1.
SLC22 transporter family proteins as targets for cytostatic uptake into tumor cells.
Gupta, S, Burckhardt, G, Hagos, Y
Biological chemistry. 2011;(1-2):117-24
Abstract
The response to chemotherapy by tumor cells depends on the concentration of cytostatics accumulated inside the cells. The accumulation of anticancer drugs in tumor cells is mainly dependent on functional expression of efflux and influx transporters and to a minor extent on passive diffusion through the membrane. Efflux transporters of the ABC family are partially responsible for the chemoresistance of cancer cells by secreting these cytostatics. Over the past decades, the role of ABC transporters in the chemoresistance of various malignant tumors has been very well documented. By contrast, very little is known about the impact on tumor therapy of influx transporters belonging to the solute carrier transporters (SLC family). In this review, we focus on the interaction of SLC22 transporters with cytostatics, the expression of these transporters in tumor cells as well as their impact on the chemosensitivity of cancer cells.
2.
A phase II trial of UFT and leucovorin in women 65 years and older with advanced breast cancer.
Gupta, S, Mauer, AM, Ryan, CW, Taber, DA, Samuels, BL, Fleming, GF, ,
American journal of clinical oncology. 2005;(1):65-9
Abstract
The incidence of breast cancer increases with age. This trial evaluated the efficacy and safety of oral UFT (ftorafur plus uracil) plus leucovorin in elderly patients with advanced breast cancer. Eligibility criteria included age > or =65 years, locally advanced or metastatic breast cancer, < or =1 prior chemotherapy regimens in the setting of metastatic disease, performance status 0-2, and adequate end-organ function. UFT at 300 mg/m2 per day as 2 divided doses and 30 mg leucovorin with each dose were administered orally daily for 21 days, followed by a 7-day rest period. Ten patients were accrued. Six patients received treatment in their first relapse and 3 in their second. One patient was chemotherapy-naive. The dose-limiting toxicity was diarrhea with grade 3 or 4 diarrhea occurring more often in the oldest patients (1 of 6 patients between 65 and 69 vs. 3 of 4 patients > or =70 years old). Protocol treatment was discontinued in 2 patients (ages 78 and 83) secondary to severe gastrointestinal toxicity. One patient achieved a partial response. Although UFT/leucovorin had efficacy in 1 patient, toxicity in the patients over 70 years of age was increased. Careful evaluation of anticancer drug toxicity in very elderly patients is important as our population ages.