Metronomic chemotherapy as a palliative treatment in poor performance status patients with advanced epithelial ovarian carcinoma

Abstract

Ovarian cancer is the ninth most common cancer among women, excluding non-melanoma skin cancer. It ranks the fifth in cancer deaths among women, accounting for more deaths than any other cancers of female reproductive system [1] .Current treatment of ovarian cancer entails a combination of surgery and chemotherapy. Currently the 1st line chemotherapy consists of a combination of carboplatin and paclitaxel to which approximately 80% of women respond [2] .Despite aggressive surgery and chemotherapy more than 80% of patients will relapse and then be treated with the second line chemotherapy with objective response in about 20% of cases and with lower percentages of complete responses. These results make the main goal of the 2nd and 3rd line chemotherapies are only palliation with the hope to prolong time to progression and to improve quality of life [3] .Several chemotherapeutic regimens have been used as a single agent in phase II trials with patients previously treated with cisplatin, such as paclitaxel, gemcitabine, doxorubicin, the objective response rate ranging from 10%-50% with different toxicity profiles [4] .The dose-dense chemotherapy regimen was used in some trials which mean that the total dose of chemotherapy agent was actually higher than the dose which was given in standard treatment. This increase was associated with some toxic side effects that caused treatment delays and modifications. More than half of the women in the dose dense group discontinued treatment early and most of them did so because of the toxicity [5] .Experimental studies have shown that certain cytotoxic agents when administered at low and frequent doses are more effective in targeting tumor endothelium than large single bolus doses followed by long rest period. This is because intra-tumoral vascular endothelial cells, in contrast to the endothelium of quiescent mature blood vessels of normal adult tissues, proliferating rapidly and are vulnerable to cytotoxic agents. While the long interval between cycles of conventional chemotherapy permits the survival and re-growth of a small number of endothelial cells allowing tumor angiogenesis to persist [6] .Metronomic chemotherapy is based on the chronic administration of chemotherapeutic agents at relatively low, minimally toxic doses with no prolonged drug free breaks. Metronomic chemotherapy was originally, developed to overcome drug resistance by shifting the therapeutic target from tumor cells to the tumor vasculature [7] .Continuous, low dose chemotherapy enhances antiangiogenic effect of some cytotoxic agents and may also enhance pro-apoptotic effect in both dividing tumor cells and endothelial cells, so low dose of chemotherapy has Abstract Objective: The aim of our study was to evaluate the clinical efficacy and tolerability of metronomic chemotherapy in patients with advanced ovarian carcinoma. Methods: Fifteen patients with advanced ovarian carcinoma and bad performance status were subjected to daily cyclophosphamide (CTX) after failure of 1st line chemotherapy which inc...