Increasing the human chorionic gonadotrophin cut-off to ≤1000 IU/l for starting actinomycin D in post-molar gestational trophoblastic neoplasia developing resistance to methotrexate spares more women multi-agent chemotherapy.

BACKGROUND: A human chorionic gonadotropin (hCG) cut-off of ≤300 IU/l for starting actinomycin D (ActD) in post-molar gestational trophoblastic neoplasia (GTN) patients developing methotrexate resistance (MTX-R) reduced the number of women needing toxic multi-agent chemotherapy (etoposide, MTX and ActD alternating weekly with cyclophosphamide and vincristine; EMA/CO) without affecting survival. Here we assess whether an increased hCG cut-off of ≤1000 IU/l spares more women EMA/CO. PATIENTS AND METHODS: All post-molar GTN patients treated with first-line methotrexate and folinic acid (MTX/FA) were identified in a national cohort between 2009 and 2016. Data collected included age, FIGO score, the hCG levels at MTX-R, and treatment outcomes. RESULTS: In total, 609 GTN patients commenced treatment with MTX/FA achieving a complete response in 57% (348/609). Resistance developed in 25.1% (153/609) at an hCG ≤ 1000 IU/l and switching to ActD achieved remission in 92.8% without any major toxicity with the remaining 7.2% remitting on EMA/CO. Comparative analysis of patients switching at an hCG <100 versus 100-300 versus 300-1000 IU/l revealed a significant fall in the cure rate with second-line ActD from 97% (93/96) to 87% (34/39) to 78% (14/18), respectively, P = 0.009. However, by increasing the hCG cut-off from ≤300 to ≤1000 IU/l, 14 patients were spared EMA/CO chemotherapy. Moreover, in the present series, all post-molar GTN remain in remission. CONCLUSION: This study demonstrates that increasing the hCG cut-off from ≤300 to ≤1000 IU/l for choosing patients for ActD following MTX-R spares more women with GTN from the greater toxicity of EMA/CO without compromising 100% survival outcomes.

Impact of isoflurane on malignant capability of ovarian cancer in vitro.

BACKGROUND: Metastatic recurrence of ovarian cancer is the foremost cause of postoperative mortality. With recent research indicating that inhalation of anaesthetics may influence cancer cell behaviour, this study investigated the effects of isoflurane on the expression of tumorigenic markers and proliferative capacity in ovarian cancer cells. METHODS: Ovarian cancer (SK-OV3) cells were cultured and then exposed to 2% isoflurane for 2 h. The expression of markers involved in cell proliferation, angiogenesis, and migration were assessed up to 24 h after treatment using immunofluorescence staining, western blotting, and flow cytometry. The effects of isoflurane on in vitro angiogenesis and migration were also determined. RESULTS: Isoflurane exposure significantly increased insulin-like growth factor (IGF)-1 and IGF-1R expression, cell cycle progression, and cell proliferation in SK-OV3 cells. Increased expression of the angiogenic markers vascular endothelial growth factor (VEGF) by 56% (P<0.05) and angiopoietin-1 by 62% (P<0.05) was also observed 24 h after isoflurane exposure together with an enhanced in vitro angiogenesis. Cell migration was significantly increased after exposure to isoflurane together with increased production of both matrix metalloproteinases 2 and 9 (both P<0.05) by almost five-fold relative to control. These effects were abolished when IGF-1R signalling was blocked either by neutralizing antibody or by small interfering RNA. CONCLUSIONS: Our data indicate that isoflurane increases the malignant potential of ovarian cancer cells through the up-regulation of markers associated with the cell cycle, proliferation, and angiogenesis. This study warrants further investigations.