Taxane-based or platinum-based combination chemotherapy given concurrently with radiation followed by surgery resulting in high cure rates in esophageal cancer patients.

BACKGROUND: Preoperative chemoradiotherapy (CRT) is one standard option for localized esophageal or gastroesophageal junction (GEJ) cancer patients but an optimal concurrent chemotherapy combination is not established. METHODS: 412 patients with resectable (cT1N1M0 or cT2-4N0-3M0) esophageal or GEJ cancer treated at the MDACC between October 2002 and June 2016 were analyzed. Exposures: CRT with DF or FOX followed by surgery (trimodality; TMT). Main outcomes and measures: Primary endpoints were overall survival (OS) and disease-free survival (DFS). Univariate and multivariate Cox analyses were performed. RESULTS: Of the 412 patients analyzed, 264 (64%) received DF and 148 (36%) FOX. The median age was 60 years, and 95% had adenocarcinoma. The clinical complete response, positron-emission tomography response, and pathologic complete response rates were 73%, 73%, and 30%, respectively. Median follow-up was 60.4 months. Median OS for the entire cohort was 81.6 months (95% confidence interval [CI], 56.3-122.0); 81.6 months (95% CI, 55.9-not estimable) for the DF group and 67.7 months (95% CI, 41.6-not estimable) for the FOX group (P = .24). The median DFS was 45.6 months (95% CI, 33.1-61.7) for the entire cohort; 49.5 months (95% CI, 38.6-70.3) for DF and 33.0 months (95% CI, 18.1-70.4; P = .38) for FOX. Higher tumor location (unfavorable) and clinical complete response (favorable) were prognostic for both OS and DFS in the multivariate analysis. CONCLUSION: At our high-volume center, the outcome of 412 TMT esophageal cancer patients was excellent. Taxane-based chemotherapy produces nonsignificant favorable trend.

Discriminative and Quantitative Analysis of Antineoplastic Taxane Drugs Using a Handheld Raman Spectrometer.

This study was conducted to evaluate the ability of Raman spectroscopy (RS) to control antineoplastic preparations used for chemotherapy in order to ensure its physical and chemical qualities. Three taxane drugs: cabazitaxel (CBX), docetaxel (DCX) and paclitaxel (PCX) at therapeutic concentration ranges were analyzed using a handheld spectrometer at 785 nm. Qualitative and quantitative models were developed and optimized using a calibration set (n=75 per drug) by partial least square discriminant analysis and regression and validated using a test set (n=27 per drug). All samples were correctly assigned with an accuracy of 100%. Despite optimization, quantitative analysis showed limited performances at the lowest concentrations. The root mean square error of predictions ranged from 0.012 mg/mL for CBX to 0.048 mg/mL for DCX with a minimal coefficient of determination of 0.9598. The linearity range was validated from 0.175 to 0.30 mg/mL for CBX, from 0.40 to 1.00 mg/mL for DCX and from 0.57 to 1.20 mg/mL for PCX. Despite some limitations, this study confirms the potential of RS to control these drugs and also provides substantial advantages to secure the activity for healthcare workers. As a result of its rapidity and the uncomplicated use of a handheld instrument, RS appears to be a promising method to augment security of the medication preparation process in hospitals.

Prospective evaluation of [11C]Choline PET/CT in therapy response assessment of standardized docetaxel first-line chemotherapy in patients with advanced castration refractory prostate cancer.

PURPOSE: The aim of this study was to prospectively evaluate the value of [11C] Choline PET/CT in monitoring early and late response to a standardized first-line docetaxel chemotherapy in castration refractory prostate cancer (mCRPC) patients. METHODS: Thirty-two patients were referred for [11C] Choline PET/CT before the start of docetaxel chemotherapy, after one and ten chemotherapy cycles (or - in case of discontinuation - after the last administered cycle) for therapy response assessment. [11C] Choline uptake (SUVmax, SUVmean), CT derived Houndsfield units (HUmax, HUmean), and volume of bone, lung, and nodal metastases and local recurrence were measured semi-automatically at these timepoints. Change in SUVmax, SUVmean, HUmax, HUmean, and volume was assessed between PET 2 and 1 (early response assessment, ERA) and PET 3 and 1 (late response assessment, LRA) on a patient and lesion basis. Results of PET/CT were compared to clinically used RECIST 1.1 and clinical criteria based therapy response assessment including PSA for defining progressive disease (PD) and non-progressive disease (nPD), respectively. Relationships between changes of SUVmax and SUVmean (early and late) and changes of PSAearly and PSAlate were evaluated. Prognostic value of initial SUVmax and SUVmean was assessed. Statistical analyses were performed using SPSS. RESULTS: In the patient-based ERA and LRA there were no statistically significant differences in change of choline uptake, HU, and volume between PD and nPD applying RECIST or clinical response criteria. In the lesion-based ERA, decrease in choline uptake of bone metastases was even higher in PD (applying RECIST criteria), whereas in LRA the decrease was higher in nPD (applying clinical criteria). There were only significant correlations between change in choline uptake and PSA in ERA in PD, in LRA no significant correlations were discovered. Initial SUVmax and SUVmean were statistically significantly higher in nPD (applying clinical criteria). CONCLUSION: There is no significant correlation between change in choline uptake in [11C] Choline PET/CT and clinically routinely used objective response assessment during the early and late course of docetaxel chemotherapy. Therefore, [11C] Choline PET/CT seems to be of limited use in therapy response assessment in standardized first-line chemotherapy in mCRPC patients.

Pharmaceutical quality of docetaxel generics versus originator drug product: a comparative analysis.

INTRODUCTION: The aim of this study was to evaluate the quality of 31 commercially available generic formulations of docetaxel purchased in 14 countries by comparing their docetaxel content, impurity levels and pH versus those of the proprietary product Taxotere (Tx). RESEARCH DESIGN AND METHODS: Generic formulations were purchased in 14 countries in Asia, Africa, the Middle East and Latin America. Levels of docetaxel and impurities (chromatographic peaks above 0.05%) were obtained for each sample using reverse-phase liquid chromatography with ultraviolet detection. The pH of aqueous solutions of generic docetaxel formulations and Tx was also measured. A global evaluation of quality was conducted on each product using a multicriteria desirability analysis based on standards defined by the International Conference on Harmonisation guidelines and the US Pharmacopeia paclitaxel injection monograph. RESULTS: Most generic formulations contained a lower than expected amount of docetaxel and/or a high level of impurities: 21 generic docetaxel formulations had an average mass of docetaxel that was <90% of the expected mass and 23 generic docetaxel formulations had a total impurity content of >3.0%, almost twice the level of impurities in Tx 20 mg. In total, 33 impurities not present in Tx were detected in the generic samples. Desirability analysis demonstrated that none of the generic docetaxel formulations had composition characteristics similar to those of Tx. CONCLUSIONS: This study demonstrated that from an analytical point of view, 90% of the generic docetaxel formulations evaluated contained insufficient active drug, high levels of impurities or both. This has the potential to affect both efficacy and safety of the drug.

Standard treatment in advanced ovarian cancer in 2005: the state of the art.

What are standards? The oncology community expends considerable effort to review the results from definitive treatment studies and define recommendations for future studies, as well as standards of care for the community and patients who are not participating in clinical trials. This is a thoughtful and well-intentioned process but subject to considerable bias due to limitations in the data and/or their interpretation. While ovarian cancer is highly responsive to platinum-based therapy after initial cytoreductive surgery, there is a substantial risk of recurrence, which is accompanied by the emergence of drug-resistant disease. Better treatments with improved long-term outcomes are needed. From this perspective, standards can help to provide a baseline for assessing gaps in our current knowledge and defining priorities for future clinical trials. While not an exhaustive review, this study will focus on key clinical concepts that are guiding ovarian cancer research and treatment.