taxane and Uterine-Cervical-Neoplasms

Taxane/platinum (TP)-based combination chemotherapy is standard for the treatment of metastatic or recurrent cervical cancer. The aim of this study was to investigate the efficacy of postoperative TP therapy in early stage cervical cancer.. A retrospective review of patients with FIGO IB-IIB stage cervical cancer who were treated with radical hysterectomy and displayed surgical-pathological risk factors was performed. 122 patients were identified between 2003 and 2012. Survival was analyzed by Kaplan-Meier method and compared by the log-rank test. The Cox proportional hazards model was used to investigate predictors of survival.. The median follow-up period was 82.4 months. The postoperative adjuvant therapy was TP in 82 (67.2%) patients, other chemotherapies in 10 (8.2%), radiotherapy (RT) in 25 (20.5%), and no further therapy (NFT) in 5 (4.1%). Survival was analyzed using 4 subgroups according to the postoperative adjuvant therapy. The estimated 5-year overall survival was 95.1% in the TP group, 90.0% in the other chemotherapy group, 78.9% in the RT group, and 100% in the NFT group. No significant difference of survival was observed in the subgroups. However, when analyzing only patients who displayed high-risk factors, non-TP adjuvant therapy (including RT and other chemotherapies) was independently associated with shorter survival on multivariate analysis. In the TP group, multivariate analysis revealed that a positive surgical margin was a significant predictor of shorter survival.. Postoperative TP is effective in patients with surgically treated early stage cervical cancer. In these populations, a positive surgical margin could be associated with poor prognosis.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carcinoma, Squamous Cell; Combined Modality Therapy; Female; Humans; Hysterectomy; Lymphatic Metastasis; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Platinum; Postoperative Care; Prognosis; Retrospective Studies; Survival Rate; Taxoids; Uterine Cervical Neoplasms; Young Adult

Patients with cervical cancer recurrence after concurrent chemoradiotherapy (CCRT) who are not candidates for surgical resection or salvage radiotherapy have a dismal prognosis. The predictive factors for the effects of chemotherapy and prognostic factors in these patients were analyzed.. We collected data for patients with recurrent cervical cancer who were primarily treated with CCRT between 2000 and 2013. Among them, 57 patients treated with only systemic chemotherapy were analyzed for the overall survival (OS), the overall response rate (ORR), and prognostic factors.. The median age was 47 years. Inside the irradiated field recurrence occurred in 24, outside in 20 and both in 13 patients. Time to recurrence after the CCRT (i.e., therapy-free interval; TFI) were <6 months in 11, 6-12 months in 15, ≥12 months in 23 patients, and persistent disease in 8 patients. The median OS was 18 months and ORR was 15.7%. Those with a longer TFI showed a tendency for better ORR (p = 0.051) and those receiving a taxane-containing regimen showed significantly higher ORR (p = 0.0232). Multivariate analysis revealed a significant correlation between the median OS and TFI (HR = 4.688, 95% CI = 2.178-11.10, p < 0.0001) and chemotherapy response (HR = 20.08, 95% CI = 3.936-368.4, p < 0.0001). Furthermore, even in patients with stable disease, the median OS increased corresponding to the length of the TFI (p < 0.0001).. TFI has predictive value for response to chemotherapy and prognosis of patients with recurrent cervical cancer after definitive CCRT.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Chemoradiotherapy; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Retrospective Studies; Salvage Therapy; Taxoids; Treatment Outcome; Uterine Cervical Neoplasms

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

The inhibitory effect of 13 taxanes isolated from the Chinese yew (Taxus chinensis var. mairei) on the proliferation of human cervical cancer HeLa cells were examined using an MTT assay. Four compounds having a hydrophobic cinnamate side chain showed antiproliferative activity, which may be due to increased cell permeability.

Topics: Antineoplastic Agents; Apoptosis; Bridged-Ring Compounds; Cell Proliferation; Diterpenes; Female; HeLa Cells; Humans; Hydrophobic and Hydrophilic Interactions; Taxoids; Taxus; Uterine Cervical Neoplasms

An effective salvage chemotherapy for advanced and recurrent non-squamous carcinoma of the uterine cervix has not yet been established. The aim of the present study was to analyze the safety and efficacy of a combination chemotherapy for this disease using taxane, anthracycline, and platinum.. This was a retrospective analysis of advanced and recurrent non-squamous cervical cancers treated at the Osaka University Hospital and the Osaka Medical Center for Cancer and Cardiovascular Diseases during a 10 year study period from 2000 to 2009. Single agent chemotherapies and combination chemotherapies for advanced and recurrent cervical cancer cases of non-squamous histology which were reported in the English literature were also reviewed.. Salvage chemotherapy, using taxane, anthracycline and platinum, was performed for 5 advanced and 14 recurrent cases. Prior to the salvage chemotherapy, 15 (79%) of the 19 patients had already received either radiation or chemotherapy. A complete or partial tumor response was achieved in 8 (42%) of the 19 cases. The response rate for recurrent disease in a previously irradiated field was 40%. The median progression-free survival (PFS) and overall survival (OS) were 8 months (1-108) and 13 months (5-108), respectively. Grade 4 and febrile grade 3 neutropenia was observed in 6 cases (32%), but there was no case in which salvage chemotherapy had to be cancelled due to toxicity. According to previous reports, the cumulative response rate of combination chemotherapy (35%) was significantly higher than that of single agent chemotherapy (17%) (p<0.001). OS tended to be longer in the combination chemotherapy cases (8.7 months to 18 months) than that of single agent chemotherapy cases (7.3+ months to 9.1+ months).. Combination chemotherapy of taxane, anthracycline, and platinum was found to have a survival benefit for advanced and recurrent cervical cancer patients of non-squamous carcinoma histology, with a tolerable toxicity.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carboplatin; Carcinoma; Cisplatin; Female; Fever; Follow-Up Studies; Humans; Medical Records; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Retrospective Studies; Salvage Therapy; Survival Analysis; Taxoids; Uterine Cervical Neoplasms; Young Adult

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

Using a model of human cervical cancer (ME-180 cells), the anti-tumour activity of paclitaxel was compared to that of docetaxel and IDN5109, a newly developed taxane. The growth inhibition effect of taxanes was assessed after 3 days of exposure. DNA analysis, the taxane-dependent modulation of the expression of the alpha and beta subunits of tubulin and DNA fragmentation were assessed by flow cytometry. The presence of apoptosis was confirmed by morphological analysis using a laser scan cytometer. For the evaluation of "in vivo" anti-tumour activity, taxanes were administered to nude mice intravenously once daily, according to a q3/4d x 4 schedule. Docetaxel, IDN5109 and paclitaxel obtained "in vitro" IC(50) values of 0.86, 1.4 and 2.4 nM, respectively. DNA analysis demonstrated a transient block at the G(2)/M phase of the cell cycle only after 12 h of culture in the presence of taxanes and an increase of nuclear fragmentation suggestive for apoptosis after additional 12 and 60 h of exposure. Morphological analysis confirmed the presence of apoptosis. Taxanes induced a down-modulation of the alpha subunit of tubulin in the G(0/1) phase of the cell cycle, and an overexpression of the beta subunit in the G(2)/M phase. A strong anti-tumour activity was obtained "in vivo" for nude mice xenografted using ME-180 cells (T/C=0% for all drugs). These data indicate that the three taxanes are strongly active both "in vitro" and "in vivo" toward ME-180 cells. Clinical studies are now needed to ascertain if the higher anti-tumour activity observed "in vitro" using docetaxel and IDN5109 yields a better clinical response in advanced cervical carcinoma with respect to paclitaxel.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Bridged-Ring Compounds; Cell Cycle; DNA, Neoplasm; Docetaxel; Drug Screening Assays, Antitumor; Female; Flow Cytometry; Humans; Mice; Mice, Nude; Paclitaxel; Taxoids; Transplantation, Heterologous; Tubulin; Tumor Cells, Cultured; Uterine Cervical Neoplasms