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 ; 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

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

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

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

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

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

PURPOSE: The purpose of this study was to evaluate efficacy and toxicity of irinotecan, leucovorin and 5-fluorouracil (FOLFIRI) as second-line treatment after failure of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX) for advanced gastric cancer. MATERIALS AND METHODS: Patients who received modified FOLFOX-4 as first-line treatment and then received sequential modified FOLFIRI for disease progression were included in this study. The modified FOLFIRI regimen consisted of irinotecan 150 mg/m2 in a 90-minute intravenous infusion on day 1, leucovorin (LV) 20 mg/m2 and 5-fluorouracil (5-FU) 400 mg/m2 as a bolus followed by 600 mg/m2 as a 22-hour infusion on days 1 and 2 with the same dose of 5-FU/LV of modified FOLFOX-4 every 2 weeks. RESULTS: A total of 32 patients received 126 courses of FOLFIRI chemotherapy. No complete response was achieved. Three patients (9.4%; 95% confidence interval [CI], 0 to 20.1%) achieved partial response, whereas 11 (34.4%; 95% CI, 17.0 to 51.8%) patients showed stable disease. Disease control rate (complete response, partial responses and stable diseases) was 43.8% (95% CI, 25.6 to 61.9%) and median follow up duration was 11.3 months (range, 2.23 to 37.9 months). Median time to progression was 2 months (95% CI, 1.49 to 2.51 months), and median overall survival from the start of FOLFIRI was 5.84 months (95% CI, 4.34 to 7.34 months). Toxicities were tolerable. CONCLUSION: Modified FOLFIRI as second-line chemotherapy after failure of the modified FOLFOX-4 in advanced gastric cancer was tolerable but showed a lower response rate. Further study about retrying 5-FU/LV with irinotecan after failure of the 5-FU/LV combined regimen is necessary in advanced gastric cancer.
Camptothecin ; Disease Progression ; Fluorouracil ; Follow-Up Studies ; Humans ; Infusions, Intravenous ; Leucovorin ; Organoplatinum Compounds ; Stomach Neoplasms

PURPOSE: The purpose of this study was to evaluate efficacy and toxicity of irinotecan, leucovorin and 5-fluorouracil (FOLFIRI) as second-line treatment after failure of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX) for advanced gastric cancer. MATERIALS AND METHODS: Patients who received modified FOLFOX-4 as first-line treatment and then received sequential modified FOLFIRI for disease progression were included in this study. The modified FOLFIRI regimen consisted of irinotecan 150 mg/m2 in a 90-minute intravenous infusion on day 1, leucovorin (LV) 20 mg/m2 and 5-fluorouracil (5-FU) 400 mg/m2 as a bolus followed by 600 mg/m2 as a 22-hour infusion on days 1 and 2 with the same dose of 5-FU/LV of modified FOLFOX-4 every 2 weeks. RESULTS: A total of 32 patients received 126 courses of FOLFIRI chemotherapy. No complete response was achieved. Three patients (9.4%; 95% confidence interval [CI], 0 to 20.1%) achieved partial response, whereas 11 (34.4%; 95% CI, 17.0 to 51.8%) patients showed stable disease. Disease control rate (complete response, partial responses and stable diseases) was 43.8% (95% CI, 25.6 to 61.9%) and median follow up duration was 11.3 months (range, 2.23 to 37.9 months). Median time to progression was 2 months (95% CI, 1.49 to 2.51 months), and median overall survival from the start of FOLFIRI was 5.84 months (95% CI, 4.34 to 7.34 months). Toxicities were tolerable. CONCLUSION: Modified FOLFIRI as second-line chemotherapy after failure of the modified FOLFOX-4 in advanced gastric cancer was tolerable but showed a lower response rate. Further study about retrying 5-FU/LV with irinotecan after failure of the 5-FU/LV combined regimen is necessary in advanced gastric cancer.
Camptothecin ; Disease Progression ; Fluorouracil ; Follow-Up Studies ; Humans ; Infusions, Intravenous ; Leucovorin ; Organoplatinum Compounds ; Stomach Neoplasms