Intraoperative intraperitoneal chemotherapy with cisplatin in epithelial ovarian cancer.

OBJECTIVE: To assess retrospectively the feasibility of intraoperative intraperitoneal (IP) chemotherapy with cisplatin in epithelial ovarian cancer. METHODS: IP chemotherapy during optimal staging surgery was performed in 10 patients who were diagnosed with primary epithelial ovarian cancers between April 2008 and February 2011. Cisplatin (70 mg/m(2) in 1 L normal saline solution) was administered in the abdominal cavity for 24 hours postoperatively and then adjuvant chemotherapy was started 2-4 weeks after surgery. Perioperative toxicity of the combined treatment was evaluated until the initiation of postoperative adjuvant chemotherapy. RESULTS: A total of 23 adverse events were observed in 9 of 10 patients (grade 1, 7; grade 2, 13; grade 3, 3; grade 4, 0). In descending order of frequency, adverse events affected the gastrointestinal system (n=14), hematologic system (n=6), pulmonary system (n=2), and genito-urinary system (n=1). The adverse events did not affect adjuvant systemic chemotherapy schedules. One patient experienced disease recurrence in the liver 16 months after surgery. The remaining 9 patients have been well controlled by chemotherapy and/or observation during the follow-up period of 4 to 39 months after surgery. CONCLUSION: Intraoperative IP chemotherapy with cisplatin during surgical procedures is considered feasible for the treatment of primary epithelial ovarian cancer. Further studies, including long-term, prospective and comparative trials, are needed to validate the efficacy of this combined therapy.

Prognostic value of the copper transporters, CTR1 and CTR2, in patients with ovarian carcinoma receiving platinum-based chemotherapy.

OBJECTIVE: CTR1 and CTR2 are copper transporters that have been associated with platinum sensitivity in several human cancers. We investigated the prognostic significance of CTR1 and CTR2 in women with ovarian carcinoma. MATERIALS AND METHODS: We evaluated the expression of CTR1 and CTR2 using real-time PCR in 40 women with ovarian carcinoma (IIb=2, IIIb=2, IIIc=30, IV=6). We compared the expression of CTR1 and CTR2 with participants' clinicopathological findings. RESULTS: We found lower expression of CTR1 and CTR2 mRNA in ovarian cancer cells against normal ovarian tissue with statistically significant differences (p=0.018 and 0.011, respectively). High CTR1 expression was a prognostic factor for improved survival after adjusting for age, tumor grade, stage, residual tumor, and CTR2 mRNA expression (HR, 0.35; 95% CI, 0.15-0.84). However, CTR2 expression did not exhibit any prognostic significance. Of the 20 women with elevated CTR1 expression, 17 (85%) were sensitive to platinum-based chemotherapy. Of the 7 women with low CTR1 expression and high CTR2 expression, 6 (85.7%) were resistant to platinum-based chemotherapy and had the shortest progression-free survival of all women in our study sample. CONCLUSION: In our sample of 40 women with ovarian carcinoma, high CTR1 expression was significantly associated with sensitivity to platinum-based chemotherapy and longer progression-free survival. Conversely, low CTR1 expression and high CTR2 expression were significantly associated with resistance to platinum-based chemotherapy and the shortest survival.

Phase II study of belotecan, a camptothecin analogue, in combination with carboplatin for the treatment of recurrent ovarian cancer.

BACKGROUND: Belotecan (CKD602; Camtobell, Chong Keun Dang Corp., Seoul, Korea) is a recently developed camptothecin derivative with antitumor properties. This phase II study was designed to evaluate the toxicity and efficacy of belotecan combined with carboplatin in patients with recurrent epithelial ovarian cancer (EOC). METHODS: Thirty-eight patients with recurrent EOC were treated with belotecan 0.3 mg/m(2) /day (days 1-5) and carboplatin AUC 5 (day 5) every 3 weeks for 6 cycles. The primary objective was to determine the response rate as defined by Response Evaluation Criteria in Solid Tumors and CA-125 response. Other end points included toxicities and progression-free survival (PFS). RESULTS: All 38 patients were assessed for toxicity, and 35 patients were assessed for response. The overall response rate was 57.1%; there were 7 complete responses (20.0%), 13 partial responses (37.1%), 6 patients with stable disease (17.1%), and 9 patients with progressive disease (25.7%). Grades 3 and 4 hematologic toxicities included neutropenia (28.8%), thrombocytopenia (19.8%), and anemia (14.4%), and there were 2 episodes of febrile neutropenia. Median PFS was 7 months, with a median follow-up of 12 months. CONCLUSIONS: The newly developed topoisomerase I inhibitor belotecan (CKD-602) combined with carboplatin is a well-tolerated regimen with activity in recurrent EOC. Further testing of this regimen is warranted to further characterize efficacy and indications for use.

Overexpression of Galectin-3 and its clinical significance in ovarian carcinoma.

BACKGROUND: Galectin-3 (Gal-3) is a ß-galactoside-binding lectin involved in regulating cell growth, angiogenesis, and tumor progression. We investigated the clinical significance of Gal-3 expression including its possible use as a prognostic marker or therapeutic target in epithelial ovarian carcinoma (EOC). METHODS: Gal-3 expression was evaluated by immunohistochemistry in 71 patients with 54 serous, 13 endometrioid, and 4 mucinous ovarian carcinomas. We assessed the correlation of Gal-3 expression with clinical characteristics including histology, optimal debulking, chemosensitivity, and survival. In vitro, Gal-3 was inhibited using siRNA to evaluate its role in cell growth and sensitivity to chemotherapeutic agents in ovarian carcinoma cell lines. RESULTS: Gal-3 protein, which was mainly cytoplasmic in location, was observed in a majority (63/71, 88.7%) of the EOCs but not in normal ovarian tissues (P < 0.001). High Gal-3 expression in EOCs correlated with shorter progression-free survival (PFS) of patients (P = 0.039; 43.1 and 49.5 months, respectively). Moreover, cotreatment with Gal-3 siRNA and paclitaxel showed an enhanced cytotoxic effect compared with control siRNA in SKOV3 cells. CONCLUSION: These findings suggest that Gal-3 expression can be a prognostic factor for PFS and may be involved in regulating the response to paclitaxel-based chemotherapy in the treatment of EOC.

Sequence-dependent hematologic side effects of topotecan and cisplatin in persistent or recurrent cervical cancer.

OBJECTIVE: This retrospective study evaluates the efficacy and toxicity of topotecan, followed by cisplatin, in patients with persistent or recurrent cervical cancer. METHODS: Twenty-four patients were included in the study. Ninety-two cycles of chemotherapy were administered during the study period. Topotecan (0.75 mg/m(2)) was administered as a 30-minute infusion on 3 consecutive days, and cisplatin was given intravenously at a dose of 50 mg/m(2) over 1h on day 3 of every third week. RESULTS: The median number of cycles administered was 3, with a range of 1-8 cycles per patient. There were 4 (16.7%) complete responses, 3 (12.5%) partial responses, and 5 (20.8%) stable disease. All of the patients with a complete response had received palliative radiation or surgery for pain or an isolated solitary recurrence prior to chemotherapy. There were no treatment delays of >7 days per cycle due to hematologic toxicity. There were 59 days of delay (average, 0.6 days per cycle) in 21 of 92 (22.8%) cycles and two episodes of dose reduction (cisplatin, 50% reduction) in 2 patients due to low creatinine clearance (30-60 mL/min). Overall, grade 3/4 anemia, thrombocytopenia, and neutropenia were experienced in 13.1%, 1.1%, and 18.5% of the courses, or 33.4%, 4.2%, and 45.8% of the patients, respectively. CONCLUSION: Combination chemotherapy, consisting of topotecan on days 1-3 and cisplatin on day 3, showed a relatively low rate of hematologic toxicity, as compared with the regimen of topotecan on days 1-3 and cisplatin on day 1, as used in previous studies.

Low dynamin 2 expression is associated with tumor invasion and metastasis in invasive squamous cell carcinoma of cervix.

Dynamin 2 is known as a protein involved in cell migration and endocytosis. We aimed to investigate the association between dynamin 2 expressions and tumor progression in early cervical carcinoma (IB1-IIA). Dynamin 2 expression was evaluated at protein level in thirty seven paraffin-embedded, formalin-fixed tissues including four normal cervix tissues and compared with pathologic risk factors for recurrence after surgery in thirty three patients with squamous cell carcinoma of the cervix. The expression of dynamin 2 was not different according to clinical stage and lympho-vascular space invasion. However, there were inverse correlations between dynamin 2 expression and the depth of invasion in cervix (p = 0.003) and lymph node (LN) metastasis (p = 0.001). To evaluate the mechanism of dynamin 2 in tumor invasion and metastasis, we performed an in vitro experiment with dynamin 2 siRNA using several cervical carcinoma cell lines such as HeLa, MS751 and SiHa cells. We found the inhibition of dynamin 2 using specific siRNA enhanced the expression of matrix metalloproteinase-2. These results suggested that dynamin 2 might be involved in preventing tumor invasion and LN metastasis, possibly in relation with extracellular matrix degradation, and may be a prognostic marker for these risk factors in early squamous cell carcinoma of the cervix.

Glucose as a prognostic factor in non-diabetic women with locally advanced cervical cancer (IIB-IVA).

OBJECTIVE: The aim of this study was to evaluate the association between pretreatment random plasma glucose levels and cancer prognosis in non-diabetic women with locally advanced cervical cancer treated with CCRT (concurrent chemoradiation) or RT (radiation therapy) only. METHODS: We investigated the non-fasting plasma glucose levels checked during the initial work up before treatment in 134 non-diabetic patients with locally advanced cervical cancer. Based on the survival time and the progression-free interval (PFI) recorded in the electronic medical records Cox proportional hazard regression models were used to estimate the hazard ratio (HR) for overall survival and PFI according to the various level of glucose and a cut-off level (<102 mg/dL and >or=102 mg/dL), adjusting for clinical covariates. RESULTS: A shorter overall survival and PFI was observed in the group with higher glucose levels (HR, 1.03; p=0.002, HR, 1.02; p=0.001, respectively) and more than 102 mg/dL, by univariate analyses (HR, 3.21; p=0.012, HR, 2.20; p=0.006, respectively). Multivariate analysis, adjusting for clinical FIGO stage, performance status, treatment type (CCRT vs. RT) and chemotherapeutic regimen types showed that patients with higher glucose levels or more than >or=102 mg/dL had shorter overall survival times (HR, 1.02; p=0.015, HR, 2.54; p=0.049, respectively) and PFI (HR, 1.02; p=0.003, HR, 1.88; p=0.031, respectively). CONCLUSION: This investigation provides evidence supporting the prognostic value of glucose levels in non-diabetic women with locally advanced cervical cancer treated with radiation therapy and/or concurrent chemotherapy; high glucose levels were associated with a greater risk for recurrence and mortality in these patients.