belotecan and Uterine-Cervical-Neoplasms

The Phase II trial was conducted to evaluate the efficacy and toxicity of belotecan (CKD 602), a topoisomerase I inhibitor, in persistent or recurrent carcinoma of the cervix.. Belotecan was administrated at 0.5 mg/m(2)/day for 5 consecutive days every 3-week cycle in patients with recurrent or progressive cervical carcinoma who were unsuitable candidates for curative treatment with surgery or radiotherapy.. At the first stage of trial, a total of 16 patients were entered in the study. A median of three cycles were administrated per patient with a range of one to seven cycles. Fourteen of 16 patients (87.5%) had received radiotherapy or chemotherapy prior to the study. The most frequently severe adverse events were anemia and neutropenia. More than Grade 3 anemia and neutropenia were seen in 10 cycles (23.8%) and 6 cycles (14.3%) of 42 cycles, respectively. The incidence of non-hematologic toxicity was minimal. One patient died of treatment-related toxicities. There was no complete or partial response to belotecan. The median overall survival was 12.38 months (95% confidence interval, 9.71-15.04).. Belotecan was not active in the treatment of recurrent or progressive cervical cancer as a single agent. ClinicalTrials.gov identifier: NCT00430144.

Topics: Adult; Aged; Antineoplastic Agents; Blood Cells; Camptothecin; Digestive System; Disease Progression; Drug Administration Schedule; Early Termination of Clinical Trials; Female; Humans; Incidence; Middle Aged; Neoplasm Recurrence, Local; Nervous System; Respiratory System; Skin; Topoisomerase I Inhibitors; Treatment Failure; Uterine Cervical Neoplasms

Cervical cancer is the third most common gynecological malignancy. Conventional treatment options are known to be ineffective for the majority of patients with advanced or recurrent cervical cancer. Therefore, novel therapeutic agents for cervical cancer are necessary. In this study, the effects of CKD-602 in cervical cancer were investigated.. Three established human, immortalized, cervical cancer cell lines (CaSki, HeLa and SiHa) were used in this study. Following treatment with CKD-602, apoptosis was quantified using fluorescein isothiocyanate Annexin V-FITC and propidium iodide (PI) detection kit and cell cycle analysis was analyzed using fluorescence activated cell sorting (FACS). Transwell chambers were used for invasion assays. Western blot assay was performed to analyze proteomics. CaSki cells were subcutaneously injected into BALB/c-nude mice and cervical cancer xenograft model was established to elucidate the antitumor effect of CKD-602 in vivo.. Treatment with CKD-602 induced apoptosis and increased expression of the enzyme PARP, cleaved PARP, and BAX. In addition, expression of phosphorylated p53 increased. Cell cycle arrest at G2/M phase and inhibition of invasion were detected after treatment with CKD-602. A significant decrease in cervical cancer tumor volume was observed in this in vivo model, following treatment with CKD-602.. This is the first report of CKD-602 having an antitumor effect in cervical cancer in both an in vitro and in vivo models. The results of this study indicate that CKD-602 may be a novel potential drug, targeting cervical cancer, providing new opportunities in the development of new therapeutic strategies.

Topics: Animals; Apoptosis; Camptothecin; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Movement; Female; Flow Cytometry; G2 Phase Cell Cycle Checkpoints; HeLa Cells; Humans; Mice, Inbred BALB C; Mice, Nude; Topoisomerase I Inhibitors; Uterine Cervical Neoplasms; Xenograft Model Antitumor Assays