Phase I experience with emetine hydrochloride (NSC 33669) as an antitumor agent

Abstract

This report details a Phase I dose-ranging experiment of the use of emetine in patients with a variety of malignant diseases. The data show that emetine can be given intravenously a t 4-day intervals with minimal toxicity. Severe muscle weakness, the most important dose-limiting toxic effect, began a t approximately a 15 mg/kg cumulative dose level and resulted in discontinuance of therapy i n two patients. Of 5 patients who received greater than 10.4 mg/kg, 2 stabilized previously rapidly progressive disease, one had marked reduction in a purulent bloody vaginal discharge, a n d 2 who had received the highest total dose had 50% or greater reduction i n lung tumor size. T h e present data suggest a reasonable regimen t o be 1.5 mg/kg I V weekly for a minimum total dose of 15 nig/kg. Emetine is not myelosuppressive and therefore may be useful i n the patient with poor marrow reserve. Alternatively, it can be used in combination with agents of different toxicities in hope of showing additive effects without additive toxicity. METINE, AN ALKALOID OF Cephaelis ipe-

Overcoming adaptive resistance in mucoepidermoid carcinoma through inhibition of the IKK-β/IκBα/NFκB axis

“…Emetine has been widely used to treat amoebiasis since the early 1900s [59]. The earliest report describing the use of Emetine as an anti-neoplastic drug dates to 1918; however, Phase I/II clinical trials using emetine were not performed by the NCI until the mid-1970s [60–62]. Due to disparate results with Emetine, ranging from no clinical benefit to disease stabilization/tumor regression, it was not widely studied for its anti-neoplastic properties for many years.…”

Design, Synthesis, and Evaluation of pH-Dependent Hydrolyzable Emetine Analogues as Treatment for Prostate Cancer

“…7 As a protein synthesis inhibitor, its anticancer activities were investigated in several phase I-II clinical trials in a number of solid tumors between 1969 and 1974. 8-13 While clinical responses were observed in these studies, emetine was reported to have a very narrow therapeutic index, and dose dependent side effects such as muscle fatigue and cardiac toxicity were observed. These were the same side effects observed in the treatment of amoebiasis patients.…”

The alkaloid emetine as a promising agent for the induction and enhancement of drug-induced apoptosis in leukemia cells

“…Blood levels of emetine are rarely available, and only one case report describing the intoxication of a 4-year-old child by the chronic administration of ipecac syrup stated an emetine concentration of about 1 μM (500 ng/ml) in the blood (30). In the course of the clinical trials with emetine as an anti-cancer agent the doses were even higher; a single intravenous dose of up to 1.5 mg/kg twice weekly was tolerated (15). Table III.…”

“…to overcome multidrug resistance or to take advantage of synergistic effects in order to minimize side-effects due to the high dosage of other cytotoxic agents. Evidence of emetine's activity against tumor cells first came to light in 1918 (14), and its use in phase I and II clinical cancer trials began over 30 years ago (15)(16)(17)(18)(19). To our knowledge, only one study was performed analyzing emetine in co-treatment with another chemotherapeutic.…”