Role of Gemcitabine in the Treatment of Ovarian Cancer

Abstract

The US FDA has recently approved the combination of carboplatin and gemcitabine as a second-line therapy for recurrent platinum-sensitive ovarian cancer. This article briefly reviews the pharmacokinetics and mechanism of action of gemcitabine and its synergistic effect with platinum. An overview of the literature on the role of gemcitabine in the treatment of epithelial ovarian cancer is also presented.

Gemcitabine Eliminates Double Minute Chromosomes from Human Ovarian Cancer Cells

“…Gene amplification is a form of genomic instability that is frequently seen in cancers, and it can manifest cytogenetically as homogeneously staining regions (HSRs) or double minute chromosomes (DMs) [1], [2], [3], [4]. DMs are autonomously replicating, acentric, and atelometric circular DNA ranging from hundreds of kilobases to a few megabases in size [5], [6], [7], [8], [9], [10].…”

“…Upon the approval of the use of GEM in the treatment of ovarian cancers in Europe, USA, and other countries in recent years, GEM is becoming a promising new drug in the treatment of ovarian cancers. Recently GEM has been shown to be effective in the treatment of ovarian cancers especially in the platinum resistant subclass, either used alone or in combination with other drugs [1], [40], [44], [45], [46].…”

CD34 + progenitor-derived NK cell and gemcitabine combination therapy increases killing of ovarian cancer cells in NOD/SCID/IL2Rg null mice

“…Mice were treated with gemcitabine twice weekly for 2 weeks followed by 1-week rest, for two cycles, which is similar to treatment of ovarian cancer patients. 18 Tumor growth dose-dependently decreased in mice receiving gemcitabine ( Figure 5a-b ). Since no dosage-related toxicity was observed, we continued with the highest dosage.…”

“…Our gemcitabine dosage (40 mg/kg twice weekly) and administration schedule is comparable to other studies in mice 13,[30][31][32][33][34][35][36][37][38] and lower than in patients (human equivalent dose in mg/kg = animal dose in mg/kg/ (Km human/Km mouse) = 40/(37/3) = 3.24 mg/kg, 39 corresponding to 120 mg/m 2 twice weekly (dose in mg/m 2 = dose in mg * Km = 3.24 * 37), 39 which is ~4-fold lower than the recommended dosage of 1000 mg/m 2 once weekly in patients). 18 However, since gemcitabine is administered i.v. in patients, the concentration in the peritoneal cavity of patients will likely be lower, decreasing the difference between the mouse and human dosage.…”