Results of a phase III, double-blind, placebo-controlled trial of megestrol acetate modulation of P-glycoprotein-mediated drug resistance in the first-line management of small-cell lung carcinoma

Antiemetic activity of megestrol acetate in patients receiving chemotherapy

“…All adverse events were mild and transient. Although thromboembolic disease was reported in several studies [19,21,22], there were no thromboembolic diseases reported in this study because low-dose and short-term administration of megestrol acetate were used. The rate of side effects was similar in the two regimens, except for increased appetite, which appeared to be more pronounced in the megestrol acetate regimen, and this side effect has been widely recognized.…”

“…Those patients who received megestrol acetate had significantly less nausea (p= 0.0002) and vomiting (p=0.02). However, the rates of vomiting and nausea were not different between the MA arm and the placebo arm in another trial [19].Thus, megestrol acetate seemed to fare well even when compared to an accepted antiemetic drug. This is the first study to aim directly at the antiemetic efficacy of megestrol acetate.…”

Expression of breast cancer resistance protein is associated with a poor clinical outcome in patients with small-cell lung cancer

“…Some studies have shown a relationship between expression of Pgp or MRP1 and response or survival [19][20][21][22][23], however, their clinical usefulness as therapeutic targets is still obscure. In fact, two randomized phase III studies that incorporated modulators of Pgp and one phase II study of VX-710, an inhibitor of both Pgp and MRP1, failed to show any survival benefit in SCLC patients [24][25][26].…”

MDR1 gene polymorphisms and P-glycoprotein expression in respiratory diseases

“…In cancer therapy, many attempts have been made to reverse MDR mechanisms. However, in a randomized double-blind trial in 130 SCLC patients no positive effects were seen with the P-gp modulator megestrol acetate in addition to chemotherapeutic drugs, suggesting that levels of P-gp expression in lung tumors were not relevant or that modulation of P-gp activity was not complete in this treatment 51 . Although immunosuppressive agents such as cyclosporine A and tacrolimus (both calcineurin antagonists) are P-gp substrates, no relation was found of MDR1 G2677T and C3435T genotypes with tacrolimus blood levels in 83 lung transplant patients treated with tacrolimus 52 .…”