Cyclophosphamide, Adriamycin, 5-Fluorouracil and High-dose Toremifene for Patients with Advanced/Recurrent Breast Cancer

Abstract

Background: Multi-combination chemotherapy consisting of anthracyclines has been effective but has not invariably prolonged the survival period in advanced/recurrent breast cancer. The possibility has been discussed that chemoendocrine therapy combined with endocrine agents is more effective. Methods: In order to evaluate the toxicity and efficacy of a new endocrine therapy for advanced/recurrent breastcancer, we ran a pilot study during the period from July 1994to July 1996. Results: Twenty-two patients with advanced/recurrent breast cancer were treated with chemoendocrine therapy consisting of cyclophosphamide (100 mg/body) p.o. daily for 14 days, with adriamycin (40 mg/m 2) i.v. and 5-fluorouracil (500 mg/body) i.v, on day 1 (repeated every 3 weeks for 9 weeks) (CAF therapy), and high-dose toremifene (120 mg/body) p.o. daily. Of 20 evaluable patients, two showed complete response (10 %), eight partial response (40%), six no change (30%) and four progressive disease (20%). The overall response ratewas 50%, and the median duration of response was 69.5 days (28-133+ days). The major toxicities were drug-induced alopecia, gastrointestinal toxicity andhematological toxicity, butthesewereclinically well tolerated. No serious cardiac, liver or renal symptom was seen. Conclusions: Based on these results, we consider the addition of high-dose toremifene to the CAF therapy to be useful in the treatment of advanced and recurrent breast cancer.

Investigation Binding Patterns of Human Carboxylesterase I (hCES I) with Broad Substrates by MD Simulations

“…Heroin is also used as analgesics, and is hydrolyzed 6-acetylmorphine by hCES1 [79]. Capecitabine clinically used as an oral drug treatment in gastrointestinal and breast cancers [80,81] and it can be converted to 5'-deoxy-5-fluorocytidine in the liver and further hydrolyzed to 5-fluorouracil which is an active chemotherapy agent [82]. CPT-11 is an anticancer prodrug, and hCES1 is essential to the activation of it [75].…”

Recurrent Male Breast Cancer Accompanied by Carcinomatous Pleuritis That Responded to Combination Therapy with High-Dose Toremifene and Docetaxel

“…These facts indicate that high-dose TOR may act as a chemosensitizer to overcome multiple drug resistance and diminish side effects. Following the idea, several reports have demonstrated the efficacy of high-dose TOR as an enhancer for treatment beyond second-line chemotherapy in TAM-refractory recurrent female breast cancers [14,15].…”

2′-Deoxy-N4-[2-(4-nitrophenyl)ethoxycarbonyl]-5-azacytidine: A novel inhibitor of DNA methyltransferase that requires activation by human carboxylesterase 1

“…Capecitabine can be converted to 5'-deoxy-5-fluorocytidine by carboxylesterase in the liver and then is further metabolized to 5-fluorouracil the active chemotherapy agent [31]. This drug is currently clinically used as an oral form of 5-fluorouracil in gastrointestinal and breast cancers [33,34].…”