Journal of Microelectronic Research 2010

https://scholarworks.rit.edu/meec_archive/1018/thumbnail.jp

Cisplatin plus gemcitabine in previously treated squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group

OBJECTIVES: This trial was conducted to evaluate the safety and efficacy of cisplatin plus gemcitabine in previously treated squamous cell carcinoma of the cervix. SUBJECTS AND METHODS: All women had measurable histologically confirmed squamous cell cervical cancer and a GOG performance status less than or equal to 2. The women were to receive cisplatin at 30 mg/m(2) plus gemcitabine at 800 mg/m(2) day 1 and day 8 every 28 days. RESULTS: Between February 2001 and May 2002, 32 eligible patients were entered. All women had received prior chemotherapy and 29 had received radiation. Twenty patients received platinum previously twice. The median time from primary treatment to recurrence was 21 months, but the median time from last prior chemotherapy was less than 2 months. A second phase of accrual was not indicated per the established stopping rules. There were 7 (21.9%) partial responses and median response duration was 2.1 months. Twelve additional women (37.5%) had stable disease. Nine women (28.1%) had increasing disease. Median time to progression was 3.5 months. There were no treatment-related deaths. Six women had grade 4 neutropenia, three had grade 4 anemia, and two had grade 4 thrombocytopenia. Grade 4 gastrointestinal toxicity occurred in two women and grade 4 anorexia occurred in one. CONCLUSIONS: This study suggests modest activity for the gemcitabine plus cisplatin doublet in previously treated squamous cell carcinoma of the cervix. The objective response rate of 22% is comparable to that of other active agents and combinations tested in this setting. Toxicities were primarily hematologic and generally manageable with dose reductions

Metastatic carcinoma of unknown primary with complete metabolic response following sorafenib-based chemotherapy

Background: The treatment of carcinoma of unknown primary based on histopathology and immunohistochemistry is generally chemotherapy. The use of molecular markers, genetic profiling platforms, and personalized medicine is under active investigation. Case Report: We report the case of a 56-year-old patient who presented to medical attention with palpable axillary adenopathy. Biopsy confirmed poorly differentiated adenocarcinoma. Formal staging revealed extensive metastatic disease to bone and liver. Initial chemotherapy proved ineffective. We describe the diagnostic evaluation, treatment, and achievement of durable remission using a novel sorafenib-based drug combination that was chosen through the application of a functional analytic laboratory platform. Conclusion: The clinical management of patients with carcinoma of unknown primary continues to present a considerable challenge for practicing oncologists. Laboratory platforms capable of examining cellular response to injury, growth factor withdrawal, and cytotoxic insult at the level of cellular function may provide insights for drug selection in this patient population

Platinum resistance in gynecologic malignancies: Response, disease free and overall survival are predicted by biochemical signature: A metabolomic analysis.

OBJECTIVE: Platinum resistance, defined as the lack of response or relapse within six months of platinum-based chemotherapy, is an important determinant of survival in gynecologic cancer. We used quantitative Mass Spectrometry to identify metabolic signatures that predict platinum resistance in patients receiving chemotherapy for gynecologic cancers. METHODS: In this study 47 patients with adenocarcinoma of the ovary or uterus who were candidates for carboplatin plus paclitaxel submitted blood for quantitation of metabolites and surgical specimens for the isolation 3-dimensional organoids used to measure individual patient platinum resistance, ex vivo. Results were correlated with response, time to progression and survival. RESULTS: Of 47 patients, 27 (64.3%) achieved complete remission with a mean time to progression of 1.9 years (± 1.5), disease-free survival of 1.7 years (± 1.4) and overall survival of 2.6 years (± 1.6) and a mean cisplatin lethal concentration 50% (LC50) = 1.15 μg/ml (range 0.4-3.1). Cisplatin LC50\u27s correlated with a non-significant decrease in complete remission (RR [95% CI] =0.76 [0.46-1.27]), diminished disease-free survival (median: 1.15 vs. 2.99 years, p = 0.038) and with biochemical signatures of 186 metabolites. Receiver operating curves (ROC) of lipid ratios, branched chain amino acids and the tryptophan to kynurenine ratio identified patients at the highest risk of relapse and death (AUC = 0.933) with a sensitivity of 92.0% and specificity of 86.0% (p \u3c 0.001). CONCLUSIONS: Metabolic signatures in gynecologic cancer identify patients at the highest risk of relapse and death offering new diagnostic and prognostic tools for management of the advanced gynecologic tumors