Differential in vitro effects of chemotherapeutic agents on primary cultures of human ovarian carcinoma

Abstract

The treatment of ovarian cancer principally relies on the use of platinum and taxane chemotherapeutic agents. Short-term clinical results have been encouraging, but long-term responses remain limited. In this report, an in vitro assay system that utilizes cells grown from human tumor explants has been used to quantitatively evaluate responses to relevant concentrations of alternative chemotherapeutic agents. The results suggest that there are significant differences in the responses of explant-derived cultured cells to the different agents tested. In an evaluation of 276 primary ovarian cancer specimens, five nonstandard drugs were tested in 51 cases. Of these 51 cases, cyclophosphamide had the highest rate of response at 67%, followed by doxorubicin at 61%, gemcitabine at 49%, etoposide at 48%, and topotecan at 14%. Venn diagrams, representing the in vitro responses to the platins and taxanes, as well as the responses to the nonstandard drugs, illustrate that there clearly are distinct differences among patients in a given population. These data underscore the potential importance of evaluating each patient's response to a number of different drugs to optimize the therapeutic decision-making process.

Progression-free interval in ovarian cancer and predictive value of an ex vivo chemoresponse assay

“…The current study was designed to evaluate the effectiveness of the ChemoFx Ò assay in predicting outcome following chemotherapy in women with ovarian cancer. This assay is designed to select the relevant epithelial ovarian carcinoma cells for testing, to determine the relative cell survival at a range of doses from below to above peak plasma level, to test combinations of drugs, and to determine the degree of response, that is, sensitivity as well as resistance (14)(15)(16)(17)(18) . As such, this assay is designed to identify chemotherapeutic agents to which the patient is likely to be resistant and to identify agents to which the patient's tumor is most likely to be sensitive.…”

“…A possible critique of ex vivo assay-assisted therapy is that it might simply define those tumors that are inherently more likely to be sensitive or resistant to chemotherapy in general, implying that assay-assisted chemotherapy would have no impact on patient outcome. Certainly, previous reports have shown that patients display different degrees of response ex vivo to various chemotherapy agent(s), with a subset being predominantly sensitive or resistant to most agents (9,10,(12)(13)(14)(15)(16)(17)(18) . In the current series, 20% of cases could be considered generally sensitive to chemotherapy and 13% generally resistant while the remaining two thirds of tumor specimens demonstrated considerable heterogeneity of response to the different drug(s) tested.…”

“…Specimens from surgically excised ovarian carcinomas were submitted for testing via the ChemoFx Ò assay as described previously (14)(15)(16)(17)(18) . Briefly, explant specimens were cultured to produce sufficient cell numbers for testing in the assay.…”

Utility of Chemoresponse Assay in Patients Undergoing Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy

“…14 The assay results obtained and reported by Precision Therapeutics are grouped into three categories:…”