Belotecan and Cisplatin Combination Chemotherapy for Previously Untreated Extensive-Disease Small Cell Lung Cancer

PURPOSE: Belotecan (Camtobell(R); Chong Keun Dang Co., Seoul, Korea) is a new camptothecin analog that inhibits topoisomerase I. We evaluated the efficacy and toxicity of belotecan combined with cisplatin in patients with previously untreated extensive-disease small cell lung cancer (ED-SCLC) and who were without evidence of brain metastases. MATERIALS AND METHODS: Twenty patients with previously untreated ED-SCLC were treated with belotecan (0.5 mg/m2/day) on days 1~4 and with cisplatin (60 mg/m2/day) on day 1 of a 3-week cycle. RESULTS: Of the 19 assessable patients, 16 had an objective tumor response, including two complete responses, for an overall response rate of 84.2%. Toxicity was evaluated in all 20 patients who received a total of 106 cycles (median cycles/patient, 5.5; range, 1~9). The major grade 3/4 hematologic toxicities were neutropenia (67.9% of cycles), anemia (19.8% of cycles) and thrombocytopenia (33.9% of cycles). No grade 3/4 non-hematologic toxicities were observed. No treatment-related deaths occurred. The median progression-free and overall survivals were 7.06 months (95% confidence interval [CI], 3.98~10.14 months) and 9.96 months (95% CI, 6.12~13.80 months), respectively. CONCLUSION: Combination chemotherapy with belotecan plus cisplatin is an effective treatment for ED-SCLC with acceptable hematologic and non-hematologic toxicities.

Clinical Efficacy of Belotecan (CKD-602), Newly Developed Camptothecin Analog, in the 2nd Line Treatment of Relapsed Small Cell Lung Cancer / 결핵및호흡기질환

No abstract available.

Cytotoxic effects of Belotecan in the cervical cancer cell lines / 대한산부인과학회지

OBJECTIVE: In our domestic market, Belotecan (Camptobel(R), chongkeundang, Korea) is newly introduced recently. Belotecan has many advantages of improved water solubility and fewer side effects like severe diarrhea or GI bleeding compare to other camptothecin derivatives. In this study, primary focus is aiming to evaluate the effectiveness of belotecan by providing the cytotoxicity and apoptotic pathway on cervical cancer cells. METHODS: Cervical cancer cell line, HeLa and Caski were used. Belotecan applied on both cell lines and checked whether it has anti tumor effect on cancer cell by using MTT assay. DNA fragmentation and western blot was performed to confirm cellular apoptosis pathway. Also cDNA microarray and RT-PCR were serially carried out in order to identify responsible genes for apoptosis. RESULT: Dose- and time- dependent inhibition of cell proliferation is noted on the Belotecan applied HeLa and CaSki cervical carcinoma cell line by MTT assay. DNA fragmentation assay showed the DNA ladder indicating apopoptosis. Also apoptotic pathway and genes that are related with Belotecan activities are identified. Apoptosis, cell cycle, and drug metabolism related gene, and DNA repair gene were found to be differently regulated by treatment of Belotecan in HeLa cells. Among the DNA repair gene, RT-PCR reconfirmed the increased expression of CIB1(Calcium and intergrin binding 1), APEX1 (APEX nuclease 1) and the decresed expression of EXO1 (Exonuclease 1), WDR33 (WD repeat domain 33), and GADD45A (Growth arrest and DNA-damage-inducible, alpha). CONCLUSION: The first domestically introduced 1st line anti- tumor agent, Belotecan shows its excellent inhibiting action on cervical cancer cell proliferation by apoptotic pathway in this study. Also genetic alterations in cDNA microarray leads to the new fact that Belotecan, as a topoisomerase I inhibitor, is not only involved with apoptotic, cell cycle-related pathway but also involved in DNA repair.

The Synergism between Belotecan and Cisplatin in Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We wanted to demonstrate the anti-cancer effect and interaction between belotecan and cisplatin on gastric cancer cell line and we evaluated the mechanisms of this synergistic effect in vitro. MATERIALS AND METHODS: The growth inhibitory effect of belotocan and cisplatin against several gastric cancer cell lines (SNU-5, SNU-16 and SNU-601) was estimated by tetrazolium dye assay. The effect of a combination treatment was evaluated by the isobologram method. The biochemical mechanisms for the interaction between the drugs were analyzed by measuring the formation of DNA interstrand cross-links (ICLs) and DNA topo-I activity. RESULTS: Belotecan showed synergism with cisplatin for growth inhibitory effect on the gastric cancer cell lines SNU-5, and SNU-16, but this was subadditive on the SNU-601 cell line. The formation of DNA ICLs in SNU-16 cells by cisplatin was increased by combination with belotecan, but this was not affected in SNU-601 cells. The topo-I inhibition by belotecan was enhanced at high concentrations of cisplatin in SNU-16, but not in SNU-601 cells. CONCLUSION: Belotecan and cisplatin show various combination effect against gastric cancer cells. The synergism between cisplatin and belotecan could be the result of one of the following mechanisms: the modulating effect of belotecan on the repair of cisplatin-induced DNA adducts and the enhancing effect of cisplatin on the belotecan-induced topo-I inhibitory effect.