy, however, may reduce distant metastatic spread, as well as increasing the rate of R0 resectability and sphincter-saving surgery when used in combination with radiotherapy in the neoadjuvant setting. Oxaliplatin is a prime candidate for radiochemotherapy in rectal cancer because it frequently has large and rapid cytoreductive effects in colorectal malignancies and has been shown in vitro and preclinical models to be radiosensitizing. In an Italian phase I/II study, weekly oxaliplatin combined with standard infusional 5-FU and pre-operative radiotherapy has shown low toxicity and promising antitumour activity. These encouraging results are now being followed up in a more extensive trials programme. A randomized trial comparing this regimen with standard infusional FUra and radiotherapy (STAR, Studio nazonaleTerapia neoAdiuvante Retto [National Study on Neoadjuvant Treatment of Rectal cancer]) is being launched in Italy. A new phase II study, CORE (Capecitabine, Oxaliplatin, Radiotherapy and Excision), is now in development in Europe and will use a similar weekly treatment regimen with an oral fluropyrimidine in place of infusional FUra, and a number of further oxaliplatin-based radiochemotherapy studies in rectal cancer are planned or in progress. In summary, radiochemotherapy appears to have the potential to significantly improve clinical outcomes in rectal cancer, and oxaliplatin-based treatment is proving central to its ongoing development.

show abstract

Adjuvant therapy for rectal cancer – the transatlantic view

Minsky

2003

Colorectal Disease

View full text Add to dashboard Cite

In North America there are two conventional treatments for clinically resectable rectal cancer. First is surgery and, if the tumour is T3 and/or N1-2, this is followed by postoperative combined modality therapy. The second, for patients with ultrasound T3 or clinical T4 disease, is pre-operative combined modality therapy followed by surgery and postoperative chemotherapy. Pre-operative therapy (most commonly combined modality therapy) has gained acceptance as a standard adjuvant therapy. The potential advantages of this approach compared with postoperative therapy include less acute toxicity and enhanced sphincter preservation. Recently completed randomized trials in the US and Germany will provide a definitive answer to this theory. In contrast to the combined modality approach to pre-operative therapy a number of European centres advocate an intensive short course of radiation (5 Gy x 5 followed one week later by surgery). The only randomized trial which has revealed a significant advantage in survival is the Swedish Rectal Cancer Trial. The Dutch CKVO 95-04 TME trial did not confirm a survival advantage and two metanalyses report conflicting results. Due to selection bias, it is not possible accurately to compare the local recurrence and survival results of intensive short course radiation with conventional pre-operative combined modality therapy. The intensive short course radiation approach is not used in North America due to its higher toxicity and lack of sphincter preservation. In the Dutch trial the 5-year local recurrence was 12% with TME and was significantly decreased to 6% with pre-operative radiation. The 5-year local recurrence rate in the 324 patients with stage III disease who underwent a TME alone with negative margins was 20%. Therefore, despite TME surgery, radiation therapy is still a necessary component in the adjuvant management of rectal cancer.

show abstract

A phase I study of weekly oxaliplatin (OXA), 5-fluorouracil (5-FU) continuous infusion and preoperative radiotherapy in locally advanced rectal cancer

Cited by 8 publications

References 18 publications

Combined modality therapy of resectable rectal cancer: current approaches

Combined modality therapy of resectable rectal cancer: current approaches

Radiochemotherapy in rectal cancer: the role of oxaliplatin

Adjuvant therapy for rectal cancer – the transatlantic view

Contact Info

Product

Resources

About