RESUMO
Objective@#To assess the outcomes and toxic effects of 5-day actinomycin D (Act-D) salvage therapy and to explore the predictors of Act-D resistance in patients with low-risk gestational trophoblastic neoplasia (GTN)who failed 5-day methotrexate (MTX) chemotherapy. @*Methods@#This retrospective study analyzed patients with low-risk GTN administered Act-D salvage therapy after failing MTX chemotherapy at Women's Hospital, School of Medicine Zhejiang University between January 2000 and December 2015. The clinical parameters of these patients were collected and analyzed. @*Results@#The final analysis included 89 cases. Of these, 73 cases (82.02%) responded to salvage Act-D. The remaining 16 resistant cases were switched to etoposide, MTX, Act-D/ cyclophosphamide, and vincristine chemotherapy and achieved complete remission. Serum human chorionic gonadotrophin levels before Act-D salvage therapy (hCG Act-D )in the Act-Dresistant cases were significantly higher than those in the Act-D responders (median 605 vs.103 IU/L, p=0.009). However, the range of hCGAct-D values in Act-D responders was wider than that in Act-D-resistant cases (5.76–16,664 IU/L vs. 11.43–6,732 IU/L). Thus, assigning a general cut-off value was difficult considering the individual setting. Except for 2 cases requiring other salvage regimens due to Act-D toxicity, 97.80% of cases (89/91) tolerated the toxicity. During at least 1-year follow-up, the survival rate was 100.00% and no case developed recurrence. @*Conclusion@#Based on the good therapeutic effect and tolerable toxicity, we recommend Act-D salvage therapy for all patients with low-risk GTN who fail primary MTX chemotherapy.The higher serum hCG levels before Act-D salvage therapy may be associated with resistance to this treatment.
RESUMO
Objective@#To assess the outcomes and toxic effects of 5-day actinomycin D (Act-D) salvage therapy and to explore the predictors of Act-D resistance in patients with low-risk gestational trophoblastic neoplasia (GTN)who failed 5-day methotrexate (MTX) chemotherapy. @*Methods@#This retrospective study analyzed patients with low-risk GTN administered Act-D salvage therapy after failing MTX chemotherapy at Women's Hospital, School of Medicine Zhejiang University between January 2000 and December 2015. The clinical parameters of these patients were collected and analyzed. @*Results@#The final analysis included 89 cases. Of these, 73 cases (82.02%) responded to salvage Act-D. The remaining 16 resistant cases were switched to etoposide, MTX, Act-D/ cyclophosphamide, and vincristine chemotherapy and achieved complete remission. Serum human chorionic gonadotrophin levels before Act-D salvage therapy (hCG Act-D )in the Act-Dresistant cases were significantly higher than those in the Act-D responders (median 605 vs.103 IU/L, p=0.009). However, the range of hCGAct-D values in Act-D responders was wider than that in Act-D-resistant cases (5.76–16,664 IU/L vs. 11.43–6,732 IU/L). Thus, assigning a general cut-off value was difficult considering the individual setting. Except for 2 cases requiring other salvage regimens due to Act-D toxicity, 97.80% of cases (89/91) tolerated the toxicity. During at least 1-year follow-up, the survival rate was 100.00% and no case developed recurrence. @*Conclusion@#Based on the good therapeutic effect and tolerable toxicity, we recommend Act-D salvage therapy for all patients with low-risk GTN who fail primary MTX chemotherapy.The higher serum hCG levels before Act-D salvage therapy may be associated with resistance to this treatment.
RESUMO
A novel targeting drug carrier (FA-BO-PAMAM) based on the PAMAM G5 dendrimer modified with borneol (BO) and folic acid (FA) molecules on the periphery and doxorubicin (DOX) loaded in the interior was designed and prepared to achieve the purposes of enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. 1H NMR was used to confirm the synthesis of FA-BO-PAMAM; its morphology and mean size were analyzed by dynamic light scattering (DLS) and transmission electron microscope (TEM). Based on the HBMEC and C6 cells, cytotoxicity assay, transport across the BBB, cellular uptake and anti-tumor activity in vitro were investigated to evaluate the properties of nanocarriers in vitro. The results showed that the nanocarrier of FA-BO-PAMAM was successfully synthesized, which was spherical in morphology with the average size of (22.28 ± 0.42) nm, and zeta potential of (7.6 ± 0.89) mV. Cytotoxicity and transport across the BBB assay showed that BO-modified conjugates decreased the cytotoxicity of PAMAM against both HBMEC and C6 cells and exhibited higher BBB transportation ability than BO-unmodified conjugates; moreover, modification with FA increased the total uptake of DOX by C6 cells and enhanced the cytotoxicity of DOX-polymer against C6 cells. Therefore, FA-BO-PAMAM is a promising nanodrug delivery system in employing PAMAM as a drug carrier and treatment for brain glioma.