Universal tolerance of nab-paclitaxel for gynecologic malignancies in patients with prior taxane hypersensitivity reactions / 부인종양

OBJECTIVE: To report on the incidence of nab-paclitaxel hypersensitivity reactions (HSRs) in patients with prior taxane HSR. METHODS: From 2005 to 2015, all patients who received nab-paclitaxel for a gynecologic malignancy were identified. Chart abstraction included pathology, prior therapy, indication for nab-paclitaxel, dosing, response, toxicities including any HSR, and reason for discontinuation of nab-paclitaxel therapy. RESULTS: We identified 37 patients with gynecologic malignancies with a history of paclitaxel HSR who received nab-paclitaxel. Six patients (16.2%) had a prior HSR to both paclitaxel and docetaxel while the other 31 patients had not received docetaxel. No patients experienced a HSR to nab-paclitaxel. Median number of cycles of nab-paclitaxel was 6 (range 2–20). Twelve patients received weekly dosing at 60 to 100 mg/m². The remainder of patients received 135 mg/m² (n=13), 175 mg/m² (n=9), or 225 mg/m² (n=3). Thirty four patients (91.9%) received nab-paclitaxel in combination with carboplatin (n=28, 75.7%), IP cisplatin (n=1, 2.7%), carboplatin and bevacizumab (n=3, 8.1%), or carboplatin and gemcitabine (n=2, 5.4%). Reasons for discontinuing nab-paclitaxel included completion of adjuvant therapy (n=16), progressive disease (n=18), toxicity (n=1), and death (n=1). There were no grade 4 complications identified during nab-paclitaxel administration. Grade 3 complications included: neutropenia (n=9), thrombocytopenia (n=4), anemia (n=1), and neurotoxicity (n=1). CONCLUSION: Nab-paclitaxel is well-tolerated with no HSRs observed in this series of patients with prior taxane HSR. Given the important role of taxane therapy in nearly all gynecologic malignancies, administration of nab-paclitaxel should be considered prior to abandoning taxane therapy.

The impact of combined radiation and chemotherapy on outcome in uterine papillary serous carcinoma compared to chemotherapy alone / 부인종양

OBJECTIVE: To investigate the impact of pelvic radiation on survival in patients with uterine serous carcinoma (USC) who received adjuvant chemotherapy. METHODS: Patients with stage I-IV USC were identified from the Surveillance, Epidemiology, and End Results program 2000 to 2009. Patients were included if treated with surgery and chemotherapy. Patients were divided into two groups: those who received chemotherapy and pelvic radiation therapy (CT_RT) and those who received chemotherapy only (CT). Kaplan-Meier curves and Cox regression proportional hazard models were used. RESULTS: Of the 1,838 included patients, 1,272 (69%) were CT and 566 (31%) were CT_RT. Adjuvant radiation was associated with significant improvement in overall survival (OS; p<0.001) and disease-specific survival (DSS; p<0.001) for entire cohort. These findings were consistent for the impact of radiation on OS (p<0.001) and DSS (p<0.001) in advanced stage (III-IV) disease but not for early stage (I-II) disease (p=0.21 for OS and p=0.82 for DSS). In multivariable analysis adjusting for age, stage, race and extent of lymphadenectomy, adjuvant radiation was a significant predictor of OS and DSS for entire cohort (p=0.003 and p=0.05) and in subset of patients with stage III (p=0.02 and p=0.07) but not for patients with stage I (p=0.59 and p=0.49), II (p=0.83 and p=0.82), and IV USC (p=0.50 and p=0.96). Other predictors were stage, positive cytology, African American race and extent of lymphadenectomy. CONCLUSION: In USC patients who received adjuvant chemotherapy, adjuvant radiation was associated with significantly improved outcome in stage III disease but not for other stages. Positive cytology, extent of lymphadenectomy and African race were significant predictors of outcome.

Prognostic impact of lymphadenectomy in uterine clear cell carcinoma / 부인종양

OBJECTIVE: The aim of this study was to estimate the survival impact of lymphadenectomy in patients diagnosed with uterine clear cell cancer (UCCC). METHODS: Patients with a diagnosis of UCCC were identified from Surveillance, Epidemiology, and End Results (SEER) program from 1988 to 2007. Only surgically treated patients were included. Statistical analysis using Student t-test, Kaplan-Meier survival methods, and Cox proportional hazard regression were performed. RESULTS: One thousand three hundred eighty-five patients met the inclusion criteria; 955 patients (68.9%) underwent lymphadenectomy. Older patients (> or =65) were less likely to undergo lymphadenectomy compared with their younger cohorts (64.3% vs. 75.9%, p10 nodes removed) were 32% (HR, 0.68; 95% CI, 0.56 to 0.83; p<0.001) and 47% (HR, 0.53; 95% CI, 0.43 to 0.65; p<0.001) less likely to die, respectively. CONCLUSION: The extent of lymphadenectomy is associated with an improved survival of patients diagnosed with UCCC.

Lymph node metastasis and pattern of recurrence in clinically early stage endometrial cancer with positive lymphovascular space invasion / 부인종양

OBJECTIVE: To investigate the rate, predictors of lymph node metastasis (LNM) and pattern of recurrence in clinically early stage endometrial cancer (EC) with positive lymphovascular space invasion (LVSI). METHODS: Women with clinically early stage EC and positive LVSI 2005 to 2012 were identified. Kaplan-Meier curves and logistic regression models were used. RESULTS: One hundred forty-eight women were identified. Of them, 25.7% had LNM (21.7% pelvic LNM, 18.5% para-aortic LNM). Among patients with LNM who had both pelvic and para-aortic lymphadenectomy, isolated pelvic, para-aortic and both LNM were noted in 51.4%, 17.1%, and 31.4% respectively. Age and depth of myometrial invasion were significant predictors of LNM in LVSI positive EC. Node positive patients had high recurrence rate (47% vs. 11.8%, p<0.05) especially distant (60.9% vs. 7.9%, p<0.001) and para-aortic (13.2% vs. 1.8%, p=0.017) recurrences compared to node negative EC. LNM was associated with lower progression-free survival (p=0.002) but not overall survival (p=0.73). CONCLUSION: EC with positive LVSI is associated with high risk of LNM. LNM is associated with high recurrence rate especially distant and para-aortic recurrences. Adjuvant treatments should target prevention of recurrences in these areas.

Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells.

BACKGROUND: Sulforaphane (SFN), an isothiocyanate phytochemical present predominantly in cruciferous vegetables such as brussels sprout and broccoli, is considered a promising chemo-preventive agent against cancer. In-vitro exposure to SFN appears to result in the induction of apoptosis and cell-cycle arrest in a variety of tumor types. However, the molecular mechanisms leading to the inhibition of cell cycle progression by SFN are poorly understood in epithelial ovarian cancer cells (EOC). The aim of this study is to understand the signaling mechanisms through which SFN influences the cell growth and proliferation in EOC. RESULTS: SFN at concentrations of 5-20 microM induced a dose-dependent suppression of growth in cell lines MDAH 2774 and SkOV-3 with an IC50 of ~8 microM after a 3 day exposure. Combination treatment with chemotherapeutic agent, paclitaxel, resulted in additive growth suppression. SFN at ~8 microM decreased growth by 40% and 20% on day 1 in MDAH 2774 and SkOV-3, respectively. Cells treated with cytotoxic concentrations of SFN have reduced cell migration and increased apoptotic cell death via an increase in Bak/Bcl-2 ratio and cleavage of procaspase-9 and poly (ADP-ribose)-polymerase (PARP). Gene expression profile analysis of cell cycle regulated proteins demonstrated increased levels of tumor suppressor retinoblastoma protein (RB) and decreased levels of E2F-1 transcription factor. SFN treatment resulted in G1 cell cycle arrest through down modulation of RB phosphorylation and by protecting the RB-E2F-1 complex. CONCLUSIONS: SFN induces growth arrest and apoptosis in EOC cells. Inhibition of retinoblastoma (RB) phosphorylation and reduction in levels of free E2F-1 appear to play an important role in EOC growth arrest.