Second-Line Treatment with Intravenous Gemcitabine and Oral Etoposide in Platinum-Resistant Advanced Ovarian Cancer Patients: Results of a Phase II Study

Abstract

Objective: The outcome of advanced ovarian cancer patients has not significantly improved since the introduction of platinum. One of the major reasons for this failure is the lack of an effective second-line treatment. In this phase II trial we tested the combination of gemcitabine and etoposide in 2 different groups of patients. Group 1 consisted of patients showing disease progression or relapse within 6 months of first-line platinum-based chemotherapy. Group 2 comprised heavily pretreated patients showing progression during the last chemotherapy attempt. Methods: Thirty-four patients were enrolled. Gemcitabine was administered at a dose of 1,000 mg/m² on days 1 and 8 and etoposide was administered orally at 100 mg/day on days 8–12 for 6 courses. Results: Eighteen patients (52.9%) had an objective response and the median duration of the response was 10.3 months. Our chemotherapy regimen showed a low toxicity and good patient compliance. In 5 patients the treatment had to be delayed and in only 2 patients it was discontinued. Conclusions: The combination of gemcitabine and oral etoposide seems to be a safe and effective second-line treatment for platinum-resistant ovarian cancer patients. Additional data on larger series are warranted to better define the activity of this combination regimen.

PRMT1 Is Recruited via DNA-PK to Chromatin Where It Sustains the Senescence-Associated Secretory Phenotype in Response to Cisplatin

“…We first validated the RNA-seq data by quantitative real-time PCR profiling of a panel of representative SASP genes in both SK-OV-3 (Figure S4C) and HeLa cells ( Figure S4D). Then, we evaluated the role of PRMT1 in SASP onset, following GEM, employed as part of the second-line treatment in platinum-resistant advanced ovarian cancer patients (Bruzzone et al, 2011). GEM triggered IL1A, IL1B, and IL6 transcription, which was however abrogated in PRMT1-knockdown cells ( Figure S4E).…”

Fluorescence Detection of Etoposide Encapsulated Mesoporous Silica Nanoparticles by Environmentally Benign Bioanalytical HPLC Method and its Application to Pharmacokinetic Study

“…Etoposide (ETD) is a widely used anticancer drug in treatment of cancers of prostate, 1 lung, 2,3 lymph 4 and ovary. 5,6 The mechanism of action is based on inhibition of topoisomerase-II and activation of redox reactions which will produce derivatives which will cause DNA damage. 7 However, ETD belongs to Biopharmaceutical Classification System (BCS) Class IV and suffers from both solubility and permeability limitations.…”

Epithelial Ovarian Cancers: On-Target is Better than Near-Target

“…The outcome of relapsed ovarian cancer remains poor inspite of many permutations -combinations being tried. The commonly used drugs are gemcitabine, pegylated liposomal doxorubicin, irinotecan and etoposide, trabectedin [9][10][11][12][13][14][15] which has shown increment in progression free survival or clinical benefit.…”