Retrospective comparative study of irinotecan and pegylated liposomal doxorubicin for platinum-resistant or -refractory epithelial ovarian and primary peritoneal carcinoma.

PURPOSE: This study was conducted to retrospectively compare the efficacy and safety of irinotecan (CPT-11) and pegylated liposomal doxorubicin (PLD) in patients with platinum-resistant or -refractory recurrent epithelial ovarian and primary peritoneal carcinoma. METHODS: Nineteen patients who received CPT-11 and eleven patients who received PLD were enrolled. CPT-11 was intravenously administered at a starting dose of 60-100 mg/m(2) on day 1, 8, and 15 every 28 days, and PLD was administered at a starting dose of 40-50 mg/m(2) on day 1 every 28 days. Primary outcomes were overall response rate (complete response [CR] + partial response [PR]), disease control rate (CR + PR + stable disease), and progression-free survival (PFS) in each group. Clinical response was evaluated every two or three cycles using the Response Evaluation Criteria in Solid Tumors criteria; CA125 analysis was not performed. RESULTS: The overall response rate was 21.1 % (PR, four cases) and 0 % (p = 0.10) in the CPT-11 and PLD groups, respectively, and the disease control rate was 73.7 and 45.5 % (p = 0.12), respectively. Median PFS was 25.3 (range 5.4-69.9) weeks and 12.7 (range 4.0-43.1) weeks in the CPT-11 and PLD groups, respectively; however, this difference was not statistically significant (p = 0.064). Major adverse events in the CPT-11 group were neutropenia, nausea, and diarrhea, whereas those in the PLD group included thrombocytopenia, anemia, stomatitis, and hand-foot syndrome. CONCLUSIONS: This retrospective study demonstrated comparable efficacy outcomes for CPT-11 and PLD. The overall response rate, disease control rate, and median PFS were more favorable in the CPT-11 group compared to the PLD group, although the difference was not significant. The adverse event profiles were different between groups. These results suggest that CPT-11 might be a feasible choice as single-agent salvage chemotherapy for platinum-resistant or -refractory recurrent epithelial ovarian and primary peritoneal carcinoma beside established regimen like PLD.

Human epidermal growth factor receptor-2 overexpression and amplification in metastatic and recurrent high grade or type 2 endometrial carcinomas.

INTRODUCTION: Human epidermal growth factor receptor (HER)-2 overexpression or gene amplification is more common in high-grade or type 2 endometrial carcinomas. We assessed the discordance of HER-2 expression between primary and metastatic or recurrent endometrial carcinomas. MATERIALS AND METHODS: Thirty-six primary, along with 14 metastatic and five recurrent tumors (matched to primaries), pathologically confirmed as high-grade or type 2 endometrial carcinomas, were submitted for immunohistochemistry (IHC) for HER-2. Fluorescence in situ hybridization was performed when the tumors showed HER-2 overexpression (≥2+ IHC score). The results of the IHC and fluorescence in situ hybridization assays were compared between the primary and metastatic or recurrent tumors. The relationships between HER-2 expression and clinicopathological factors or prognosis were investigated. RESULTS: HER-2 overexpression and HER-2 amplification (a ratio of HER-2 copies to chromosome 17 [CEP17] copies ≥2.2) were detected in 33.3% (twelve of 36 patients) and 5.6% (two of 36 patients) of primary tumors, respectively. HER-2 overexpression was not associated with clinicopathological factors or prognosis. In 19 tumor specimens obtained from metastatic or recurrent tumors, HER-2 overexpression and HER-2 amplification were detected in 57.9% (eleven patients) and 15.8% (three patients), respectively. HER-2 overexpression tended to predict a worse prognosis. CONCLUSION: HER-2 expression in metastatic or recurrent tumors was more frequent than in matched primary high-grade or type 2 endometrial carcinomas. Trastuzumab in combination with cytotoxic chemotherapy may represent an alternative therapeutic option for these tumors.

The relationship between ERCC1 expression and clinical outcome in patients with FIGO stage I to stage II uterine cervical adenocarcinoma.

OBJECTIVE: Several studies have suggested that excision repair cross-complementation group 1 (ERCC1), a protein involved in nucleotide excision repair, is associated with resistance to platinum agent-based chemotherapy or chemoradiotherapy with platinum agents in various types of cancer. Herein we evaluated ERCC1 protein expression in uterine cervical adenocarcinoma and the relationship between this expression, clinicopathological factors, and clinical outcome, particularly in patients receiving adjuvant cisplatin-based chemotherapy or chemoradiotherapy with cisplatin. METHODS: Thirty-six patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB to stage IIB cervical adenocarcinoma who underwent radical hysterectomy were evaluated. Excision repair cross-complementation group 1 protein expression was examined by immunohistochemistry in tumor tissues. The relationship between ERCC1 expression levels and clinicopathological factors (age, FIGO stage, histological grade, tumor size, vascular invasion, cervical stromal invasion, and lymph node metastases) and prognosis was evaluated. RESULTS: No significant differences between ERCC1 expression levels and clinicopathological factors were observed. The patients in the ERCC1 high-expression group (n = 7) experienced significantly worse disease-free survival than the patients in the ERCC1 low-expression group (n = 29; P = 0.005). Among the 25 patients who received cisplatin-based chemotherapy or chemoradiotherapy with cisplatin, those with high ERCC1 expression (n = 5) also experienced significantly worse disease-free survival than those with low ERCC1 expression (n = 20; P = 0.002). Moreover, univariate and multivariate analyses revealed that high ERCC1 expression was an independent prognostic factor in patients receiving cisplatin-based chemotherapy or chemoradiotherapy with cisplatin. CONCLUSIONS: This is the first analysis of the association between ERCC1 expression and clinical outcomes in patients with uterine cervical adenocarcinoma. High ERCC1 protein expression was revealed to be associated with worse disease-free survival in the patients who received adjuvant cisplatin-based chemotherapy or chemoradiotherapy with cisplatin and was shown to be an independent prognostic factor. Further evaluation with a larger number of patients is required to confirm these preliminary observations.

[Treatment outcomes for advanced ovarian cancers with peritoneal dissemination].

PURPOSE: The prognosis of advanced ovarian cancer primarily depends on maximal surgical debulking and chemosensitivity of the tumor. Neo-adjuvant chemotherapy(NAC), maintenance chemotherapy, and interval debulking surgery(IDS)are sometimes used to improve the prognosis of advanced ovarian cancer patients. In this study, we evaluated the outcomes of these therapeutic options in the treatment of FIGO stage III and IV ovarian cancers with intraperitoneal dissemination. METHODS: Fifty patients with FIGO stage IIIc and IV ovarian cancer were evaluated. Progression-free survival(PFS)and overall survival(OS)were compared between different patient groups, including patients who underwent optimal surgery versus suboptimal surgery, patients who received NAC versus those who did not, patients who received 6 cycles of postoperative adjuvant chemotherapy versus those who received more than 7 cycles, and patients who underwent IDS versus those who did not. RESULTS: 1 ) The 5- and 10-year OS rates were 52% and 21%, respectively. 2 ) Patients in the optimal surgery group experienced significantly longer PFS than patients in the suboptimal surgery group(p=0. 04). 3) Although NAC increased the possible rate of optimal surgery from 31. 2% to 66. 7%, no significant differences in PFS or OS were observed between patients who did and did not receive NAC. 4 ) Patients who underwent more than 7 cycles of adjuvant chemotherapy after suboptimal surgery experienced significantly longer OS(p=0. 001)and a tendency toward longer PFS(p=0. 07)compared to patients who received 6 cycles of adjuvant chemotherapy. 5 ) Patients who achieved a complete response(CR)following adjuvant chemotherapy after suboptimal surgery experienced significantly longer PFS(p=0. 001)and OS(p=0. 001) compared to patients who did not obtain CR. Moreover, patients who underwent IDS and who did not obtain a CR after adjuvant chemotherapy tended to experience longer PFS than patients who did not undergo IDS(p=0. 07). CONCLUSIONS: The results of this study are essentially compatible with those of recent randomized controlled trials(RCTs) evaluating NAC, maintenance chemotherapy, and IDS in advanced ovarian cancer. We hope to obtain additional RCT results that will allow improvement of the prognosis of advanced ovarian cancer patients.

A case of primary alveolar soft part sarcoma of the uterine cervix and a review of the literature.

Alveolar soft part sarcoma (ASPS) that originates from the uterine cervix is extremely rare, with only thirteen cases reported. The participation of the ASPL-TFE3 chimeric gene, translocation (X; 17) (p11; q25), has been demonstrated in ASPS. Here, we report a case of cervical ASPS, along with a review of the literature. The patient, a 56-year-old woman, was referred for a 70 × 80 mm cervical tumor. She underwent a hysterectomy and bilateral salpingo-oophorectomy, and remained disease free for 66 months without adjuvant therapy. Pathological examination revealed features consistent with ASPS. In addition, the present case demonstrated strong positive nuclear staining for TFE3, and ASPL-TFE3 fusion gene type 1 was detected by RT-PCR. In a review of fourteen cases of this tumor (including the present case), the immunohistochemical expression patterns of myogenic or neuroendocrine markers were somewhat varied among cases. In all cases except for the present case, the patients were under 40 years of age, and the tumor sizes were under 5 cm. The prognosis of ASPS in the cervix was considerably better than that of ASPS in soft tissues. Complete resection with adequate margins is thought to be important, although the appropriate surgical method, including lymph node dissection, is uncertain. The role of chemotherapy or radiotherapy as adjuvant therapy has not been defined. Cervical ASPS is extremely rare, making case series the most viable option for understanding their natural history and for developing a treatment strategy, including an optimal surgical procedure and adjuvant therapy.

Effects of a selective COX-2 inhibitor in patients with uterine endometrial cancers.

PURPOSE: COX-2 is highly expressed in endometrial cancers, suggesting that a selective COX-2 inhibitor could be valuable for treating endometrial cancers that overexpress COX-2. In this study, we investigated the anti-tumor effects of the selective COX-2 inhibitor etodolac on endometrial cancer patients. METHODS: Etodolac (400 mg, bid, for 2 weeks) was administered preoperatively to 21 endometrial cancer patients who had provided informed consent. Using pre-treatment biopsies and post-treatment surgical specimens, the expression levels of COX-2, Ki-67, p53, p21, p27, and cyclin D1 were evaluated by immunohistochemistry and the apoptotic index (AI) was determined by TUNEL staining. Preoperative biopsies and surgical specimens from 32 patients with endometrial cancer not treated with etodolac served as controls. RESULTS: Surgical specimens from COX-2 positive endometrial cancer patients treated with etodolac had significantly reduced expression levels of COX-2, Ki-67, p53, p21, p27, and cyclin D1 as determined by immunohistochemistry, while AI was not affected. These markers were unchanged for COX-2 negative endometrial cancer patients treated with etodolac and the control group. CONCLUSIONS: The selective COX-2 inhibitor etodolac showed anti-proliferative effects by suppressing COX-2 and cell-cycle regulator protein expression in patients with endometrial cancer positive for COX-2 expression. This study demonstrates that a selective COX-2 inhibitor is a potentially beneficial treatment for COX-2 positive endometrial cancers.

A case of primary uterine cervical neuroendocrine tumor with meningeal carcinomatosis confirmed by diagnostic imaging and autopsy.

Primary uterine cervical neuroendocrine tumors are rare, but affect relatively young women and the prognosis is poor despite multidisciplinary treatment. The incidence of meningeal carcinomatosis arising from malignant tumors of the uterine cervix is extremely low, only two patients with meningeal carcinomatosis arising from a uterine cervical neuroendocrine tumor have been reported in the English literature. Moreover, there have been no reports in which this was confirmed at autopsy. We encountered a pregnant woman aged 33 years who was diagnosed as having atypical carcinoid of the uterine cervix after radical surgery. Despite multidrug chemotherapy (paclitaxel + etoposide + cisplatin and irinotecan + carboplatin), the patient developed multiple organ metastases. Although there was no metastasis to the brain parenchyma or the spinal cord parenchyma, the patient also developed meningeal carcinomatosis. Whole-brain radiation therapy was performed, but was ineffective. The patient died at 19 months after her initial operation and 10 days after diagnosis of meningeal carcinomatosis. The presence of meningeal carcinomatosis was confirmed at autopsy.

Expression of podoplanin in epithelial ovarian carcinomas and its potential as a marker for clear cell adenocarcinoma.

Podoplanin is a 43-kd mucin-type transmembrane glycoprotein that is a candidate marker for the pathologic diagnosis of mesothelioma and lymphatic endothelial cells and lymphangiogenesis. The aim of this study was to investigate podoplanin expression in epithelial ovarian carcinomas. Immunohistochemistry was performed on the paraffin-embedded tissues from 78 patients with epithelial ovarian carcinomas consisting of serous adenocarcinoma (SA), endometrioid adenocarcinoma (EM), mucinous adenocarcinoma (MA), and clear cell adenocarcinoma (CCC) cases. Only 36.8% (7/19) of SA, 33.3% (6/18) of EM, and 15.8% (3/19) of MA cases were positive for podoplanin expression, whereas 54.5% (12/22) of CCC samples were positive. Immunohistochemical scores (mean+/-SD) were 1.2+/-1.5, 1.9+/-2.6, 0.8+/-1.6 and, 3.6+/-4.0 in SA, EM, MA, and CCC, respectively. Podoplanin expression was significantly stronger in CCC than in other histologic types. However, no significant correlation was observed between its expression and FIGO stage, the presence of endometriosis, lymph node metastasis, or recurrence. There was also no correlation between podoplanin expression and overall survival. We confirmed the expression of podoplanin in epithelial ovarian carcinomas, particularly in CCC. Podoplanin might have utility as a marker for CCC in pathologic diagnosis. Further investigation is needed to clarify the relationship between podoplanin expression and the biologic characteristics of CCC.