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

Intraperitoneal cisplatin - mitoxantrone in ovarian cancer patients with minimal residual disease

A phase II trial was conducted to further explore the potential of salvage intraperitoneal (IP) cisplatin-based therapy in patients with residual ovarian cancer. Twenty-five patients were treated with a regimen of cisplatin (75 mg/m(2)) and mitoxantrone (15 mg/m(2)) delivered IP every three weeks for a maximum of six cycles. Ten patients achieved a pathologically complete response (pCR) and six were clinically stable without evidence of disease. After a median follow-up of 18 months, the median progression-free survival (PFS) was 16 months (95% confidence interval - CI - 3-29%). The actuarial PFS at 24 months was 36% (95% CI 13-59). Overall eight out of 25 patients (32%) had an IP relapse and thus were considered as local treatment failures, The major toxic side effects were nausea, vomiting abdominal pain and renal toxicity. Future trials exploring IP delivery nf these drugs should attempt rn optimite drug dose and schedule and subset analysis of clinical studies should help in identifying patients who are particularly sensitive to this therapeutic approach

The efficacy and safety of venlafaxine in the prophylaxis of migraine

Objective.-To evaluate the efficacy and safety of venlafaxine in the prophylaxis of migraine

Clinical significance of serum protease activated receptor1 levels in patients with lung cancer

OBJECTIVE: Protease-Activated receptors (PAR) are G protein coupled receptors and they regulate many biological processes, including coagulation and cell survival and they might be good markers in some types of malignant tumors, providing useful information in diagnosis and prognosis. The objective of this study was to determine the clinical significance of the serum levels of PAR1 in lung cancer patients. PATIENTS AND METHODS: Eighty patients with lung cancer were enrolled into this study. Serum PAR1 levels were determined by the solid- phase sandwich ELISA method. Median age was 58.5-years old, range 36 to 80 years. RESULTS: The majority of the patients had NSCLC (85%) and stage IV disease (56%). The baseline serum PAR1 concentrations of the lung cancer patients were significantly higher than control group (median values 26.45 ng/mL v 0.07 ng/mL, p 0.05). Moreover, it failed to show any prognostic value on the survival of the lung cancer patients. CONCLUSIONS: The serum levels of PAR1 might have a diagnostic value in lung cancer patients. However, its predictive and prognostic values were not determined

Serum matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 in patients with malignant melanoma

Degradation of basement membranes and extracellular matrix is an essential step in cancer invasion and metastasis. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play key roles in this step. The present study was conducted to investigate the levels of MMP-3 and TIMP-1 in serum of patients with malignant melanoma and the relationship to tumor progression and known prognostic parameters. Seventy patients with cutaneous malignant melanoma were investigated. Serum samples were obtained on first admission before any adjuvant and metastatic treatment was given or follow-up of patients. Serum TIMP-I and MMP-3 levels were determined by the solid-phase sandwich ELISA (Oncogene Science Inc.) method. The elevation of serum MMP-3 and TIMP-1 levels between the patients with malignant melanoma and healthy controls were not significantly different (p > 0.05). The serum levels of MMP-3 were significantly different in males and females (p = 0.001) and serum TIMP levels were influenced by age (p = 0.047). Except for the ulceration status of the tumor, serum levels of MMP-3 and TIMP-1 were not related to the known prognostic factors such as tumor histology, localization, stage of the disease, Breslow thickness, Clark invasion, mitosis, TIL, and regression of tumor (p > 0.05). In patients with ulceration positive, the serum levels of MMP-3 were higher (p = 0.04) and TIMP-I were lower (p = 0.008) than those in patients without ulceration. No significant relationship was found between serum levels of MMP-3 and TIMP-1. In conclusion, these results suggest that neither of the serum levels of MMP-3 and TIMP-I could be a good indicator of invasion and metastasis nor can be recommended as a tumor marker in the management of melanoma patients owing to lack of sensitivity and specificity. However, much research still continues in this field and exciting new knowledge will ultimately emerge

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

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