A prospective randomized trial of fluorouracil versus fluorouracil plus cisplatin in the treatment of metastatic colorectal cancer: a Hoosier Oncology Group trial.

Loehrer, Patrick J.; Turner, S; Kubilis, Paul; Hui, Shuang; Correa, J; Ansari, Rafat; Stephens, Deborah M.; Woodburn, Robert; Meyer, S

doi:10.1200/jco.1988.6.4.642

Cited by 66 publications

(25 citation statements)

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“…However, the effect of cisplatin on colorectal cancer is weak. Loehrer et al (1988) and Grem et al (1993) reported rates of response of colorectal cancer to cisplatin-based chemotherapy of 22 and 19%, respectively. On the other hand, for oxaliplatin-based chemotherapy, de Gramont et al (2000) reported that the response rate was 50%.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, its spectrum of activity and mechanisms of action or resistance differ from those of cisplatin (Raymond et al, 2002;Fuertes et al, 2003;Wang and Lippard, 2005). Oxaliplatin is used against colorectal cancers as a key drug in FOLFOX regimens, and its objective response rate for colorectal cancer is superior to that of cisplatin (Loehrer et al, 1988;Grem et al, 1993;de Gramont et al, 2000;Andre et al, 2004). However, the molecular mechanism(s) underlying the clinical results and that reason that oxaliplatin has such a potent anticolorectal cancer effect compared with cisplatin are unclear.…”

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confidence: 99%

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Significance of Organic Cation Transporter 3 (SLC22A3) Expression for the Cytotoxic Effect of Oxaliplatin in Colorectal Cancer

Yokoo

Masuda²,

Yonezawa

et al. 2008

Drug Metab Dispos

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ABSTRACT:The effect of oxaliplatin against colorectal cancer is superior to that of cisplatin, but the molecular mechanism(s) involved is not clear. We found previously that oxaliplatin, but not cisplatin, was transported by human (h) and rat organic cation transporter 3 (OCT3)/SLC22A3. In the present study, we examined whether hOCT3 was significantly involved in the oxaliplatin-induced cytotoxicity and accumulation of platinum in colorectal cancer. The level of hOCT3 mRNA in the colon was 9.7-fold higher in cancerous than in normal tissues in six Japanese patients (P ‫؍‬ 0.0247). In human colorectal cancer-derived cell lines, the mRNA of hOCT3 was highly expressed compared with that of other organic cation transporters. The release of lactate dehydrogenase (LDH) and accumulation of platinum with oxaliplatin treatment were increased in SW480 cells transfected with hOCT3 cDNA compared with empty vector-transfected cells. T84 and SW837 cells, with high levels of hOCT3, released more LDH and accumulated more platinum after oxaliplatin treatment than low hOCT3-expressing cells such as SW480, HCT116, HT29, and Lovo. However, the amount of platinum accumulated after cisplatin treatment did not differ among these six cell lines. The levels of hOCT3 expression in colon and rectum were also higher in cancerous than in normal tissues in Caucasian patients as determined by dot blotting. In conclusion, the hOCT3-mediated uptake of oxaliplatin into the cancers was suggested to be important for its cytotoxicity, and hOCT3 expression may be a marker for cancer chemotherapy including oxaliplatin.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Significance of Organic Cation Transporter 3 (SLC22A3) Expression for the Cytotoxic Effect of Oxaliplatin in Colorectal Cancer

Yokoo

Masuda²,

Yonezawa

et al. 2008

Drug Metab Dispos

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“…Several treatment modalities have been studied consisting of cytostatics alone (Loehrer et al, 1988) or of cytostatics in combination with other agents (Wadler et al, 1989) or with radiotherapy (Boulis Wassif, 1982). Although the use of adjuvants of treatments found effective for advanced disease has been disappointing, recent results appear to confirm the beneficial effects of cytostatics if administered in the immediate postoperative period (Mayer, 1990).…”

Section: Discussionmentioning

confidence: 99%

Intraperitoneal cytostatics impair healing of experimental intestinal anastomoses

Zuidewijn

Hendriks²,

Wobbes³

et al. 1991

Br J Cancer

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Summary We investigated the effect of two doses of cytostatics, administered intraperitoneally during 5 consecutive days, on the healing of ileal and colonic anastomoses constructed on the third day. The cytostatics regimen consisted of a combination of 5-fluorouracil, bleomycin and cisplatin at 10, 2 and 0.35 mg kg-'d', respectively, or at twice higher doses. The lower dose was similar to that given intravenously in previous experiments. Rats were sacrificed 3 or 7 days after operation. No effects of cytostatics were observed after 3 days, neither on anastomotic bursting pressure nor on hydroxyproline concentration (jLg/mg dry weight) or content (ug cm-'). Profound effects were seen at 7 days. In the high dose group, bursting pressures in both anastomoses were greatly reduced with respect to the control group. Concurrently, collagen synthesis was severely impaired, as indicated by sustained decreased hydroxyproline concentrations and content. The lower dose of cytostatics showed essentially similar effects on hydroxyproline parameters, but affected anastomotic strength less dramatically. The data indicate that, while intraperitoneal chemotherapy may show less detrimental systemic toxicity and thus allow higher doses, its application as an adjunct to gastrointestinal surgery may be limited because of its severe effects on anastomotic repair.

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“…Neither study found differences in response and overall survival; one of these trials reported the median duration of remission was superior for uorouracil alone (p ¾ 0.05) (104).…”

Section: Fluorouracil In Combination With Cisplatinmentioning

confidence: 95%

A Systematic Overview of Chemotherapy Effects in Colorectal Cancer

Ragnhammar¹

2001

Acta Oncologica

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A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scienti c literature are described separately (Acta Oncol 2001; 40: 155 -65). This synthesis of the literature on adjuvant and palliative therapy with cytostatics for colorectal cancer is based on 208 scienti c articles, including eight meta-analyses and 162 randomised studies. These studies involve approximately 126 800 patients. The conclusions reached can be summarized into the following points:The bene t of postoperative adjuvant chemotherapy with uorouracil and levamisole in patients with colon cancer stage Dukes' C was demonstrated more than ten years ago in two phase III trials. There was a reduction of recurrence from 56% to 39% and reduction of death from 51% to 40% after more than ve years of follow-up. Although this combination has been widely accepted as standard adjuvant treatments for stage Dukes' C colon cancer, there is still debate on whether adjuvant treatment with uorouracil alone would be equally ef cacious. Several phase III trials with postoperative adjuvant chemotherapy with uorouracil and leucovorin in patients with colon cancer stage Dukes' C have demonstrated a similar statistically signi cant improvement in disease-free and overall survival in comparison with a control arm. Six months of treatment with uorouracil and leucovorin is as ef cient as twelve months of uorouracil and levamisole. This treatment is, thus, recommended for routine use. No convincing bene t from adjuvant chemotherapy is proven in colon cancer stage Dukes' B although some randomised trials have shown the same relative survival gain as seen in stage Dukes' C. There is less knowledge on survival bene ts from adjuvant chemotherapy for Dukes' stage B and C rectal cancer. In small randomised trials, postoperative radiochemotherapy has, however, improved survival to the same extent as chemotherapy in colon cancer Dukes' stage C. A meta-analysis of nine randomised trials revealed a small but statistically signi cant bene t in ve-year survival and a reduction in the risk of death for the patients receiving immediate postoperative portal vein infusion compared with controls. At present, however, the use of portal vein infusion or intraperitoneal therapy outside of a research trial cannot be recommended in the light of the limited effects. This conclusion is further supported by similarly limited effects in two recently reported very large European multicentre trials. In advanced colorectal cancer, chemotherapy may prolong survival, decrease tumour-related symptoms, improve general well-being or maintain it at a high level for a longer time period compared with best supportive care. These effects have been seen using systemic chemotherapy and using regional chemotherapy in patients with metastases limited to the liver. Subjective responses and quality of life improvements are seen more frequently than objective tumour remissions. Altho...

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A prospective randomized trial of fluorouracil versus fluorouracil plus cisplatin in the treatment of metastatic colorectal cancer: a Hoosier Oncology Group trial.

Cited by 66 publications

References 5 publications

Significance of Organic Cation Transporter 3 (SLC22A3) Expression for the Cytotoxic Effect of Oxaliplatin in Colorectal Cancer

Significance of Organic Cation Transporter 3 (SLC22A3) Expression for the Cytotoxic Effect of Oxaliplatin in Colorectal Cancer

Intraperitoneal cytostatics impair healing of experimental intestinal anastomoses

A Systematic Overview of Chemotherapy Effects in Colorectal Cancer

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