taxane and Adenocarcinoma--Mucinous

We conducted this study to evaluate the efficacy and safety of adjuvant chemotherapy using taxane plus carboplatin (CBDCA) for high-risk stage IB-IIB patients with uterine cervical non-squamous cell carcinoma after radical hysterectomy.. Thirty-seven patients were eligible. Pelvic lymph node involvement and/or parametrial invasion were defined as high-risk factors. The patients were treated with 6 cycles of paclitaxel (PTX, 175 mg/m(2)) or docetaxel (DTX, 60 mg/m(2)) followed by CBDCA (area under the curve, 6) every 3 weeks. The primary end point was 2-year progression-free survival (PFS) rate, and the secondary end point was the assessment of adverse events.. Twenty-two patients received PTX/CBDCA (TC) chemotherapy, and the remaining 15 patients underwent DTX/CBDCA (DC) chemotherapy. The 2-year PFS rate was 62.1% (95% confidence interval, 44.6%-75.5%). Patients receiving DC chemotherapy showed a better 2-year PFS rate compared to those with TC chemotherapy, but the difference was not statistically significant (80.0% vs 50.0%, P = 0.1400). The most common grade 3/4 adverse events were hematologic toxicities, which were generally well tolerable. Nonhematologic toxicity was generally mild.. Taxane and CBDCA combination chemotherapy, especially DC chemotherapy, may be one of the useful adjuvant treatments for high-risk stage IB-IIB patients with uterine cervical non-squamous cell carcinoma after radical hysterectomy.

Topics: Adenocarcinoma, Clear Cell; Adenocarcinoma, Mucinous; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carboplatin; Carcinoma, Adenosquamous; Chemotherapy, Adjuvant; Endometrial Neoplasms; Feasibility Studies; Female; Follow-Up Studies; Humans; Hysterectomy; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Survival Rate; Taxoids; Uterine Cervical Neoplasms

A relationship between inactivation of mitotic checkpoint genes and sensitivity of cancer cells to anticancer agents has been reported. We investigated the effect of epigenetic inactivation by aberrant hypermethylation of the mitotic checkpoint gene CHFR (checkpoint with forkhead and ring finger) on the sensitivity of cervical cancer cells to taxanes. Methylation-specific PCR (MSP) of cervical smears showed aberrant methylation of CHFR in 12.3% (2/14) of adenocarcinoma specimens. In contrast, aberrant DNA methylation was not detected in normal cervical cells or squamous cell carcinoma cells. Aberrant methylation of CHFR was also analyzed in 6 human cervical carcinoma-derived cell lines and was observed in SKG-IIIb and HeLa cells. These cell lines showed high sensitivity to taxanes, but became taxane-resistant upon treatment with 5-azacytidine. Furthermore, suppression of CHFR expression in siRNA-transfected SKG-IIIa cells caused increased sensitivity to taxanes. In conclusion, aberrant methylation of the CHFR gene may be useful as a molecular marker for selection of therapy for patients with cervical adenocarcinoma with a poor prognosis, and may also suggest a new therapeutic strategy of targeting CHFR in cervical cancer. To our knowledge, this study is the first to examine epigenetic inactivation by aberrant hypermethylation of CHFR in cervical cancer.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Antimetabolites, Antineoplastic; Antineoplastic Agents; Azacitidine; Bridged-Ring Compounds; Carcinoma, Squamous Cell; Cell Cycle Proteins; DNA Methylation; DNA, Neoplasm; Drug Tolerance; Epigenesis, Genetic; Female; Gene Expression Regulation, Neoplastic; Gene Silencing; Humans; Neoplasm Proteins; Poly-ADP-Ribose Binding Proteins; Promoter Regions, Genetic; RNA, Small Interfering; Taxoids; Tumor Cells, Cultured; Ubiquitin-Protein Ligases; Uterine Cervical Neoplasms

The objective of the present study was to compare recurrence-free survival (RFS) in early stages (FIGO stages I-II) of epithelial ovarian cancer after adjuvant chemotherapy with carboplatin and a taxane (113 patients) and with carboplatin alone (27 patients). The distribution of clinical and pathological prognostic factors as well as type of primary surgery were comparable in the two groups. Recurrence rate was 21% and RFS was 79% in the series of patients treated with taxane-based chemotherapy and 19% and 81%, respectively, in the series of patients who received single drug carboplatin. Thus, no significant differences were recorded. The major toxicities in the present study were myelosuppression (46%) and neuro-toxicity (26%). Neuro-toxicity was more frequently (P=0.007) recorded and of higher grade (P=0.011) for patients in the carboplatin-taxane series compared with patients in the carboplatin series. RFS for patients in FIGO-stage I was 85% and for patients in FIGO-stage II only 47%. In a multivariate logistic regression analysis of predictive factors for tumor recurrence in the complete series (n=140) the FIGO stage was the only independent and significant (P=0.0006) predictive factor with an odds ratio of 6.4 (95% CI: 2.2-18.9) for stage II versus IA-C. Age, tumor grade and type of adjuvant chemotherapy (+/- taxane) were not significant predictive factors. In the present study, although based on a limited number of patients, we could not find any improvement in recurrence rate or recurrence-free survival for patients treated with a carboplatin-taxane combination regimen compared with patients treated with carboplatin monotherapy. The spectrum of side effects was also in favor of the monotherapy regimen. Further, larger randomized studies are needed to give a final and fully conclusive answer to this question.

Topics: Adenocarcinoma, Clear Cell; Adenocarcinoma, Mucinous; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carboplatin; Carcinoma, Endometrioid; Chemotherapy, Adjuvant; Cystadenocarcinoma, Serous; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Prognosis; Survival Rate; Taxoids