OBJECTIVE: The aim of this study was to evaluate the efficacy and toxicity of topotecan, camptothecin analogue topoisomerase I inhibitor, as the combination therapy with platinum in patients with recurrent epithelial ovarian carcinoma and primary peritoneal carcinomatosis. METHOD: In this study, patients who were treated with topotecan between January 2000 and June 2007 at Asan Medical Center, Seoul, Korea were reviewed. Fifty-one patients with recurrent ovarian carcinoma and peritoneal carcinomatosis were included. These patients' data were analyzed by review of medical records and pathologic and laboratory reports retrospectively. Response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria for patients with measurable disease and CA-125 response criteria for patients with non-measurable disease. The toxicities were evaluated according to NCI CTC (Common Toxicity Criteria) version 3.0. RESULTS: The mean age of patients was 53.4 years (ranged between 37 and 69). Forty-four patients had been evaluated by RECIST criteria. The overall response rate was 22.8% (10/44). Platinum-sensitive patients showed more favorable response rate (26.9%) than platinum-resistant patients (16.7%), however, it was not significant statistically (p=0.425). Platinum-sensitive group had significantly longer response duration (12.14 vs. 3.33 months, p=0.022) and time-to-progression (11.34 vs. 7.33 months, p=0.042) than platinum-resistant group. Heavily pretreated group, three or more prior regimens were used, had no significant differences from another group. The most common adverse effect of topotecan in combination with platinum was hematologic toxicity; grade 3/4 neutropenia was 30.6%, anemia was 42.7%, and thrombocytopenia was 8.37% in total 265 cycles of chemotherapy, however, it was tolerable. CONCLUSION: Topotecan in combination with platinum is considered as effective regimen with acceptable toxicity in treating recurrent epithelial ovarian carcinoma and primary peritoneal carcinomatosis who have failed previous treatment with platinum-containing chemotherapy.
Anemia ; Camptothecin ; Carcinoma ; DNA Topoisomerases, Type I ; Humans ; Korea ; Medical Records ; Neoplasms, Glandular and Epithelial ; Neutropenia ; Ovarian Neoplasms ; Platinum ; Retrospective Studies ; Thrombocytopenia ; Topotecan

Animals ; Antineoplastic Agents, Phytogenic ; chemistry ; pharmacology ; therapeutic use ; Camptothecin ; analogs & derivatives ; chemistry ; pharmacology ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Humans ; Lung Neoplasms ; drug therapy ; Structure-Activity Relationship ; Topotecan ; chemistry ; therapeutic use ; Tumor Cells, Cultured ; drug effects

Animals ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Antineoplastic Agents, Phytogenic ; chemical synthesis ; chemistry ; pharmacology ; Camptothecin ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; DNA Damage ; Humans ; Topoisomerase I Inhibitors ; Topotecan ; chemical synthesis ; chemistry ; pharmacology ; Tumor Cells, Cultured ; drug effects

No abstract available.
Camptothecin ; Recurrence ; Small Cell Lung Carcinoma

Surgery is the best and the only treatment modality for cure if a patient has resectable gastric cancer. The outcome can be improved by a strategy of perioperative (neoadjuvant or adjuvant) chemotherapy or chemoradiotherapy. Whereas, advanced gastric cancer is treated primarily with chemotherapy; however, no chemotherapy regimen has been considered a standard. First-line chemotherapy generally includes fluoropyrimidine and cisplatin, sometimes with the addition of a third drug (epirubicin or docetaxel). In second-line setting, chemotherapy with single-agent irinotecan or docetaxel has emerged as a new standard of care. With improved understanding of the biology of gastric cancer and the identification of key signaling pathways, a number of promising molecularly-targeted agents have been studied that broaden the therapeutic options in the future. Regardless of the extent of disease or treatment modality, a multidisciplinary team approach is always desired since it can provide best treatment options for the patients.
Biology ; Camptothecin ; Chemoradiotherapy ; Cisplatin ; Humans ; Standard of Care ; Stomach Neoplasms ; Taxoids

OBJECTIVETo establish the mothod to dectect the microdialysis recovery of HCPT and to investigate the influencing factors, thus to supply experimental basis for in-vivo microdialysis of HCPT.

METHODThe in vitro recovery of HCPT was detected by concentration difference method (increment method and decrement method). The influence of flow rates, medium concentration and temperature on the HCPT recovery and the stability were studied.

RESULTThe recovery detected by increment method was the same as by decrement method. The recovery was independent of HCPT concentrations in the medium. The hydroxycamptothecine recovery had good stability and increased as the temperature rose.

CONCLUSIONMicrodialysis sampling can be used for the pharmacokinetic study of HCPT. Retrodialysis can be used for the determination of the HCPT in vivo recovery.

Camptothecin ; analogs & derivatives ; chemistry ; isolation & purification ; Drug Stability ; Microdialysis ; Temperature

AIMTo improve the profile of 20 (S)-camptothecin, a series of 20-O-linked camptothecin phenoxyacetic acid ester derivatives have been designed.

METHODSThese derivatives were synthesized by the method of acylation. Their chemical structures were confirmed with 1HNMR, IR, MS, and HRMS. The cytotoxicities of the compounds were tested by MTT assay. The in vivo antitumor activities of these esters were evaluated against mouse liver tumor H22 in mice.

RESULTSTwelve derivatives of camptothecin ester are new compounds.

CONCLUSIONIn vitro and in vivo antitumor activity has indicated that some derivatives appeared significantly more effective than topotecan in the H22 mouse liver tumoral model.

Animals ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Camptothecin ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; drug effects ; Esters ; chemistry ; Female ; Humans ; Inhibitory Concentration 50 ; Liver Neoplasms ; pathology ; Mice ; Mice, Inbred ICR ; Molecular Structure ; Neoplasm Transplantation ; Topotecan ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays

PURPOSE: This study evaluated the efficacy of neoadjuvant chemotherapy combining 5-flurouracil/folinic acid with irinotecan (FOLFIRI) in colorectal multiple liver metastases regardless of resectability. METHODS: Forty-four patients with multiple (at least two) colorectal liver metastases were enrolled at seven tertiary referral hospitals between May 2007 and September 2010. All patients received the FOLFIRI chemotherapeutic regimen. Response to chemotherapy was assessed after three cycles (6 weeks) and once more after six cycles (12 weeks) of treatment. RESULTS: Objective response was noted in 27 patients (61.4%) and 4 patients (9.1%) had progressive disease. Of 44 patients, 10 patients (22.7%) underwent curative surgery (R0 resection) and 34 patients did not receive R0 resection. Grades 3 to 4 hematological toxicity was noted in 12 patients (27.3%) and grades 3 to 4 nonhematologic toxicity was identified in 5 patients (11.4%). CONCLUSION: FOLFIRI chemotherapy as a neoadjuvant chemotherapy for multiple colorectal liver metastases regardless of resectability demonstrated the possibility of R0 resection, high rate of objective response, and tolerable toxicities in this study.
Camptothecin ; Colorectal Neoplasms ; Humans ; Liver ; Neoadjuvant Therapy ; Neoplasm Metastasis ; Prospective Studies ; Tertiary Care Centers

BACKGROUND: There has been a growing realization that a variety of anticancer drugs can induce apoptotic cell death. In the present study, an attempt was made to investigate the responsiveness of gastric cancer cells to various anticancer drugs and to identify which apoptosis-related proteins could be correlated to chemosensitivity. METHODS: Nine human Korean gastric cancer cell lines (SNU-1, -5, -16, -484, -601, -620, -638, -668, and -719) were analyzed. The cytotoxicity of each cell line to camptothecin, cisplatin, mitomycin C, vincristine, 5-FU, epirubicin, and doxorubicin was determined by using a MTT (dimethylthiazole- diphenyltetrazolium-bromide) assay. Apoptosis-related proteins (p53, p21, Bcl-2, Bcl-x, and Bax) were detected using a Western blot assay. RESULTS: Of the nine gastric cancer cell lines, SNU-1 was resistant while SNU-5 was sensitive to anticancer drugs. Mutated p53 was detected in all the cell lines. The highest expression of Bcl-2 was observed in SNU-1 while less or no expression of Bcl-2 was observed in SNU-5, -484, and -601. Bcl-xL was less expressed in SNU-5 than in the other cell lines. CONCLUSIONS: Chemosensitivity in gastric cancer cell lines was correlated mainly with the level of Bcl-2 and partly with that of Bcl-xL. There was no correlation between the chemosensitivity and other apoptosis-related proteins, such as p21, p53, Bax, and Bcl-xS in the studied gastric cancer cell lines.
Blotting, Western ; Camptothecin ; Cell Death ; Cell Line* ; Cisplatin ; Doxorubicin ; Epirubicin ; Fluorouracil ; Humans ; Mitomycin ; Stomach Neoplasms* ; Vincristine

PURPOSE: Little is known about outcomes in the use of third-line chemotherapy in cases of advanced gastric cancer (AGC). The primary aim of this retrospective study was to evaluate outcomes of docetaxel-based chemotherapy in patients with AGC that progressed after both oxaliplatin-based and irinotecan-based regimens. MATERIALS AND METHODS: Eligible patients were those with AGC who had previous chemotherapy including fluoropyrimidine and oxaliplatin as well as fluoropyrimidine and irinotecan and who received subsequent docetaxel-based chemotherapy. Thirty-five patients were retrospectively recruited from 5 medical centers in Korea. Patients received either weekly or 3 weekly with docetaxel +/- cisplatin. RESULTS: Thirty-one out of 35 patients were evaluated for treatment response. A total of 94 cycles of chemotherapy (median, 2; range, 1 to 7) were administered. The overall response rate was 14.3%, and the disease control rate was 45.7%. The median progression-free survival (PFS) was 1.9 months (95% confidence interval [CI], 1.1 to 2.7 months). The median overall survival (OS) was 3.6 months (95% CI, 2.8 to 4.4 months). PFS and OS were significantly prolonged in patients of the Eastern Cooperative Oncology Group, with performance status of 0 or 1 in multivariate analysis (PFS: hazard ratio[HR], 0.411; 95% CI, 0.195 to 0.868; p=0.020 and OS: HR, 0.390; 95% CI, 0.184 to 0.826; p=0.014, respectively). Four of the 35 patients enrolled in the study died due to infection associated with neutropenia. CONCLUSION: Our findings suggest that salvage docetaxel-based chemotherapy is a feasible treatment option for AGC patients with good performance status (PS), whereas chemotherapy for patients with poor PS (PS< or =2) should be undertaken with caution for those who previously failed oxaliplatin- and irinotecan-based regimens.
Camptothecin ; Disease-Free Survival ; Humans ; Korea ; Multivariate Analysis ; Organoplatinum Compounds ; Retrospective Studies ; Stomach Neoplasms ; Taxoids