A phase II study of continuous infusion 5-fluorouracil and leucovorin with weekly cisplatin in metastatic colorectal carcinoma

Grem, Jean L.; McAtee, Nanette; Balis, Frank M.; Murphy, Robert F.; Venzon, David; Kramer, Barnett S.; Goldspiel, Barry R.; Begley, Martin; Allegra, Carmen J.

doi:10.1002/1097-0142(19930801)72:3<663::aid-cncr2820720307>3.0.co;2-v

Cited by 29 publications

(12 citation statements)

References 12 publications

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“…Oxaliplatin has a much more potent anticolorectal cancer effect than cisplatin (Grem et al, 1993;de Gramont et al, 2000). However, the molecular mechanism(s) that cause the difference in the effect has not been made clear.…”

Section: Discussionmentioning

confidence: 99%

“…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%

Section: Discussionmentioning

confidence: 99%

mentioning

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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“…It is metabolized to its active form 5-fluoruracil (5-FU) by the enzyme thymidine phosphorylase, which exists in higher concentrations in tumor tissue and liver than in normal tissues. 5-FU has been associated with megaloblastic changes, likely secondary to DNA-directed toxicity (Grem et al, 1993). There has been some studies showing the effect of MCV increase on prognosis in patients with metastatic breast cancer treated with Capecitabine (Arslan et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Haematologic Parameters in Metastatic Colorectal Cancer Patients Treated with Capecitabine Combination Therapy

İnanç

Duran²,

Karaca³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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MCV showed significant increase in chemotherapy response groups (PR and SD). In addition, a significant decrease was observed for platelet count in chemotherapy response groups. While NLR decrease was seen in only a PR group, PCT decrease was observed in all three groups. PCT and PLT values were higher in patients receiving Bevacizumab. Conclusions: PLT, PCT, MPV, and NLR values were decreased due to Capecitabinebased chemotherapy, however MCV was increased. PCT and PLT values were higher in patients who received Bevacizumab than those who did not. MCV, PLT, and NLR can be considered as important factors in predicting response to colorectal carcinoma treatment.

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“…By contrast, the efficiency of cisplatin is generally low in colorectal cancer, with <20% clinical responses when used alone or in combination with 5-fluorouracil or etoposide (3,4). Oxaliplatin is a third-generation platinum coordination complex of the 1,2-diaminocyclohexane families, having been developed after cisplatin and carboplatin (5,6).…”

Section: Introductionmentioning

confidence: 99%

Role of p21waf1/cip1 in effects of oxaliplatin in colorectal cancer cells

Hata

Yamamoto

Ngan

et al. 2005

Molecular Cancer Therapeutics

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Clinical studies have shown that oxaliplatin, a novel platinum derivative, is a potent chemotherapeutic agent for colorectal cancer when combined with 5-fluorouracil and leucovorin. Although the toxic activity is based on covalent adducts between platinum and DNA, its actual biological behavior is mostly unknown. In an effort to explore the mechanism of tumor susceptibility to oxaliplatin, we examined the cytotoxic effects of oxaliplatin in colorectal cancer cell lines in reference to p53 gene status. Although p53 gene status did not clearly predict sensitivity to oxaliplatin, p53 wild-type cells including HCT116 were sensitive but HCT116 p53 À/À were found to be resistant to oxaliplatin. Oxaliplatin caused strong p21 waf1/cip1 induction and G 0 -G 1 arrest in p53 wild-type cells, whereas cisplatin did not induce G 0 -G 1 arrest. Assays using p53 wild but p21 waf1/cip1 null HCT116 cells revealed that oxaliplatin did not show G 0 -G 1 arrest and reduced growth-inhibitory effects, suggesting that p21 waf1/cip1 may be a key element in oxaliplatin-treated p53 wild-type cells. Although HCT116 is DNA mismatch repair -deficient, a mismatch repair -proficient HCT116+ch3 cell line displayed similar responses with regard to p21 waf1/cip1 -mediated growth inhibition and G 0 -G 1 arrest. In p53 mutant cells, on the other hand, oxaliplatin caused an abrupt transition from G 1 to S phase and eventually resulted in G 2 -M arrest. This abrupt entry into S phase was associated with loss of the p21 waf1/cip1 protein via proteasome-mediated degradation. These findings suggest that p21 waf1/cip1 plays a role in oxaliplatin-mediated cell cycle and growth control in p53-dependent and -independent pathways. [Mol Cancer Ther 2005;4(10):1585 -94]

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A phase II study of continuous infusion 5-fluorouracil and leucovorin with weekly cisplatin in metastatic colorectal carcinoma

Cited by 29 publications

References 12 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

Haematologic Parameters in Metastatic Colorectal Cancer Patients Treated with Capecitabine Combination Therapy

Role of p21waf1/cip1 in effects of oxaliplatin in colorectal cancer cells

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