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

A 75-year old man with esophageal cancer presented with mental status change and seizures. He was under cisplatinand developed several times of generalized tonic-clonic seizures. The EEG (electroencephalography) showed triphasic waves and slowed background activity. He was diagnosed with status epilepticus and encephalopathy caused by cisplatin. He was treated with anticonvulsants and cisplatin was replaced by docetaxel. His mentality recovered completely and he had no more seizure. We conclude that physician using cisplatin should be aware of this rare complication.
Anticonvulsants ; Cisplatin ; Electroencephalography ; Esophageal Neoplasms ; Seizures ; Status Epilepticus ; Taxoids

OBJECTIVE: Larotaxel is a new chemical structure drug, which has not been marketed worldwide. Accordingly, the standard identification and quantification methods for larotaxel remain unclear. The spectrometric analyses were performed for verifying weight molecular formula, molecular weight and chemical structure of larotaxel. Besides, a quantification method was developed for measuring larotaxel in the liposomes. METHODS: The molecular formula, molecular weight and chemical structure of larotaxel were studied by using mass spectrometry (MS), infra-red (IR), nuclear magnetic resonance (NMR) and ultraviolet-visible (UV-vis) spectrometric techniques. The absorption wavelength of larotaxel was investigated by UV-vis spectrophotometry full-wavelength scanning. Besides, a quantification method was developed by high performance liquid chromatography (HPLC), and then validated by measuring the encapsulation efficacy of larotaxel liposomes. RESULTS: The four spectral characteristics of larotaxel were revealed and the corresponding standard spectra were defined. It was confirmed that larotaxel had the structure of tricyclic diterpenoids, with the molecular formula of C45H53NO14, the molecular weight of 831.900 1, and the maximum absorption wavelength of 230 nm. The quantitative method of larotaxel was established by using HPLC with a reversed phase C18 column (5 μm, 250 mm×4.6 mm), a mobile phase of acetonitrile-water (75:25, volume/volume), and a detection wavelength of 230 nm. The validation study exhibited that the established HPLC method was stable, and had a high recovery and precision in the quantitative measurement of larotaxel in liposomes. In addition, a new kind of larotaxel liposomes was also successfully prepared. The particle size of the liposomes was about 105 nm, with an even size distribution. And the encapsulation efficiency of larotaxel in the liposomes was above 80%. CONCLUSION The present study offers reference standard spectra of larotaxel, including MS, IR, NMR, and UV-vis, and confirms the molecular formula, molecular weight and chemical structure of larotaxel. Besides, the study develops a rapid HPLC method for quality control of larotaxel liposomes.
Chromatography, High Pressure Liquid ; Liposomes ; Magnetic Resonance Spectroscopy ; Taxoids

The discovery of hydroxylases in the anticancer drug taxol biosynthesis pathway is a hotspot and difficulty in current research. In this study, a new hydroxylase gene TcCYP725A22 (GenBank accession number: MF448646.1) was used to construct a sub-cellular localization vector pCAMIBA1303-TcCYP725A22-EGFP to get the transient expression in onion epidermal cells. Laser confocal microscopy revealed that the protein encoded by this gene was localized in the cell membrane. Furthermore, the recombinant plant expression plasmid pBI121-TcCYP725A22 was constructed. After transient transformation to the Taxus chinensis mediated by Agrobacterium tumefaciens LBA4404, qRT-PCR and LC-MS were utilized to analyze the effects of TcCYP725A22 overexpression on the synthesis of taxol. The results showed that, in the TcCYP725A22 overexpressed cell line, expression levels of most defined hydroxylase genes for taxol biosynthesis were increased, and the yield of taxanes were also increased. It was concluded that the hydroxylase gene TcCYP725A22 is likely involved in the biosynthetic pathway of taxol.
Biosynthetic Pathways ; Mixed Function Oxygenases ; Paclitaxel ; Taxoids ; Taxus

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

Paclitaxel is one of the taxoid-antineoplastic agents. These agents are used in the treatment of breast, lung and ovary cancer. Nail changes due to treatment with the taxanes (mainly docetaxel) are reported in 30~40 percent of patients. Paclitaxel is not commonly associated with dermatological reactions, although localized skin reactions and tissue necrosis following extravasation have been reported. Reports of the incidence of nail changes associated with paclitaxel is noted as the pigmentation or discoloration of the nail bed, vary from 2~20%. We report a patient with onycholysis and subungual suppuration during treatment with paclitaxel.
Breast ; Humans ; Incidence ; Lung ; Nails ; Necrosis ; Onycholysis ; Ovarian Neoplasms ; Paclitaxel ; Pigmentation ; Skin ; Suppuration ; Taxoids

PURPOSE: Breast cancer is heterogeneous disease and the response to chemotherapeutic agents is also heterogeneous from patient to patient. Chemotherapy response assay is in vitro test that is performed to evaluate the degree of tumor growth inhibition by chemotherapy drugs. In this study, we performed the chemotherapy response assay using adenosine triphosphate (ATP-CRA) in breast cancer patients and assessed the clinical availability. METHODS: Sixty five breast cancer patients were enrolled in this study. Cancer cells were evenly divided and treated with commonly used chemotherapeutic drugs in breast cancer (doxorubicin, epirubicin, 5-fluorouracil, paclitaxel, docetaxel, vinorelbine, and gemcitabine). To verify in vitro ATP-CRA indirectly, we analyzed the correlation between cell death rate (CDR) of doxorubicin and epirubicin, and between doxorubicin and paclitaxel. We also analyzed the mean CDR of doxorubicin, epirubicin and paclitaxel by HER2 status. RESULTS: We could successfully perform the ATP-CRA in 60 patients (95.2%). In all cases, we can get the results within 7 days. The range of CDR was very wide, from 0 to more than 50%, except gemcitabine. Epirubicin showed the highest mean CDR (39.9%) and doxorubicin, paclitaxel in order. According to the chemosensitivity index, paclitaxel is the most frequently first-ranked and doxorubicin, epirubicin in order. Correlation coefficient between the cell death rate of doxorubicin and epirubicin is 0.4210 and 0.1299 between paclitaxel and doxorubicin. In HER2 positive group, mean CDR of paclitaxel, epirubicin and doxorubicin was higher than in HER2 negative group, even though epirubicin and doxorubicin were not statistically significant (p=0.018, p=0.114, p=0.311, respectively). CONCLUSION: ATP-CRA showed heterogeneous results in individual patients. ATP-CRA was successful and can be performed within short time period. According to our in vitro study, it showed similar results with in vivo study but for the clinical use, the prospective randomized controlled trial should be preceded.
Adenosine Triphosphate ; Breast ; Breast Neoplasms ; Cell Death ; Deoxycytidine ; Doxorubicin ; Epirubicin ; Fluorouracil ; Humans ; Paclitaxel ; Polyphosphates ; Taxoids ; Vinblastine

PURPOSE: To estimate the effect and toxicity of bimonthly low-dose leucovorin (LV) and fluorouracil (5-FU) bolus plus continuous infusion(LV5FU2) with docetaxel combination chemotheraphy in patients with inoperable or postoperative relapsed gastric cancer. MATERIALS AND METHODS: Total 27 patients are enrolled in this study. LV 20 mg/m2 (bolus), 5FU 400 mg/m2 (bolus), 5-FU 600 mg/m2 (24-hour continuous infusion) on day 1, 2, 15, and 16, docetaxel 60 mg/m2 (1-hour infusion) on day 15 every 4 weeks. RESULTS: Total of 141 cycles were administered and response rate were 36.8% with 2 complete response (10.5%) and 5 partial response (26.3%) in 19 evaluable patients. The median response duration is 8.1 months (95% CI, 4.0~12.1). The median progression-free survival time is 6.7 months (95% CI, 5.0~8.5) and the median overall survival time is 11.9 months (95% CI, 4.8~19.1). The grade 3-4 toxcity of neutropenia (24.8%) and anemia (11.3%), neutropenic fever (2.8%) is observed. The grade 1 toxcity of injection site reaction is observed all patients and the grade 1-2 toxcity of alopecia is observed 60%. CONCLUSIONS: LV5FU2 with docetaxel combination chemotheraphy is effective and tolerable in patients with inoperable or postoperative relapsed gastric cancer.
Alopecia ; Anemia ; Disease-Free Survival ; Drug Therapy, Combination ; Fever ; Fluorouracil ; Humans ; Leucovorin ; Neutropenia ; Stomach Neoplasms ; Taxoids

Anaplastic thyroid carcinoma (ATC) is a rare type of malignancy of thyroid follicular cell origin. It is one of the most aggressive human cancers, and typically associated with a fatal prognosis. Most patients are presenting as locally advanced and systemically disseminated disease. A single mode of therapy, whether it is surgery, chemotherapy, or radiotherapy, fails to afford significantly favorable outcomes. While multimodality approaches may enhance the treatment response to a small degree, such implementations of these modalities are often impractical as many patients are of old age and are unable to tolerate the intensity of treatments. As in many other types of carcinomas, radical resection may be the mainstay of therapy for ATC, but surgery itself is seldom possible for this condition. Even with aggressive surgical therapy for those invasive ATCs, there is no evidence of decreased recurrence rates, while only the post-surgical morbidity rates increase. One chemotherapeutic agent that seems to demonstrate some effect against ATC is adriamycin, which is more effective when administered in combination, and is also known to act synergistically with radiotherapy. A commonly employed treatment modality is the combination therapy of adriamycin and cisplatin administration with hyperfractionated radiation therapy. Other chemotherapeutic agents proven to be effective are taxanes such as paclitaxel and docetaxel. Despite of disappointing result of conventional radiotherapy, however, hyperfractionated radiation therapy and combined chemotherapy has been suggested to improve survival rates by some institutions, while others disagree. The dismal results of conventional treatments for ATCs have stimulated the investigation for new therapeutic methods with improved outcome. There have been a number of trials of new materials or therapeutic methods. In recent studies, some trials were partially successful or promising in vitro or in vivo. The examples of these trials are; redifferentiation therapies, molecular targeted therapies, and some other miscellaneous methods. Although the observations may suggest that some of the methods may have a therapeutic effect on ATCs, or may act as an adjunct to other primary treatment modality, the efficacy and safety have not been ascertained yet in human trials, and further confirmation through in-depth studies are required.
Cisplatin ; Doxorubicin ; Humans ; Molecular Targeted Therapy ; Paclitaxel ; Prognosis ; Recurrence ; Survival Rate ; Taxoids ; Thyroid Gland ; Thyroid Neoplasms

PURPOSE: The objective of this study was to test the efficacy and toxicity of adriamycin plus docetaxel as the primary chemotherapy for women with advanced breast carcinoma, and including those patients with inflammatory breast cancer. Our study also evaluated the clinicopathologic factors influencing the response rate to neoadjuvant chemotherapy. METHODS: Twenty-eight patients who underwent neoadjuvant chemotherapy between 2002 and 2004 were included for this study. The patients were treated with adriamycin (50 mg/m2; intravenous bolus) followed by docetaxel (75 mg/m2; 1-hr intravenous infusion) on the first day of each cycle for an average four cycles. We analysed the response rate to adjuvant chemotherapy by reviewing the post operative pathologic report. Additionally we compared the clincopathologic factors related to the response rate. Statistical analyses were performed with 2-tests and using SPSS 11.0. RESULTS: The mean age at diagnosis was 48.9 yr old (range 29-63 yr). The tumoral response to neoadjuvant chemotherapy was, 3 patients (10.7%) showed a complete response (CR), 21 patients (75%) showed a partial response (PR). and which about lymph node were that 15 patients (75%) have shown responder, 5 patients (25%) have shown non-responder. The overall response rate to neoadjuvant chemotherapy was 85.7%. The preoperative serum-CEA level was influenced the response rate to neoadjuvant chemotherapy (p=0.025). Grade 3 or 4 neutropenia was recorded in 81.9% of the patients (N=59/72). Grade 3 or 4 anemia was recorded in 2.8% of the patients. CONCLUSION: Neoadjuvant chemotherapy with adriamycin plus docetaxel was effective treatment for patients with locally advanced breast cancer. The preoperative serum CEA level colud be the important factor for the neoadjuvant chemotherapy response rate.
Anemia ; Breast ; Breast Neoplasms ; Chemotherapy, Adjuvant ; Doxorubicin ; Female ; Humans ; Inflammatory Breast Neoplasms ; Lymph Nodes ; Neutropenia ; Taxoids