Randomized trial of cyclophosphamide, methotrexate, and fluorouracil chemotherapy added to tamoxifen as adjuvant therapy in postmenopausal women with node-positive estrogen and/or progesterone receptor-positive breast cancer: a report of the National Cancer Institute of Canada Clinical Trials Group. Breast Cancer Site Group.

Pritchard, Kathleen I.; Paterson, Alexander; Fine, Shai; Paul, Nancy; Zee, Benny; Shepherd, Lois E.; Abu-Zahra, Hakam; Ragaz, Joseph; Knowling, Margaret A.; Levine, Mark; Verma, S.; Perrault, D. J.; Walde, P. L. D.; Bramwell, Vivien; Poljicak, M; Boyd, Norman F.; Warr, David; Norris, B.; Bowman, D. M. J. S.; Armitage, George; Weizel, H. A. E.; Buckman, Robert

doi:10.1200/jco.1997.15.6.2302

Cited by 87 publications

(23 citation statements)

References 26 publications

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“…Non-anthracycline-containing regimens were thought to be preferable because of the fear of cardiac toxicity in older patients, but regimens such as CMF showed no significant advantage over tamoxifen in different trials involving older women [80,81]. The IBCSG [81] examined the toxicity encountered in the elderly subgroup of patients treated with three cycles of classic CMF planned at full doses and found a significant relationship between older age and increased incidence of grade 3 toxicity from adjuvant chemotherapy, with no significant difference in survival between the treatment groups.…”

Section: Chemotherapymentioning

confidence: 99%

Treatment of breast cancer in older women

et al. 2008

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Section: Chemotherapymentioning

confidence: 99%

Treatment of breast cancer in older women

et al. 2008

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“…MCF-7A25F3 cells (5x10 6 cells/mouse) were subcutaneously inoculated into the right flank of the mice. Mice bearing a tumor of ~200-400 mm 3 in volume were selected and were randomly allocated to control and treatment groups of 5 mice each. The mice received 6-week oral administration of capecitabine (days 1-14, every 3 weeks) at two thirds MTD and/or letrozole, at 0.1 mg/kg/day.…”

Section: Methodsmentioning

confidence: 99%

“…A suspension of MCF-7 cells (5x10 6 cells/mouse) was subcutaneously inoculated into the right flank of the BALB/c-nu/nu mice which had been subcutaneously implanted with slow-release estrogen pellets (0.25 mg/pellet 17β-estradiol; Innovative Research of America, Sarasota, FL) the day before tumor cell inoculation. Several weeks after tumor inoculation, mice bearing a tumor of ~200-400 mm 3 in volume were selected and were randomly allocated to control and treatment groups. Each group consisted of 8 mice.…”

Section: Methodsmentioning

confidence: 99%

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Antitumor activity of chemoendocrine therapy in premenopausal and postmenopausal models with human breast cancer xenografts

Kataoka¹,

Yamaguchi

Moriya³

et al. 2011

Oncol Rep

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Abstract.We examined the efficacy of chemoendocrine therapy using capecitabine as a chemotherapeutic agent in premenopausal and postmenopausal models with estrogen receptor (ER)-positive human breast cancer xenografts. Tamoxifen and letrozole were used as endocrine therapeutic agents for premenopausal and postmenopausal models, respectively. The antitumor activity of capecitabine in combination was significantly superior to either monotherapy treatment in both premenopausal (p<0.01) and postmenopausal (p<0.05) models. No increase in toxicity in terms of body weight loss was observed during treatment in either of the xenograft models. In the premenopausal model, the level of thymidine phosphorylase (TP), a key enzyme generating 5-FU from capecitabine, was upregulated (p<0.05) in tumors by tamoxifen but not by letrozole treatment in the postmenopausal model. The combination of 5'-deoxy-5-fluorouridine (5'-DFUR; an intermediate of capecitabine) with 4-hydroxytamoxifen (4-OHT; an active form of tamoxifen) or letrozole was also evaluated in vitro by using estrogen-responsive element (ERE) reporter gene assays aimed to model premenopausal and postmenopausal breast cancer. Both combinations decreased the number of estrogenresponding cells in a concentration-dependent manner and further analysis by isobolograms revealed a synergistic effect of the combination of 5'-DFUR with 4-OHT, and at least an additive effect of the combination of 5'-DFUR with letrozole. These results suggest that chemoendocrine therapy using capecitabine may be a useful treatment modality for patients with hormone-receptor-positive breast cancer, regardless of the menopausal status and should be explored in clinical trials. IntroductionTwo decades ago, in vitro antagonism in cytotoxicity was reported between chemotherapeutic agents and antiestrogens in breast cancer cells (1). This observation translated to the clinic as results with chemoendocrine therapies in patients have been disappointing (2,3). However, not all reports of addition of chemotherapies, such as CMF [a chemotherapy regimen consisting of cyclophosphamide, methotrexate and 5-fluorouracil (5-FU)], to endocrine therapies showed negative results. For example, clinical results from NSABP B-20 trial (4) and the International Breast Cancer Study Group (IBCSG) trial VII (5) indicated that the addition of CMF to tamoxifen yielded superior five-year disease-free survival rate. Therefore, it is likely that some chemotherapeutic agents may not be antagonistic to antiestrogens.Capecitabine is an oral 5-FU derivative widely used for breast cancers which generates the active substance 5-FU in tumors by a three-step cascade of enzymes located in the liver and tumors. The final step is the conversion of 5'-DFUR, an intermediate metabolite, to 5-FU by TP, which is highly expressed in tumors. Therefore, a higher level of 5-FU would be expected in tumor tissues which have higher expression levels of TP, when treated with capecitabine. Indeed, it has been reported that the antitumor activity of capecit...

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“…Several individual trials and large meta-analysis have contributed to the building-up of the present state of art [5][6][7][8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, oestrogen receptor-positive breast cancer patients. Very late results of the ‘gruppo di ricerca per la chemio-ormonoterapia adiuvante (GROCTA)’ 01-Trial in early breast cancer

Boccardo

Guglielmini

Parodi

et al. 2011

Breast Cancer Res Treat

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Abstract: The addition of CMF to TAM adds no benefit and considerable toxicity in this group of women.

Cited by 87 publications

References 26 publications

Treatment of breast cancer in older women

Treatment of breast cancer in older women

Antitumor activity of chemoendocrine therapy in premenopausal and postmenopausal models with human breast cancer xenografts

Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, oestrogen receptor-positive breast cancer patients. Very late results of the ‘gruppo di ricerca per la chemio-ormonoterapia adiuvante (GROCTA)’ 01-Trial in early breast cancer

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