Effectiveness of third-line chemotherapy in recurrent ovarian cancer patients.

OBJECTIVE: Despite recent advances in the treatment of recurrent ovarian cancer, little evidence exists describing the benefit of third- line chemotherapy. The present authors previously reported that the treatment-free interval (TFI) after second-line chemotherapy may predict a survival benefit of third-line chemotherapy, however the length of TFI was uncertain due to limited cases. In this study, the authors evaluated the length of TFI, which is correlated with the effectiveness of third-line chemotherapy and a prognostic factor of third-line chemotherapy. MATERIALS AND METHODS: The authors reviewed the medical records of 85 women with recurrent ovarian cancer who received third-line chemotherapy after a paclitaxel/carboplatin (PC) regimen as first-line chemotherapy. RESULTS: The response rate [complete response (CR) + partial response (PR)] and clinical benefit rate [(CBR): CR + PR + stable disease (SD)] during the TFI after second-line chemotherapy for 0-3 months, 3-6 months, and 6-12 months and ≥ 12 months were 9.8%, 0%, 0%, 43.8% and 15.7%, 50%, 66.7%, and 93.8%, respectively. The median overall survival (OS) from the onset of third-line chemotherapy was longer for TFI ≥ 3 months than for TFI 0-3 months (795 days vs. 281 days, p < 0.001). Finally, according to univariate (HR = 0.256; p < 0.001) and multivariate (HR = 0.264; p < 0.001) analyses, TFI was the independent significant prognostic factor for OS. CONCLUSIONS: TFI less than three months after second-line chemotherapy may predict little survival benefit of third-line chemotherapy.

Retrospective study comparing irinotecan and pegylated liposomal doxorubicin in treatment of recurrent platinum-refractory/resistant epithelial ovarian cancer.

PURPOSE: The standard regimen for platinum-resistant/refractory recurrent epithelial ovarian cancer (EOC) remains to be determined. In this study, we retrospectively compared the effect of irinotecan (CPT-11) and pegylated liposomal doxorubicin (PLD) in the treatment of platinum-resistant recurrent EOC. METHODS: Thirty patients who received salvage chemotherapy with CPT-11 or PLD were included in the study. CPT-11 (100 mg/m2) was administered intravenously on days 1, 8 and 15 every four weeks. PLD (50 mg/m2) was administered on day 1 every four weeks. Treatment was repeated, provided that no disease progression or intolerable toxicity occurred. RESULTS: Response rate in the CPT-11 group and PLD group showed no difference at 26.7% (p = 0.66) in both, while non-PD rate was 73.3% vs. 33.3% (p < 0.05), respectively. Progression-free survival after CPT-11 treatment and PLD treatment was 28.4 weeks and 16.8 weeks (p = 0.07), respectively. Hand-foot syndrome and mucositis were more common in the PLD group than in the CPT-11 group (p < 0.05). CONCLUSIONS: The results indicate that CPT-11 is a promising drug for the treatment of platinum-resistant recurrent EOC.

Expression of hypoxia-inducible 2 (HIG2) protein in uterine cancer.

For both cervical cancer (UCC) and endometrial cancer (EMC) there are no effective prognostic markers. In this study, we evaluated HIG2 protein expression in 332 uterine cancers (186 UCCs and 146 EMCs) and examined the relationship between HIG2 protein expression and clinical factors, including prognosis. Totally, HIG2 expression was detected in 58% of UCC and 66% of EMC. However, there was no significant relationship between HIG2 expression and age, clinical stage and histology in either UCC or EMC. In addition, HIG2 protein expression was not related to prognosis of UCC or EMC. The positivity rate of HIG2 protein was 56% and 61% in early-stage UCC and EMC, respectively and 67% in non-squamous cell carcinoma of UCC. The positivity rate of HIG2 protein was high even in early-stage UCC and EMC

The chemosensitivity of nodal metastases in recurrent epithelial ovarian cancer.

PURPOSE: In this study, we compared second-line chemotherapy effects of nodal metastases with other metastases sites. METHODS: The medical records of 44 women with recurrent ovarian cancer who received second-line chemotherapy were retrospectively reviewed. RESULTS: Median age at the time of second-line chemotherapy was 55 years (range: 31-74). Recurrent sites were as follows: 29 patients had a solitary site (abdominal cavity: 8; lymph node: 3; pelvic cavity: 10; liver: 4; lung: 4) and 15 patients had multiple sites In total, the response rate was 30% (CR: 8, PR: 5). The response rate in sensitive cases was higher than in refractory/resistant cases (50% vs 5% p = 0.002). However, age, chemotherapy regimen, histologic type and number of diseases were not related with chemotherapy effect. In all diseases, response rate tended to be higher in lymph node disease than in the others (44% vs 27%). In both sensitive and refractory/resistant cases, response rate tended to be higher in lymph node disease. CONCLUSION: The response rate for lymph node diseases tended to be relatively high. Further study analyzing survival will be required to conclude the chemotherapy effect.

Effects of third-line chemotherapy for women with recurrent ovarian cancer who received platinum/taxane regimens as first-line chemotherapy.

PURPOSE: At present, it remains unclear whether the third-line chemotherapy has clinical benefit. In this study, we retrospectively evaluated the effect of third-line chemotherapy. METHODS: We reviewed the medical records of 40 women with recurrent epithelial ovarian cancer (EOC) who received third-line chemotherapy after platinum/taxan regimens as first line chemotherapy. RESULTS: In the first recurrence, 23 cases were platinum-sensitive and 17 cases were platinum-resistant. The cases for which the treatment-free interval from second-line chemotherapy (TFI) was a 3 months had a higher non-PD rate than those with TFI < 3 months (86% vs 33%, p = 0.002). In addition, the median overall survival (OS) was longer for TFI > or = 3 months than for TFI < 3 months (1195 days vs 235 days, p = 0.004). Finally, TFI was an independent significant prognostic factor by univariate (HR 3.28, p = 0.006) and multivariate (HR 3.21, p = 0.018) proportional hazard tests. CONCLUSION: TFI from second-line chemotherapy may predict a survival benefit of third-line chemotherapy.

Can ABCF2 protein expression predict the prognosis of uterine cancer?

Uterine cervical and endometrial cancers are common malignant solid neoplasms for which there are no useful prognostic markers. In this study, we evaluate the relationship between ATP-binding cassette superfamily F2 (ABCF2) expression and clinical factors including clinical stage, histologic type, grade and prognosis in uterine cervical and endometrial cancer. Two hundred and sixty seven cervical and 103 endometrial cancers were studied. ATP-binding cassette superfamily F2 cytoplasmic expression was detected by immunohistochemical staining and scored as positive or negative. Among cervical cancer cases, 149 (55.8%) expressed ABCF2. The overall survival was longer in ABCF2-negative than ABCF2-positive cases (P=0.0069). Statistically significant prognostic factors for survival were ABCF2 positivity (risk ratio (rr)=1.437), old age (rr=1.550) and advanced stage (rr=2.577). ATP-binding cassette superfamily F2 positivity was an independent prognostic factor by multivariate proportional hazard test (P=0.0002). Among endometrial cancer cases, 72 (69.9%) were cytoplasmic ABCF2 positive. However, there was no significant relationship between ABCF2 expression and age, clinical stage, histologic type, histologic grade, oestrogen receptor status or prognosis. ATP-binding cassette superfamily F2 expression may be a useful prognostic marker in cervical but not endometrial cancer. The role of ABCF2 protein may differ depending on the type of cancer.

Screening system for urease inhibitors using 13C-NMR.

Urease inhibitors are candidate drugs to treat infection with the human pathogen, Helicobacter pylori, which produces a potent urease [urea amidohydrolase; EC 3.5.1.5]. We developed a screening system based on 13C-NMR measurement of the time course of decrease in the signal of 13C-urea in the presence of urease. The effect on urease activity of known inhibitors, hydroxamic acids, L-ascorbic acid, 2,2'-dipyridyl disulfide and ninhydrin, was speedily and conveniently measured by this method.