Docosahexaenoic acid (DHA)-paclitaxel has a unique pharmacokinetic profile that allows high concentrations of paclitaxel to be delivered to melanoma cells for prolonged periods compared with ...paclitaxel. We investigated the response rate and safety of weekly DHA-paclitaxel in metastatic melanoma patients. We enrolled chemotherapy-naive patients with metastatic nonchoroidal melanoma using the two-stage Fleming design. At least one response was needed in the first stage to proceed to the second stage. DHA-paclitaxel (500 mg/m/week by 1-h intravenous infusion) was administered for 5 weeks every 6-week cycle until disease progression, intolerable toxicity, or treatment refusal. Response and toxicity were assessed every 6 weeks and weekly, respectively. Thirty patients were enrolled. The patients' median age was 67 years (range: 29-86 years). The median number of treatment cycles was 2 (range: 1-6 cycles). Three patients (10%) had partial responses; one lasted 4 months, and two lasted 5.6 months. Fifteen patients (50%) had stable disease with a median duration of 2.8 months (range: 2.6-8.9 months). The median survival was 14.8 months. Neutropenia (10%) and musculoskeletal pain (10%) were the most common grade 3 and 4 toxicities, and fatigue (73%), skin rash (70%), and diarrhea (60%) were the most common side effects. As a single-agent therapy, DHA-paclitaxel was well tolerated in metastatic melanoma patients. Its efficacy as a first-line therapy for metastatic melanoma does not exceed that seen with other single-agent chemotherapies such as dacarbazine. Further evaluation of DHA-paclitaxel in combination with other chemotherapy or targeted agents could be considered.
Background. Liver metastasis develops in approximately two‐thirds of patients with recurrent uveal melanoma. Despite therapy, the median survival of those with liver metastasis is 5 to 7 months. The ...recognition of a grave prognosis associated with liver metastasis has led to evaluation of new modalities of therapy, including the use of regional therapies such as intrahepatic arterial chemotherapy and either embolization or chemoembolization of hepatic metastases. In this study, the results of an institutional experience over the past 2 decades are reviewed and prognostic factors that affect survival from the time the liver metastasis is diagnosed are assessed.
Methods. In this study of 201 patients with uveal melanoma involving the liver who were treated at M. D. Anderson Cancer Center between 1968 and 1991, the authors retrospectively reviewed the cases and compared the results of systemic therapies, hepatic infra‐arterial chemotherapies, and chemoembolization of liver metastases. Cox's multivariate analysis and stepwise logistic regression were then computed to determine significant prognostic variables.
Results. The systemic therapies produced a response rate of less than 1%. Chemoembolization was the most effective treatment, inducing responses in 36% of patients. Survival curves were calculated using the life‐table method of Kaplan and Meier. Patient‐and tumor‐related characteristics were examined and their relation to on survival from the time of diagnosis of liver metastasis was determined. Levels of serum alkaline phosphatase, total bilirubin, and lactic dehydrogenase plus response to treatment showed a strong relation to survival. In contrast, univariate analysis showed that patient age and gender, metastasis free interval, presence of extrahepatic metastasis, and type of therapy for liver metastasis did not influence survival. Multivariate stepwise regression analysis identified serum alkaline phosphatase and metastasis free interval as the main independent prognostic factors for survival after liver metastasis diagnosis.
Conclusions. Of the three modalities of therapy used for choroidal melanoma metastatic to the liver, only chemoembolization using cisplatin‐based regimens produced a meaningful response rate. Information from this analysis can be used to predict the outcome of patients with uveal melanoma metastatic to the liver. Patients with metastatic ocular melanoma confined to the liver should be treated with chemoembolization and should not be included in chemotherapy trials designed for cutaneous melanoma. Cancer 1995; 76:1665–70.
Peptide vaccination against tumor-associated antigens remains one of the most common methods of immunization in cancer vaccine clinical trials. Although peptide vaccination has been reported to ...increase circulating antigen-specific T-cells, they have had limited clinical efficacy and there is a necessity to increase their capacity to generate strong antitumor responses. We sought to improve the clinical efficacy of peptide-based vaccines in cancer immunotherapy of metastatic melanoma using a LHRH agonist (leuprolide) as adjuvant. Seventy HLA-A*0201 stage IIb-IV melanoma patients were vaccinated with class I HLA-A*0201-restricted gp100209-2M peptide and stratified for HLA-DP4 restriction. HLA-DP4 patients were also vaccinated with class II HLA-DP4-restricted MAGE-3243-258 peptide. Patients from both groups were randomized to receive 2 doses of leuprolide or not. Here we report the increase in PBMC TREC levels at week 24 after peptide vaccination, which was independent of the leuprolide treatment. This change was mirrored by a small increase in the TREC-enriched CD8CD45RAROCD27CD103, but not the TREC-enriched CD4CD45RAROCD31 T-cell population. Serum concentration of 2 important factors for thymopoiesis was measured: insulin growth factor 1 (IGF-1) levels were not changed, whereas a moderate increase in IL-7 levels was noted in the sera of all patients 6 weeks after vaccination. Increased expression of CD127 (IL-7 receptor-α) at week 24, compared with baseline, was only seen in the CD8CD45RAROCD27CD103 T-cell population. Our results suggest that leuprolide has no effect on thymic output when used as peptide vaccine adjuvant, but IFA-based peptide vaccination may unexpectedly affect the thymus by increasing thymic output of new T cells.
Treatment of patients with metastatic uveal melanoma is very challenging because the tumor commonly spreads to the liver, surgical resection of metastases is rarely possible, and there is no standard ...effective systemic therapy. We report the case of a 38-year-old man, who presented with metastatic involvement of the left ventricle as the first site of uveal melanoma recurrence 13 years after treatment of his primary tumor. The metastatic tumor was considered unresectable. We describe the patient's medical management over the next 3 years, the course of his disease, and the results of our review of the literature.
This phase I trial assessed the maximal tolerated dose (MTD) of dacarbazine in combination with lenalidomide in metastatic melanoma. Cohorts of three to six patients with metastatic melanoma without ...brain metastases were enrolled at each of three dose levels of dacarbazine: 600 mg/m², 800 mg/m², and 1000 mg/m² administered intravenously every 3 weeks. Lenalidomide (25 mg/day) was administered orally for 14 days followed by a 7-day rest. Safety was assessed every 3 weeks, and tumor response was evaluated every 6 weeks. An additional 10 patients were enrolled in an expansion cohort at MTD level. Twenty-eight chemotherapy-naive patients were enrolled. The MTD was determined to be dose level 2 (800 mg/m²). Three patients experienced a grade 4 adverse reaction; two pulmonary emboli and one cerebral ischemia. Two patients had a deep venous thrombosis. Of 27 patients assessable for disease response, two experienced a complete response and four experienced a partial response. The median overall survival was 10.6 months (range 1.6-46.0+ months). One patient had a small brain lesion at the baseline; 10 additional patients developed brain metastasis at 0-10.8 months after completion of study therapy. The combination of dacarbazine and lenalidomide is safe and well tolerated in patients with metastatic melanoma. Clinical activity was seen at the MTD level. Additional measures to prevent brain metastasis are needed for patients who achieve a response.
Reductive Quantum Phase Estimation Papadopoulos, Nicholas J C; Reilly, Jarrod T; John Drew Wilson ...
arXiv.org,
04/2024
Paper, Journal Article
Open access
Estimating a quantum phase is a necessary task in a wide range of fields of quantum science. To accomplish this task, two well-known methods have been developed in distinct contexts, namely, Ramsey ...interferometry (RI) in atomic and molecular physics and quantum phase estimation (QPE) in quantum computing. We demonstrate that these canonical examples are instances of a larger class of phase estimation protocols, which we call reductive quantum phase estimation (RQPE) circuits. Here we present an explicit algorithm that allows one to create an RQPE circuit. This circuit distinguishes an arbitrary set of phases with a fewer number of qubits and unitary applications, thereby solving a general class of quantum hypothesis testing to which RI and QPE belong. We further demonstrate a trade-off between measurement precision and phase distinguishability, which allows one to tune the circuit to be optimal for a specific application.
The angiopoietins Ang1 (ANGPT1) and Ang2 (ANGPT2) are secreted factors that bind to the endothelial cell-specific receptor tyrosine kinase Tie2 (TEK) and regulate angiogenesis. Ang1 activates Tie2 to ...promote blood vessel maturation and stabilization. In contrast, Ang2, which is highly expressed by tumor endothelial cells, is thought to inhibit Tie2 activity and destabilize blood vessels, thereby facilitating VEGF-dependent vessel growth. Here, we show that the inhibition of tumor xenograft growth caused by an Ang2-specific antibody (REGN910) is reversed by systemic administration of the Tie2 agonist Ang1. These results indicate that Ang2 blockade inhibits tumor growth by decreasing Tie2 activity, showing that Ang2 is a Tie2 activator. REGN910 treatment of tumors resulted in increased expression of genes that are repressed by Tie2 activation, providing further evidence that REGN910 inhibits Tie2 signaling. Combination treatment with REGN910 plus the VEGF blocker aflibercept reduced tumor vascularity and tumor perfusion more dramatically than either single agent, resulting in more extensive tumor cell death and more potent inhibition of tumor growth. Challenging the prevailing model of Ang2 as a destabilizing factor, our findings indicate that Ang2 plays a protective role in tumor endothelial cells by activating Tie2, thereby limiting the antivascular effects of VEGF inhibition. Thus, blockade of Ang2 might enhance the clinical benefits currently provided by anti-VEGF agents. .
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