Patients' and oncologists' preferences for second-line maintenance PARP inhibitor therapy in epithelial ovarian cancer.

Aim: To understand the preferences of US patients and oncologists for PARP inhibitors as second-line maintenance (2LM) for epithelial ovarian cancer. Methods: A discrete choice experiment was conducted to assess the preferences of treatment attributes. Results: The most valued attributes were risk of grade 3/4 adverse events (AEs; patients, n = 204) and progression-free survival (PFS; oncologists, n = 151). To accept a 37% increased risk of grade 3/4 AEs, PFS would need to increase by 27.9 months (patients) and 6.3 months (oncologists). The least valued attributes were dosing form/frequency (patients) and grade 3/4 anemia risk (oncologists). Conclusion: Patients' and oncologists' willingness to make benefit-risk trade-offs in the 2LM setting suggests that the PFS gains observed in selected studies of poly (ADP-ribose) polymerase inhibitors in BRCA-mutated disease are worth the toxicity risk.

Plain language summary Maintenance therapy is a treatment option intended to keep ovarian cancer from coming back or getting worse for as long as possible after responding to chemotherapy. PARP inhibitors are a new type of maintenance therapy for ovarian cancer. This study aimed to understand the patients' and physicians' preferences for the benefits and risks associated with different PARP inhibitors used as maintenance therapy for ovarian cancer. Participants were asked to compare various treatment options based on their different safety profiles, effectiveness and form of medication (e.g., three capsules by mouth once a day versus two tablets by mouth twice a day), and then choose the treatment they most preferred. Through this exercise, the treatment features that mattered most to patients and physicians were identified. The most important treatment feature for patients was decreasing the chance of experiencing a serious side effect that requires medical intervention or hospitalization. In contrast, physicians valued lengthening the time that a cancer remains stable and does not worsen. To accept a 37% higher chance of experiencing a side effect that requires medical intervention or hospitalization, patients expect their cancer to remain stable and not worsen for an additional 28 months. This was a large difference from the 6 months that the physicians would consider as acceptable. The least important treatment features for patients are the amount of pills required per dose, the form of the given medication (e.g., tablet vs capsule) and the schedule of taking the treatment. On the other hand, physicians were least concerned about lowering the risk of experiencing low blood counts that, requiring medical intervention.

Glutathione-S-transferases and Chemotherapy Resistance of Hodgkin's Lymphoma Cell Lines.

BACKGROUND: Glutathione-S-transferases (GSTs) are associated with multidrug resistance of tumor cells and are involved in drug detoxification and control of apoptosis. We analyzed the impact of GSTs on apoptosis of Hodgkin's lymphoma (HL) cells. MATERIALS AND METHODS: Expression of GST isoforms in HL cell lines was assessed by analysis of DNA microarray data and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The impact of the GST inhibitor ethacrynic acid (EA) on HL cell survival was analyzed in vitro. RESULTS: DNA microarray analysis and qRT-PCR analysis demonstrated higher expression of GST isoforms in chemoresistant HL cells. Therefore, GSTs may contribute to chemoresistance of HL cells. Incubation of GST-expressing chemoresistant L-1236 HL cells with EA significantly enhanced the activity of cisplatin against these cells. CONCLUSION: Our data suggest that the combined treatment with chemotherapy and GST inhibitors such as EA might be an interesting option for patients with chemoresistant HL.