One-Day Versus Three-Day Dexamethasone in Combination with Palonosetron for the Prevention of Chemotherapy-Induced Nausea and Vomiting: A Systematic Review and Individual Patient Data-Based Meta-Analysis.

BACKGROUND: A dexamethasone-sparing regimen consisting of palonosetron plus 1-day dexamethasone for the prevention of chemotherapy-induced nausea and vomiting (CINV) has been studied previously. Here, we evaluate the noninferiority of the dexamethasone-sparing regimen in overall antiemetic control using a meta-analysis based on individual patient data (IPD). MATERIALS AND METHODS: We conducted a systematic review for randomized trials reporting CINV outcomes for the comparison of palonosetron plus 1-day dexamethasone (d1 arm) versus the same regimen followed by dexamethasone on days 2-3 after chemotherapy (d3 arm) in chemotherapy-naïve adult patients undergoing either moderately emetogenic chemotherapy (MEC) or anthracycline plus cyclophosphamide (AC)-containing chemotherapy. PubMed and MEDLINE were searched electronically. A manual search was also conducted. The primary endpoint was complete response (CR; no emesis and no rescue medication) in the overall 5-day study period. The noninferiority margin was set at -8.0% (d1 arm-d3 arm). RESULTS: Five studies (n = 1,194) were eligible for analysis and all IPD was collected. In the overall study period, the d1 arm showed noninferiority to the d3 arm for CR as well as complete control (pooled risk difference in CR rate - 1.5%, 95% confidence interval [CI] -7.1 to 4.0%, I2 = 0%; in complete control rate - 2.4%, 95% CI -7.7 to 2.9%, I2 = 0%). There was no significant interaction between dexamethasone regimen and risk factors (type of chemotherapy, sex, age, and alcohol consumption). CONCLUSION: This IPD meta-analysis indicates that the dexamethasone-sparing regimen is not associated with a significant loss in overall antiemetic control in patients undergoing MEC or AC-containing chemotherapy, irrespective of known risk factors for CINV. IMPLICATIONS FOR PRACTICE: Although dexamethasone in combination with other antiemetic agents has been used to prevent chemotherapy-induced nausea and vomiting (CINV), it is of clinical importance to minimize total dose of dexamethasone in patients undergoing multiple cycles of emetogenic chemotherapy. This individual-patient-data meta-analysis from five randomized controlled trials (1,194 patients) demonstrated a noninferiority of the dexamethasone-sparing regimen for complete response and complete control of CINV. The outcomes were comparable across patients with different characteristics. These findings thus help physicians minimize use of the steroid and further reduce the burden of dexamethasone-related side effects in patients undergoing multiple consecutive courses of emetogenic chemotherapy.

Phase I study on pegylated liposomal doxorubicin in combination with docetaxel for patients with platinum-resistant or partially platinum-sensitive epithelial ovarian cancer: The Kansai Clinical Oncology Group study.

CONTEXT: In platinum-resistant ovarian cancer, single-agent chemotherapy is recommended for the reduction of adverse events. However, in clinical practice, some patients can tolerate drug-specific adverse events. AIMS: We assessed the safety of pegylated liposomal doxorubicin (PEG-LD) and docetaxel regimen in the first cycle of ovarian cancer. SETTINGS AND DESIGN: We performed a phase I study to evaluate the combination therapy of PEG-LD and docetaxel. MATERIALS AND METHODS: We recruited five patients with recurrent ovarian cancer within 12 months of first-line platinum-based chemotherapy. All patients had measurable disease severity. PEG-LD and docetaxel were intravenously administered on day 1 and every 21 days using three dose levels: 25 mg/m2 PEG-LD and 50 mg/m2 docetaxel; 30 mg/m2 PEG-LD and 50 mg/m2 docetaxel; and 30 mg/m2 PEG-LD and 60 mg/m2 docetaxel. STATISTICAL ANALYSIS USED: We defined the maximum tolerated dose of the combination therapy based on the modified Fibonacci method. RESULTS: Five patients were enrolled in this study. The median treatment-free interval was 5.5 months. Two dose-limiting toxicities (Grade 4 neutropenia) were observed in two patients. One complete response, one partial response, one stable disease, and two progressive disease cases were observed. The overall response rate was 2/5, and the disease control rate was 3/5. The median overall survival was 7.4 months. CONCLUSIONS: We determined that 25 mg/m2 of PEG-LD and 50 mg/m2 of docetaxel were safe and effective doses. This preliminary efficacy and safety data should be further investigated in a Phase II trial.

Effectiveness of antiemetic triplet therapy with aprepitant, palonosetron, and dexamethasone for gynecologic cancer patients receiving carboplatin and paclitaxel: a prospective single-arm study.

PURPOSE: There is no positive evidence for the efficacy of antiemetic triplet therapy with aprepitant (APR), palonosetron (PALO), and dexamethasone (DEX) for moderate emetogenic chemotherapy, especially for gynecologic malignancies. Thus, the present study evaluated the efficacy of this triplet therapy in patients receiving carboplatin and paclitaxel (CP) for gynecologic malignancy. METHODS: Seventy patients with gynecologic cancer receiving CP were enrolled into a prospective single-arm study with APR (125 mg on day 1, 80 mg on days 2-3), PALO (0.75 mg), and DEX (20 mg) before initiating chemotherapy. The primary endpoint was delayed complete response (CR) rate, i.e., no vomiting and no rescue, at 24-120 h after chemotherapy administration. RESULTS: Seventy patients were enrolled. The delayed CR rate was 97.1% (68/70). No serious adverse events were observed. Younger patient age (≤50 years) tended to be associated with a poor delayed CR rate. CONCLUSIONS: This study demonstrated a notable efficacy of antiemetic triplet therapy with APR, PALO, and DEX in female patients receiving CP. Further evaluation with a larger phase III trial is warranted.

Clinical Significance of Tissue Factor Pathway Inhibitor 2, a Serum Biomarker Candidate for Ovarian Clear Cell Carcinoma.

BACKGROUND: There is currently no reliable serum biomarker for ovarian clear cell carcinoma (CCC), a highly lethal histological subtype of epithelial ovarian cancer (EOC). Previously, using a proteome-based approach, we identified tissue factor pathway inhibitor 2 (TFPI2) as a candidate serum biomarker for CCC. In this study, we sought to evaluate the clinical diagnostic performance of TFPI2 in preoperative prediction of CCC. METHODS: Serum TFPI2 levels were measured in serum samples from a retrospective training set consisting of patients with benign and borderline ovarian tumors, EOC subtypes, and uterine diseases. Via receiver operating characteristic (ROC) analyses, we compared the diagnostic performance of TFPI2 with that of CA125 in discrimination of patients with ovarian CCC from other patient groups. The observed diagnostic performances were examined in a prospective validation set. RESULTS: The 268-patient training set included 29 patients with ovarian CCC. Unlike CA125, which was also elevated in patients with endometriosis and several EOC subtypes, serum TFPI2 levels were specifically elevated only in ovarian CCC patients, consistent with the mRNA expression pattern in tumor tissues. The area under the ROC curve (AUC) of serum TFPI2 was obviously higher than that of CA125 for discrimination of CCC from other ovarian diseases (AUC = 0.891 versus 0.595). Applying a cut-off value of 280 pg/mL, TFPI2 could distinguish early-stage (FIGO I and II) CCC from endometriosis with 72.2% sensitivity, 93.3% specificity, and 88.8% accuracy. Similar results were confirmed in an independent 156-patient prospective validation set. CONCLUSIONS: TFPI2 is a useful serum biomarker for preoperative clinical diagnosis of CCC.

Evaluation of TOP2A as a Predictive Marker for Endometrial Cancer With Taxane-Containing Adjuvant Chemotherapy.

OBJECTIVE: Paclitaxel plus carboplatin and doxorubicin plus cisplatin are usually selected as adjuvant chemotherapy for endometrial cancer. However, biomarkers that can determine the appropriate chemotherapy regimen are not known. In the present study, we performed a retrospective investigation of the association between TOP2A, HER2 overexpression, and disease-free and overall survival in patients with endometrial cancer receiving taxane and platinum. METHODS: Eligible patients had a diagnosis of endometrial cancer based on histology and treated with an adjuvant chemotherapy regimen comprising taxane-platinum after surgery, and the HER2 and TOP2A status of the endometrial cancer regions was determined. Overall survival and disease-free survival between HER2 status and TOP2A status were estimated by the Kaplan-Meier method and compared using the log-rank test. RESULTS: We identified 56 patients who fulfilled the previously described criteria. Median follow-up was 49 months (range, 18-110 months). HER2-positive tumors were detected in 11 patients (19.6%), and TOP2A-positive tumors were detected in 7 patients (12.5%). Overall survival was not significantly different between patients with HER2-positive tumors and those with HER2-negative tumors, although disease-free survival for patients with HER2-positive tumors was significantly lower than disease-free survival for patients with HER2-negative tumors (P = 0.049). In contrast, patients with TOP2A-positive tumors had significantly lower overall survival than did patients with TOP2A-negative tumors (P = 0.020), and disease-free survival for patients with TOP2A-positive tumors tended to be shorter than for those with TOP2A-negative tumors. CONCLUSIONS: Patients with TOP2A overexpression have a worse prognosis compared with those with TOP2A nonexpression, and TOP2A may be a useful biomarker in patients receiving adjuvant taxane-platinum regimens with moderate- to high-risk endometrial cancer.

Palonosetron in combination with 1-day versus 3-day dexamethasone to prevent nausea and vomiting in patients receiving paclitaxel and carboplatin.

PURPOSE: The aim of the present study was to evaluate the efficacy and toxicity of palonosetron (PAL) and dexamethasone (DEX) on day 1 only in patients with gynecologic cancer receiving paclitaxel combined with carboplatin (TC). The primary endpoint was to evaluate the complete response (CR) rate in the delayed phase. METHODS: This study was a randomized phase 2. Regardless of assignment to either study arm, all patients received an intravenous prophylactic regimen of DEX (20 mg) within 15 min and then an intravenous dose of PAL (0.75 mg) as a bolus given 30 min before initiation of TC on day 1. Patients in the DEX 1-day group received no additional DEX on days 2 and 3. Patients in the DEX 3-day group received DEX (8 mg) orally on days 2 and 3. RESULTS: Eighty-two patients had evaluable data on the primary outcome. The CR rates in the delayed phase between the two groups were not statistically significantly different (3-day group, 76.9 % [30/39]; 1-day group 69.8 % [30/43]; p = 0.4652). The frequency of constipation and insomnia which were antiemetic treatment-related adverse events was similar between two groups, and no serious adverse events occurred. CONCLUSIONS: Administration of a combination of PAL and DEX 1 day may prevent chemotherapy-induced nausea and vomiting (CINV) in the delayed phase for TC as well as administration of DEX 3 days. Further evaluation of the antiemetic regimen of combination of PAL and DEX 1 day for TC is warranted in future phase 3 trials.

Immature teratoma after three laparoscopic resections for mature cystic teratomas.

We report a case in which an immature teratoma developed following three previous resections for mature cystic teratomas. The patient was a 26-year-old nulliparous woman with a regular menstrual cycle. Twelve years earlier, she had consulted a pediatrician for complaints of lower abdominal pain. Bilateral cystic teratomas were suspected and she underwent a left salpingo-oophorectomy and a right cystectomy laparoscopically, and bilateral mature cystic teratomas were diagnosed histologically. She underwent a right cystectomy twice afterwards and mature cystic teratomas were diagnosed. Three years after the third surgery, a regular checkup performed annually for ovarian cyst recurrence revealed a 9.3 cm ovarian cyst by ultrasonography without marker elevation or complaint of symptoms. Magnetic resonance imaging (MRI) showed a 10 cm multilocular cyst, including a part with heterogeneous medium and high-signal intensity on T2-weighted images, which revealed enhancement on dynamic contrast-enhanced MRI unlike the previous images. Ovarian tumors, including immature teratomas and malignancy, were considered. She had a strong wish to undergo laparoscopic surgery. She was diagnosed with an immature teratoma, grade 1 of the right ovary. Although the frequency of recurrence of immature teratomas after resection of mature cystic teratomas is very low, regular checkups are necessary because there may be no associated symptoms.

Evaluation of the relation between patient characteristics and the state of chemotherapy-induced nausea and vomiting in patients with gynecologic cancer receiving paclitaxel and carboplatin.

PURPOSE: An antiemetic regimen for patients taking paclitaxel and carboplatin (TC) includes dexamethasone (20 mg) to protect against hypersensitivity. Chemotherapy-induced nausea and vomiting (CINV), however, is difficult to adequately control in patients receiving TC. In the present study, we retrospectively investigated risk factors for CINV in patients receiving TC with this antiemetic regimen based on a questionnaire. METHODS: Eligible patients were diagnosed with gynecologic cancer and receiving paclitaxel (175 mg/m(2)) intravenously for 3 h and carboplatin (area under the curve 5 mg/mL per min) on day 1 every 3 weeks in our institution, and treated with granisetron (3 mg) and dexamethasone (20 mg) for antiemesis. Data of nausea and vomiting assessed by Common Terminology Criteria for Adverse Events version4.0 were collected from the medical records. Patients were asked to complete a questionnaire including items such as age and hyperemesis. Logistic regression analysis was used to evaluate univariate and independent multivariate associations with items on nausea of grade 2 or greater and vomiting of grade 1 or greater. RESULTS: On univariate logistic analysis, no item was significantly associated with nausea of grade 2 or greater. Hypertension and hyperemesis gravidarum and adjuvant chemotherapy were significantly associated with delayed vomiting of grade 1 or greater. Multivariate analysis was performed with delayed vomiting of grade 1 or greater as an endpoint, and the resulting independent items were hypertension and hyperemesis gravidarum. CONCLUSIONS: The present study showed that the risk factor for delayed vomiting of grade 1 or higher was a history of hyperemesis gravidarum in patients receiving conventional TC with dexamethasone (20 mg) and granisetron. Therefore, in patients with this risk factor, criteria of major organizations should be followed first.

Port-site metastasis of mucinous borderline ovarian tumor after laparoscopy.

We report a case of port-site metastasis after laparoscopic surgery for borderline mucinous ovarian tumors (mBOTs) without spillage and review the related literature. The patient was a 50-year-old nulligravida who presented with abdominal distension. Magnetic resonance imaging showed a 20 × 10-cm multilocular mass with various signal intensities. The wall and septa of the mass were neither thick nor enhanced. A laparoscopy was performed. An intact left ovarian tumor was observed. The weight of the tumor was 1,540 g. The final diagnosis was stage IA intestinal-type mBOT, so the patient did not undergo adjuvant therapy. Twenty-six months after surgery, the patient presented with a 3 × 5-cm palpable mass on the umbilicus. Biopsy of the mass revealed mucinous adenocarcinoma and computed tomography showed a 3.5 × 4.0-cm mass at the umbilicus without additional metastases. A laparotomy was performed and no metastasis in the peritoneal cavity was observed by gross examination. An umbilical mass resection, hysterectomy, right salpingo-oophorectomy, appendectomy, and partial omentectomy were performed. Hematoxylin and eosin-stained sections of the umbilical mass revealed glands of varying size infiltrating the stroma, immunohistologic staining for cytokeratin 7 was positive, and cytokeratin 20 was negative, but no other metastases were observed. The patient was diagnosed with port-site metastasis and invasive recurrence of mBOT. She underwent six cycles of adjuvant paclitaxel and carboplatin therapy. Large ovarian tumors should be carefully extracted without spillage of the tumor contents to prevent port-site metastasis, despite the low incidence.

Successful laparoscopic management of a primary omental pregnancy: case report and review of literature.

A 32-year-old gravid 1, parity 0 woman was referred to our hospital with suspicion of ectopic pregnancy 31 days after her previous menstrual period. She had a 5-month history of secondary infertility reported increasing lower abdominal pain. Her serum human chronic gonadotropin level was 8160 mIU/mL. Her medical history was significant for a myomectomy and an enucleation of left ovarian cyst. On suspicion of an ectopic pregnancy, laparoscopic exploration was performed. Dense pelvic adhesion was seen. After dissection of the adhesion, we could not find the blastocyst in her pelvis. Early pregnancy tissue implanted in the omentum was identified and was excised laparoscopically. The postoperative course was uneventful. When no ectopia is found in the fallopian tubes during laparoscopy or laparotomy for ectopic pregnancy, all peritoneal surfaces and the omentum must be carefully inspected during surgery.

Risk factors for wound complications after surgery for gynecologic malignancies.

INTRODUCTION: Factors in wound complications such as surgical duration and suture methods are surgeon-side problems. The purpose of the present study was to retrospectively evaluate the incidence of wound complications in patients who underwent wound closure with stainless steel staples or subcuticular sutures in surgery for gynecologic malignancies and to retrospectively determine the risk factors for wound complications. PATIENTS AND METHODS: From April 2007 through March 2012, a cohort of 317 consecutive patients undergoing surgery for gynecologic malignancies was evaluated in the retrospective study. The skin was closed with stainless steel staples before March 2010 (staples group). From April 2010, the skin was closed by subcuticular suturing (subcuticular group). We compared the incidence of wound complications between 2 groups and evaluated independent multivariate associations with the effect of clinical parameters on occurrence of wound complications. RESULTS: The incidence of wound disruption was 7.3% (23/317): 12.1% (17/140) in the staples group and 3.4% (6/177) in the subcuticular group (P = 0.0029). The incidence of wound infection was 2.5% (8/317): 5.0% (7/140) in the staples group and 0.6% (1/177) in the subcuticular group (P = 0.0124). Multivariate analyses performed with wound disruption as the end point revealed long-term steroid treatment, subcutaneous thickness, and skin staples as independent predictors. Subcutaneous thickness and skin staples were independent factors significantly associated with the possibility of wound infection. CONCLUSION: The findings of the present study indicated that risk factors for wound complications after surgeries for gynecologic malignancies include, as a surgeon-side problem, the use of staples for skin closure, and as a patient-side problem, a subcutaneous thickness of more than 30 mm.

Posttreatment cut-off levels of squamous cell carcinoma antigen as a prognostic factor in patients with locally advanced cervical cancer treated with radiotherapy.

OBJECTIVE: The aim of the present study was to assess prognostic factors for patients with locally advanced cervical cancer treated with radiotherapy as the primary treatment and to assess the posttreatment cut-off levels of squamous cell carcinoma antigen (SCC-Ag) to predict three-year overall survival (OS) rates. METHODS: One hundred and twenty-eight patients with cervical squamous cell carcinoma (International Federation of Gynecology and Obstetrics [FIGO] stage IIB-IVA) treated using radiotherapy or concurrent chemoradiotherapy were identified. Of these patients, 116 who had SCC-Ag levels >1.5 ng/mL prior to treatment were analyzed retrospectively. RESULTS: Median age was 68 years (range, 27 to 79 years). The complete response rate was 70.7% and the three-year OS rate was 61.1%. The median levels of pretreatment and posttreatment SCC-Ag were 11.5 ng/mL (range, 1.6 to 310.0 ng/mL) and 0.9 ng/mL (range, 0.4 to 41.0 ng/mL), respectively. Multivariate analysis showed that pretreatment anemia (p=0.041), pelvic lymph node metastasis (p=0.016) and posttreatment SCC-Ag levels (p=0.001) were independent prognostic factors for three-year OS. The SCC-Ag level cut-off point for three-year OS rates, calculated using a receiver operating characteristic curve, was 1.15 ng/mL (sensitivity, 80.0%; specificity, 74.0%). CONCLUSION: Pretreatment anemia and pelvic lymph node metastasis are poor prognostic factors in locally advanced cervical cancer. Furthermore, posttreatment SCC-Ag levels <1.15 ng/mL predicted better three-year OS rates.

Malignant Transformation from Endometriosis to Atypical Endometriosis and Finally to Endometrioid Adenocarcinoma within 10 Years.

Atypical endometriosis is reported to possess a precancerous potential attributed to premalignant changes characterized by cytological atypia and architecture proliferation. Moreover, the coexistence of atypical endometriosis and neoplasms had been reported. However, cases of atypical endometriosis transformation to carcinoma are rarely reported. We describe the case of a 33-year-old woman who had a long therapeutic history of endometriosis. Three laparoscopic surgeries were performed to treat endometriosis. After the third surgery, she was diagnosed as having grade 1 endometrioid adenocarcinoma. The histological review of the previous surgery confirmed the diagnosis of atypical endometriosis based on the second specimen. The patient's disease progressed from a benign endometriotic cyst to atypical endometriosis and finally to endometrioid adenocarcinoma within 10 years. When we encounter cases of atypical endometriosis, it is necessary to consider the possibility of ovarian cancer and carefully follow the patients for long periods.

CA-125 cut-off value as a predictor for complete interval debulking surgery after neoadjuvant chemotherapy in patients with advanced ovarian cancer.

OBJECTIVE: In the present study, we evaluated changes in CA-125 cut-off values predictive of complete interval debulking surgery (IDS) after neoadjuvant chemotherapy (NAC) using receiver operating characteristic (ROC) analysis. METHODS: This retrospective single-institution study included patients with International Federation of Gynecology and Obstetrics (FIGO) stage III epithelial ovarian cancer and a pre-NAC serum CA-125 level of greater than 40 U/mL who were treated with neoadjuvant platinum-based chemotherapy followed by IDS between 1994 and 2009. Logistic regression analysis was used to evaluate univariate and independent multivariate associations with the effect of clinical, pathological, and CA-125 parameters on complete IDS, and ROC analysis was used to determine potential cut-off values of CA-125 for prediction of the possibility of complete IDS. RESULTS: Seventy-five patients were identified. Complete IDS was achieved in 46 (61.3%) patients and non-complete IDS was observed 29 (38.7%). Median pre-NAC CA-125 level was 639 U/mL (range, 57 to 6,539 U/mL) in the complete IDS group and 1,427 U/mL (range, 45 to 10,989 U/mL) in the non-complete IDS group. Median pre-IDS CA-125 level was 15 U/mL (range, 2 to 60 U/mL) in the complete IDS group and 53 U/mL (range, 5 to 980 U/mL) in the non-complete IDS group (p<0.001). Multivariate analyses performed with complete IDS as the endpoint revealed only pre-IDS CA-125 as an independent predictor. The odds ratio of non-complete IDS was 10.861 when the pre-IDS CA-125 level was greater than 20 U/mL. CONCLUSION: The present data suggest that in the setting of IDS after platinum-based NAC for advanced ovarian cancer, a pre-IDS CA-125 level less than 20 U/mL is an independent predictor of complete IDS.

Comparison of Neoadjuvant Intraarterial Chemotherapy Versus Concurrent Chemoradiotherapy in Patients With Stage IIIB Uterine Cervical Cancer.

BACKGROUND: The purpose of this study was to compare the long-term survival of patients with stage IIIB squamous cell carcinoma of the cervix treated with neoadjuvant intraarterial chemotherapy (IA-NAC) versus those treated with concurrent chemoradiotherapy (CCRT). METHODS: We retrospectively reviewed the clinical records of 38 patients with stage IIIB squamous cell carcinoma of the cervix admitted between January 1994 and December 1999 who received IA-NAC followed by abdominal radical hysterectomy (ARH) or radiotherapy (RT). IA-NAC consisted of bilateral infusion via the internal iliac artery of cisplatin, bleomycin and pirarubicin for 2-3 courses. A historical control group of 64 patients who underwent primary CCRT from January 2000 to September 2007 was used for comparison. RESULTS: In the IA-NAC group, 12 patients (31.6%) with operable tumors underwent ARH, and the remaining 26 patients (68.4%) received RT. The response rates were 86.8% (12 complete response + 21 partial response) for IA-NAC and 98.4% (26 complete response + 37 partial response) for CCRT (P = 0.077), respectively. The 5-year overall survival and disease-free survival rates were 62.4 and 44.5% for IA-NAC and 51.1 and 46.9% for CCRT (P = 0.247 and 0.776), respectively. The 5-year overall survival and disease-free survival rates were 75.0 and 58.3% for the patients receiving IA-NAC followed by ARH, and 55.3 and 37.6% for the patients receiving IA-NAC followed by RT (P = 0.368 and 0.262), respectively. CONCLUSIONS: In the present study, IA-NAC followed by ARH or RT and primary CCRT showed similar survival rates for stage IIIB squamous cell carcinoma of the cervix.

Modulation of estrogenic action in clear cell carcinoma of the ovary (Review).

Two histologic types, clear cell carcinoma (CCC) and endometrioid adenocarcinoma (EAC), are the common histology in ovarian cancer patients who have associated endometriosis. However, both tumor types have distinct clinicopathological characteristics and molecular phenotypes. EAC is predominantly positive for estrogen receptor (ER), but CCC specifically exhibits lower ER expression. This study reviews the current understanding of the role of the ER information in the pathogenesis of CCC, as well as the English language literature for biochemical studies on ER expression and estrogenic action in CCC. The iron-mediated oxidative stress occurs due to repeated hemorrhage in endometriosis, then this compound oxidatively modifies genomic DNA and, subsequently, ER depletion may be observed. There are a number of factors that interfere with ER expression and estrogen activity, which include DNA methylation of the promoter region, histone deacetylation, heme and iron binding, chromatin remodeling and ubiquitin ligase activity. Loss of estrogen function may be a turning point in CCC progression and aggressiveness.

Phase II trial of paclitaxel and nedaplatin in patients with advanced/recurrent uterine cervical cancer: a Kansai Clinical Oncology Group study.

OBJECTIVE: A multicenter phase II trial was conducted to evaluate the activity and toxicity of paclitaxel and nedaplatin (cis-diammineglycolatoplatonum) in patients with advanced/recurrent uterine cervical cancer. METHODS: Patients were required to have measurable disease. Histologic confirmation of the primary diagnosis as uterine cervical cancer was mandatory. The treatment consisted of paclitaxel 175 mg/m(2) over 3 hours and nedaplatin 80 mg/m(2) intravenously over 1 hour on day 1 every 28 days until progressive disease or adverse effects prohibited further therapy. RESULTS: Fifty patients were enrolled into the study protocol from October 2007 to February 2010. 45 patients(90%) were eligible for assessment of response (RECIST version 1.0) to treatment; 31 patients (62%) received prior radiotherapy and 23 patients (46%) received prior chemotherapy. The overall response rate was 44.4% (11 complete responses and 8 partial responses) with 22.2% of patients having stable disease. Grades 3 or 4 adverse events (NCI-CTCAE ver 3) included neutropenia (n=16, 32.7%), febrile neutropenia (n=1, 2.0%), anemia (n=9, 18.4%), but there was no significant thrombocytopenia. Non-hematologic toxicity was generally not serious and without a dominant pattern. The median progression-free survival was 7.5 months (95% C.I., 5.7, 9.4) and overall survival was 15.7 months (95% C.I., 9.4, 21.9). CONCLUSIONS: Paclitaxel 175 mg/m(2) and nedaplatin 80 mg/m(2) intravenously on day 1 every 28 days in patients with advanced/recurrence uterine cervical cancer demonstrated easy administration, favorable antitumor activity, and the toxicity profile of this regimen would be decreased compared with cisplatin-containing combinations. Evaluation of this regimen in phase III trials is warranted.

Molecular mechanisms linking endometriosis under oxidative stress with ovarian tumorigenesis and therapeutic modalities.

Inflammation plays a role in the pathogenesis of endometriosis. Endometriosis-associated ovarian carcinogenesis might be promoted through oxidative stress-induced increased genomic instability, aberrant methylation, and aberrant chromatin remodeling, as well as mutations of tumor suppressor genes. Aberrant expression of ARID1A, PIK3CA, and NF-kB genes has been recognized as the major target genes involved in oxidative stress-induced carcinogenesis. HNF-1beta appears to play a key role in anti-oxidative defense mechanisms. We discuss the pathophysiologic roles of oxidative stress as somatic mutations as well as highly specific agents that effectively modulate these targets.

Cut-off value of D-dimer for prediction of deep venous thrombosis before treatment in ovarian cancer.

OBJECTIVE: The purpose of the present study was to elucidate the incidence of deep venous thrombosis (DVT) before treatment in ovarian cancer and the appropriate cut-off value of D-dimer (DD) for the diagnosis of DVT. METHODS: Between July 2007 and October 2008, eighty seven patients with presumed ovarian cancer (final diagnosis: ovarian cancer, n=59; borderline malignancy, n=28) were enrolled. Measurement of DD levels and subsequent venous ultrasonography were performed before treatment. RESULTS: The mean DD level was 4.1 µg/mL. Subsequent venous ultrasonography revealed DVT in 14 of 87 (16.1%) patients (ovarian cancer, 12 cases; borderline malignancy, 2 cases). None were found to have developed DVT if they had a DD level of <1.5 µg/mL. If 1.5 µg/mL was used as a cut-off value for DD levels to diagnose DVT, sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 61.6%, 33.3%, and 100%. There was noclinical onset of postoperative pulmonary thromboembolism. CONCLUSION: Our data suggest that presumed ovarian cancer patients with at least more than 1.5 µg/mL should be examined using venous ultrasonogaphy to detect DVT.