We assessed the effectiveness of cetuximab plus chronomodulated irinotecan, 5-fluorouracil (5-FU), leucovorin (FA) and oxaliplatin (L-OHP) (chrono-IFLO) administered as neoadjuvant chemotherapy to ...increase the resectability of colorectal liver metastases.
This was a phase II prospective trial with rate of liver metastases resection as primary end point. Forty-three patients with unresectable metastases were enroled: 9 with metastases >5 cm; 29 with multinodular (>4) disease; 1 with hilar location; 4 with extrahepatic lung disease. Treatment consisted of cetuximab at day 1 plus chronomodulated irinotecan 5-FU, FA and L-OHP for 2-6 days every 2 weeks. After the first 17 patients, doses were reduced for irinotecan to 110 mg m⁻², 5-FU to 550 mg m⁻² per day and L-OHP to 15 mg m⁻² per day.
Macroscopically complete resections were performed in 26 out of 43 patients (60%) after a median of 6 (range 3-15) cycles. Partial response was noticed in 34 patients (79%). Median overall survival was 37 months (95% CI: 21-53 months), with a 2-year survival of 68% in the entire population, 80.6% in resected patients and 47.1% in unresected patients (P=0.01). Grade 3/4 diarrhoea occurred in 93% and 36% of patients before and after dose reduction.
Cetuximab plus chrono-IFLO achieved 60% complete resectability of colorectal liver metastases.
Ozone is a pollutant formed in the atmosphere by photochemical processes involving nitrogen oxides (NOx) and volatile organic compounds (VOCs) when exposed to sunlight. Tropospheric boundary layer ...ozone is regularly measured at ground stations and sampled infrequently through balloon, lidar, and crewed aircraft platforms, which have demonstrated characteristic patterns with altitude. Here, to better resolve vertical profiles of ozone within the atmospheric boundary layer, we developed and evaluated an uncrewed aircraft system (UAS) platform for measuring ozone and meteorological parameters of temperature, pressure, and humidity. To evaluate this approach, a UAS was flown with a portable ozone monitor and a meteorological temperature and humidity sensor to compare to tall tower measurements in northern Wisconsin. In June 2020, as a part of the WiscoDISCO20 campaign, a DJI M600 hexacopter UAS was flown with the same sensors to measure Lake Michigan shoreline ozone concentrations. This latter UAS experiment revealed a low-altitude structure in ozone concentrations in a shoreline environment showing the highest ozone at altitudes from 20–100 m a.g.l. These first such measurements of low-altitude ozone via a UAS in the Great Lakes region revealed a very shallow layer of ozone-rich air lying above the surface.
Dacarbazine (DTIC) is the only single-agent approved by the Food and Drug Administration for treating metastatic melanoma. With DTIC as single agent, an approximately 20% objective response rate can ...be achieved with median response duration of 5 to 6 months and complete response rates of 5%. Current status of DTIC single agent and DTIC-based combination chemotherapy has been extensively reviewed in this article. Moreover, future directions including new combination chemotherapies and/or new therapeutical approaches have been considered. The addition to DTIC of agents such as cisplatin, nitrosoureas and tubular toxins has been reported to yield high response rates, up to 40%, in single-institution phase II trials. Historically, promising combination regimens like BOLD (bleomycin, vincristine, lomustine and DTIC) and CVD (cisplatin, vinblastine and DTIC) have induced responses on metastatic lesions to the liver, bone and brain, commonly unresponsive to DTIC alone, even though have failed to produce impact on patient survival. Several other studies have suggested a significant enhancement of antitumor effect associated with the addition of tamoxifen to various cytotoxic regimens. The four-drug combination CBDT (cisplatin, carmustine, DTIC and tamoxifen) or "Dartmouth regimen" has yielded high response rates, up to 55%, with continuous, maintained, complete responses, up to 82 months, in a subset of patients, that is considerably longer than observed with other combinations. Some authors recommend CBDT as reference therapy, even though recently presented results of a randomized phase III trial of CBDT versus DTIC alone, show no statistical difference in survival between the two groups. While a survival benefit from DTIC-based chemotherapy or DTIC alone has never been shown in metastatic melanoma patients and, therefore, the survival has remained unchanged over the past 30 years, some long term survivors have been reported with the "Dartmouth regimen" and/or with high dose interleukin-2 (IL-2) based regimens whose role is going to be defined in prospective randomized phase III trials. On the other hand, the better understanding of the mechanisms responsible for melanoma chemoresistance and the development of new therapeutical strategies could change the scenario in the next future.
Abstract Young people (⩽40 years of age) with colorectal cancer (CRC) represent a distinct subgroup with more aggressive disease behaviour compared to older patients. We evaluate whether p53 and ...bcl-2 could be useful in identifying young patients at higher risk of tumour progression. We reviewed 1340 CRC patients with 58 patients ⩽40 years (4.2%). They had more frequent moderately or poorly differentiated mucinous adenocarcinomas (26% versus 12.3%, p = 0.03); higher advanced stage at diagnosis; shorter 5-year overall survival (49.8% versus 71%; p = 0.02); more frequent p53 positive (89.8% versus 72.6%, p < 0.05) and bcl-2 negative (88.0% versus 66.2%, p < 0.05) tumours; no difference in DNA content or proliferation indexes. Moreover, p53+ and bcl-2– resulted in being independent predictors of survival with shorter survival for the p53+/bcl-2– patients. Combining p53 and bcl-2, we could identify young CRC patients at higher risk of progression, who probably require development of a more sophisticated therapeutic approach based on identification of predictive factors.
Background: Capecitabine and oxaliplatin are both active anticancer agents in the treatment of patients with advanced colorectal cancer. The aim of this phase II study is to determine the efficacy ...and tolerability of combining oxaliplatin with capecitabine in the treatment of advanced non-pretreated colorectal cancer. Patients and methods: Forty-three chemotherapy-naïve patients were enrolled. Capecitabine 2500 mg/m2/day was administered orally twice a day continuously for 14 days and oxaliplatin 120 mg/m2 was administered as a 2-h infusion on day 1, repeated every 3 weeks. Results: Forty-three patients were assessable for toxicity and 39 for clinical activity: the main toxicity was grade 3 or 4 diarrhea, which occurred in 28% of the patients. The response rates were 44% 95% confidence interval (CI), 29.3% to 59.0% and 48.7% (95% CI 33.0% to 64.4%) (intention-to-treat and per protocol analysis, respectively). The median overall survival was 20 months (95% CI 12–28). Conclusions: Combining capecitabine and oxaliplatin yields promising activity in advanced colorectal cancer; therefore, the capecitabine dose we utilized is probably too high. The main toxicity is diarrhea, which is manageable with appropriate dose reductions.This combination may be preferable compared to a standard combination with infusional fluorouracil/leucovorin as it is more convenient and practical with similar efficacy. Thus, phase III trials are needed to clarify its role in the treatment of chemotherapy-naïve advanced colorectal cancer patients.
Small and midsized cities played a key role in the Industrial Revolution in the United States as hubs for the shipping, warehousing, and distribution of manufactured products. But as the twentieth ...century brought cheaper transportation and faster communication, these cities were hit hard by population losses and economic decline. In the twenty-first century, many former industrial hubs-from Springfield to Wichita, from Providence to Columbus-are finding pathways to reinvention. With innovative urban policies and design, once-declining cities are becoming the unlikely pioneers of postindustrial urban revitalization.Revitalizing American Citiesexplores the historical, regional, and political factors that have allowed some industrial cities to regain their footing in a changing economy. The volume discusses national patterns and drivers of growth and decline, presents case studies and comparative analyses of decline and renewal, considers approaches to the problems that accompany the vacant land and blight common to many of the country's declining cities, and examines tactics that cities can use to prosper in a changing economy. Featuring contributions from scholars and experts of urban planning, economic development, public policy, and education,Revitalizing American Citiesprovides a detailed, illuminating look at past and possible reinventions of resilient American cities.Contributors:Frank S. Alexander, Eugenie L. Birch, Paul C. Brophy, Steven Cochrane, Gilles Duranton, Sean Ellis, Kyle Fee, Edward Glaeser, Daniel Hartley, Yolanda K. Kodrzycki, Sophia Koropeckyj, Alan Mallach, Ana Patricia Muñoz, Jeremy Nowak, Laura W. Perna, Aaron Smith, Catherine Tumber, Susan M. Wachter, Kimberly A. Zeuli.
Summary Purpose: Capecitabine and oxaliplatin are both active anti-cancer agents in the treatment of patients with advanced colorectal cancer (ACRC). The aim of this dose-finding trial was to ...determine the maximum-tolerated dose (MTD), the dose-limiting toxicities (DLTs) and the activity of the combination in patients with advanced colorectal cancer. Patients and methods: Twenty-five chemotherapy-pretreated patients received the combination of capecitabine and oxaliplatin. Capecitabine was administered orally twice a day continuously for 14 days in doses ranging from 1650 to 2500 mg/m2/d, and oxaliplatin was administered as a two-hour infusion on day 1 using dose, ranges from 100 to 130 mg/m2 repeated every three weeks. Results: Twenty-five patients were assessable for toxicity, and DLTs were diarrhea (grade ≥ 3: 27%) and stomatitis (grade ≥3: 9%) at dose level VI. Dose level V (capecitabine 2500 mg/m2 and oxaliplatin 120 mg/m2) was found to be the MTD. Hematological toxicity was minimal, overall neuro-toxicity (grade 1–4) was 27% with 1% grade 3–4. A global response rate was 17% (95% confidence interval (95% Cl): 2%–32%) and the median overall survival was 12 months. Conclusion: The recommended dose for further phase II studies is capecitabine 2500 mg/m2/d with intermittent schedule and oxaliplatin 120 mg/m2 every three weeks. The toxicities were mainly gastrointestinal: diarrhea, stomatitis and vomiting. This combination should be studied in phase II trials in advanced colorectal.
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