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

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

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

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

Acetates ; metabolism ; Animals ; Antineoplastic Agents, Phytogenic ; metabolism ; pharmacokinetics ; Biotransformation ; Diterpenes ; metabolism ; Paclitaxel ; metabolism ; Taxoids ; metabolism ; pharmacokinetics

A novel oral delivery system that TPGS modified docetaxel proniosomes, DTX-TPGS-PN, was developed and the characterization after hydration was observed. Firstly, Doce-TPGS-PN was optimized by investing the factors, including the type of surfactant, methods of adding TPGS, content of TPGS and the molar ratio of span40/cholesterol, which may affecting the particle size, encapsulation efficiency and instantaneous release of drug in the formulation. Then, the morphology, particle size, Zeta potential, encapsulation efficiency and in vitro release of the formulation were evaluated. The result showed that hydrated nanoparticles of DTX-TPGS-PNs were (93 ± 6.5) nm in size,(-83.95 ± 3.69) mV in zeta potential, (97.31 ± 0.60)% in encapsulation efficiency, exhibiting spherical morphology and biphasic release process that a low burst effect within the first 0.5 hour and a relative-sustained release for the next several hours in PBS. These results indicate the oral delivery system of DTX-TPGS-PN was successfully built with good properties.
Chemistry, Pharmaceutical ; methods ; Particle Size ; Polyethylene Glycols ; chemistry ; Taxoids ; chemistry ; pharmacology ; Vitamin E ; analogs & derivatives ; chemistry

OBJECTIVETo study the chemical constituents in seeds of Taxus mairei.

METHODPreparative HPLC, TLC and spectroscopic analyses were used to isolate and elucidate the chemical constituets in the plant.

RESULTSeven taxane diterpenoids were isolated from the seeds of T. mairei and identified as taxinine A(1), 9-deacetyltaxinine(2), 9-deacetyltaxinine E(3), 2-deacetyltaxinine(4), taxezopidine G(5), 2-deacetoxytaxinine J(6), 2-deacetoxytaxuspine C(7).

CONCLUSIONExcept compounds 5,6, all the compounds were obtained from seeds of this plant for the first time.

Adjuvant chemotherapy plays an important role in improving disease free and overall survival in women with high-risk early stage breast cancer. While more than seventy thousand women have enrolled in taxane-based adjuvant chemotherapy studies, interim and final results are available from several of these randomized phase III adjuvant studies. In this review, we will summarize the design and outcomes from the reported trials, and draw conclusions about the role adjuvant taxanes now play in the standard management of operable breast cancer. In aggregate, these studies show that adjuvant taxanes can improve important clinical outcomes beyond those achieved with anthracycline-based chemotherapy, without imparting prohibitive acute or chronic toxicities. Important questions are being addressed in ongoing adjuvant trials, including comparisons of combination to sequential therapy, direct comparisons between paclitaxel and docetaxel, and how to safely integrate targeted therapies into these highly active adjuvant regimens.
Breast Neoplasms* ; Breast* ; Chemotherapy, Adjuvant ; Drug Therapy ; Female ; Humans ; Paclitaxel ; Taxoids*

PURPOSE: Metastatic breast cancer patients are usually exposed to taxane and anthracycline as neoadjuvant, adjuvant and palliative chemotherapeutic agents. This study was designed to determine the efficacy and safety of the use of a gemcitabine and cisplatin (GP) combination treatment in patients with metastatic breast cancer that were pretreated with anthracycline and taxane. MATERIALS AND METHODS: We evaluated the use of a GP regimen (1,000 mg/m2 gemcitabine administered on days 1 and 8 plus 60 mg/m2 cisplatin administered on day 1 every 3 weeks) in 38 breast cancer patients who had received prior chemotherapy with anthracycline and taxane as an adjuvant or neoadjuvant therapy, or as a palliative therapy. RESULTS: The median patient age was 49 years (age range, 35~69 years). The overall response rate was 28.9% in 11 patients (95% confidence interval [CI], 14~44%). The median time to progression was 5.2 months (95% CI, 3.6~6.8 months). Median survival was 19.5 months (95% CI, 11.2~27.8 months). Major grade 3/4 hematological toxicity was due to leukopenia (36 of 157 cycles, 23.1%). Non-hematological toxicity was rarely severe; grade1/2 nausea and vomiting were observed in 37.8% of the patients. There were no treatment related deaths. CONCLUSIONS: Our results suggest that the use of gemcitabine plus cisplatin appears to be effective and has an acceptable toxicity profile in patients with advanced breast cancer that have been pretreated with anthracycline and taxane.
Breast ; Breast Neoplasms ; Bridged Compounds ; Cisplatin ; Deoxycytidine ; Humans ; Leukopenia ; Nausea ; Neoadjuvant Therapy ; Taxoids ; Vomiting

OBJECTIVE: This study was conducted to examine the effects of front-line chemotherapy on overall survival (OS) and postrecurrence survival (PRS) of patients with recurrent ovarian cancer, when stratifying the histologic type. METHODS: Five hundred and seventy-four patients with recurrent ovarian cancer with sufficient clinical information, including front-line chemotherapy, were analyzed. The pathologic slides were evaluated by central pathologic review. The patients were divided into two groups: group A (n=261), who underwent taxane plus platinum, and group B (n=313), who underwent conventional platinum-based chemotherapy without taxanes. RESULTS: The median age was 54 years (range, 14 to 89 years). Group A had significantly better median OS (45.0 months vs. 30.3 months, p<0.001) and PRS (23.0 months vs. 13.0 months, p<0.001) compared to group B. The OS and PRS were similar between the groups in patients with clear cell or mucinous histology. In contrast, among patients with non-clear cell, non-mucinous histologies, the OS and PRS of group A were significantly better than those of group B (OS, p<0.001; PRS, p<0.001). Multivariable analyses revealed that, among patients with non-clear cell, non-mucinous histologies, chemotherapy including taxane and platinum was an independent predictor of favorable survival outcomes. Conversely, in patients with clear cell or mucinous histology, taxane-including platinum-based combination chemotherapy did not improve the OS and PRS compared to a conventional platinum-based regimen which did not include taxanes. CONCLUSION: Since the emergence of taxane plus platinum, the prognosis of patients with recurrent ovarian cancer has improved. However, we here demonstrate that this improvement is limited to patients with non-clear cell, non-mucinous histologies.
Drug Therapy ; Drug Therapy, Combination ; Humans ; Mucins ; Ovarian Neoplasms* ; Platinum* ; Prognosis ; Taxoids