Crossover clinical study comparing the pharmacokinetics of etoposide (75 mg) administered as 25-mg capsules three times a day versus once a day.

Some investigators have postulated that a constant low blood level might be the ideal mode of treatment while others have seen no reason to divide up the daily dose. To our knowledge this study is the first to include crossover of subjects to eradicate individual differences. Our aim was to compare the pharmacokinetic effects of administering etoposide three times a day vs. once a day as 25 mg capsules. Two groups of four patients each received 75 mg/day oral etoposide for 2 days either as 75 mg once daily or as 25 mg three times daily for 2 days. On days 8 and 9, the treatments were switched between groups. On the one-dose schedule, C-peak (peak plasma concentration) was greater than 2 mug/ml in live patients and greater than 3 mug/ml in three patients, while in none of the patients on the three-dose schedule did the peak exceed 2 mug/ml. No significant difference was found in terms of C-mean (calculated by dividing the area under the curve by the observed time) between the two treatments. Variability of blood concentrations of etoposide over a 24 h period was high on the one-dose schedule (median 95%, range 54-148%) but it was lower on the three-dose schedule (median 39%, range 28%-55%). No significant differences were found between the two different dosing schedules in terms of the median duration of etoposide blood levels above 0.5 mug/ml and above 1.0 mug/ml. These results suggest that detailed clinical toxicity and efficacy data are needed to ciarify the possible benefits of the fractionated administration of oral etoposide

Combined effects of epirubicin and tamoxifen on the cell cycle phases in estrogen-receptor-negative Ehrlich ascites tumor cells

Laboratory and clinical data suggest some interactions between cytotoxic agents and tamoxifen. The mechanisms of these interactions differ in estrogen-receptor-negative cell lines. The ability of tamoxifen to modify the effects of epirubicin on the cell-cycle phases of estrogen-receptor-negative Ehrlich's carcinoma ascitic cells (EATC) was studied in mice. The results showed that combination of tamoxifen with epirubicin decreased the thymidine labelling index more effectively than did either drug alone. Adding tamoxifen to epirubicin treatment induced both an early S-phase and G2-M-phase arrest and a later G0-G1-phase arrest in EATC. An increase of SO cells in the quiescent fraction could play a role in these changes, and some of these quiescent cells may not be viable, causing them to die later. In conclusion, the data suggest that continuous exposure to tamoxifen might modify the effects of epirubicin via cell-cycle perturbations

Prognostic significance of hemoglobin concentration in nasopharyngeal carcinoma: Does treatment-induced anemia have negative effect?

Purpose: To assess the value of hemoglobin concentration (HC) in predicting treatment outcomes in nasopharyngeal carcinoma (NPC) patients treated with chemotherapy (CT) and radiotherapy (RT). Patients and Methods: Ninety-eight NPC patients treated with three courses of platinum-based neoadjuvant CT (NCT) and conventional RT were grouped as having normal HC (greater than or equal to12.0 g/dl in females and greater than or equal to13 g/dl in males), having mild anemia (MA) (13.0 g/dl>Hbgreater than or equal to11 g/dl in males, 12.0 g/dl>Hbgreater than or equal to11 g/dl in females) and having severe anemia (SA) (Hb <11 g/dl). Massive decrease in HC (MDHC) was defined as greater than or equal to1.5 g/dl decline with NCT Along with other known risk factors (sex, age, histopathology, T stage, N stage, bilateral neck involvement, cranial nerve involvement and total RT time), the prognostic value of SA and MDHC were evaluated by Cox-regression. Results: SA increased from 7 to 33% with NCT (p<0.0001). Patients with SA had lower 5-year locoregional control (LRC) (49 vs. 73%, p=0.03), disease-free survival (DFS) (42 vs. 68%, p = 0. 01) and overall survival (OS) (43 vs. 69%, p = 0.01) rates than patients with normal HC or MA. The presence of MDHC worsened 5-year LRC (p=0.002), DFS (p=0.001) and OS (p=0.02) rates. In multivariate analyses, MDHC and SA had pronounced effect on LRC and survival, respectively. Conclusion: MDHC and SA adversely affect treatment outcome in NPC patients treated with CT and RT This may favour concomitant scheduling of RT and CT over neoadjuvant setting. Correction of HC before RT can improve the efficacy of RT and should be further evaluated

Effects of tibolone and hormone therapy (estradiol and medroxyprogesterone acetate) on the late toxic effects of radiotherapy in cervical cancer survivors: a prospective, double-blind, randomized, placebo-controlled trial

Purpose: The primary objective of this study was to investigate the efficacy of tibolone and estrogen therapies to prevent the late toxic effects of radiotherapy in the vagina in cervical cancer survivors who received radiotherapy. A secondary objective included how these therapies affected sexual life. Material and Methods: In the placebo arm, the patients received a placebo. In the tibolone arm, the patients received tibolone at a dosage of 2.5 mg daily. In the estrogen arm, patients received 0.625 mg estradiol (E2) and five mg medroxyprogesterone acetate (IVEPA) daily. The patients were assessed with the LENT-SOMA (Late Effects Normal Tissues-Subjective Objective Management and Analytic) scoring system, vaginal impression, female sexual function index (FSFI), and routine gynecological examination. Results: The LENT SOMA total score was significantly higher in the baseline measurement in all arms of the study (p<0.001). The vaginal length significantly increased in the tibolone arm (7.17 +/- 0.98 vs. 7.69 +/- 0.91;p<0.001) and E2/MPA arm (7.29 +/- 1.37 vs. 7.80 +/- 1.29; p = 0.005). The changes in FSFI total score significantly improved in the tibolone arm (16.06 +/- 6.92 vs. 22.19 +/- 6.14 vs. 26.02 +/- 12.35;p = 0.042). Conclusions: The evidence suggested that short-term tibolone or E2/MPA use appeared to reduce the late toxic effects of radiotherapy and increase the vaginal measurements, while tibolone improved sexual function especially, in cervical cancer survivors

Profile of the colorectal (CRC) cancer (Ca) patients (PTS) in Turkey: A cross-sectional disease registry study-A Turkish Oncology Group trial

WOS: 000208847100392