Phase II study of epirubicin, oxaliplatin and docetaxel combination in metastatic gastric or gastroesophageal junction adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>This phase II study was designed to evaluate the activity and safety of a combination of epirubicin, oxaliplatin and docetaxel in metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.</p> <p>Methods</p> <p>Forty patients with measurable distant metastases received epirubicin 50 mg/m², docetaxel 60 mg/m²followed by oxaliplatin 100 mg/m²on day 1 of each 21-day cycle. Primary end point was response rates (RR).</p> <p>Results</p> <p>All patients were evaluable. The overall RR was 47.5% (95% confidence interval (CI) 32–63). The disease control was 80%. Median time for response was 6 weeks. Median time to progression was 6.3 months (95% CI 5.4–7.2) and the median overall survival time was 12.1 months (95% CI 10.7–13.5). Grade 3/4 neutropenia occurred in 50% of patients with two episodes of febrile neutropenia (5%). Other non-hematological grade 3 toxicities included sensory neuropathy in two patiens (5%), vomiting and mucositis in two patients (5%) and diarrhea in one patient (2.5%).</p> <p>Conclusion</p> <p>The combination of epirubicin, oxaliplatin and docetaxel was found to be effective and well tolerated in patiens with metastatic gastric or GEJ adenocarcinoma and maybe an appropriate regimen to be used in the neoadjuvant setting and with molecularly targeted agents.</p

Oxaliplatin, 5-fluorouracil/leucovorin and epirubicin as first-line treatment in advanced gastric carcinoma: a phase II study

The association between oxaliplatin and 5-fluorouracil (5-FU) has been extensively reported to improve prognosis of gastric cancer patients. The present study is aimed at evaluating response rate and the toxicity profile of the association with oxaliplatin, 5-FU/lecovorin and epirubicin in gastric cancer patients with locally advanced or metastatic disease. Thirty-six patients have been enrolled and 35 evaluated. The treatment schedule was oxaliplatin (100 mg m−2), 5-FU (400 mg m−2), leucovorin (40 mg m−2) and epirubicin (60 mg m−2) intravenously. administered every 3 weeks for 6 months, for a total of 185 therapy cycles . Response rate and toxicity were assessed according to the international WHO criteria. Every patient received a mean of 5.3 therapy cycles in a day-hospital setting. Sixteen of 35 patients (46%) showed an objective response, two complete response and 14 partial response. Median time to progression was 33 weeks with an overall median survival of 49 weeks. During the study, anaemia grade 3 and neutropenia grade 3 were observed in 9 and 11% of patients respectively. A grade 3 periferic sensorial neuropathy was observed in 6% of patients. No life threatening or cardiac toxicity was recorded. The regimen used showed anticancer activity against gastric carcinoma, a tolerable toxicity profile and excellent patient compliance

Proper interpretation of dissolved nitrous oxide isotopes, production pathways, and emissions requires a modelling approach.

Stable isotopes ([Formula: see text]15N and [Formula: see text]18O) of the greenhouse gas N2O provide information about the sources and processes leading to N2O production and emission from aquatic ecosystems to the atmosphere. In turn, this describes the fate of nitrogen in the aquatic environment since N2O is an obligate intermediate of denitrification and can be a by-product of nitrification. However, due to exchange with the atmosphere, the [Formula: see text] values at typical concentrations in aquatic ecosystems differ significantly from both the source of N2O and the N2O emitted to the atmosphere. A dynamic model, SIDNO, was developed to explore the relationship between the isotopic ratios of N2O, N2O source, and the emitted N2O. If the N2O production rate or isotopic ratios vary, then the N2O concentration and isotopic ratios may vary or be constant, not necessarily concomitantly, depending on the synchronicity of production rate and source isotopic ratios. Thus prima facie interpretation of patterns in dissolved N2O concentrations and isotopic ratios is difficult. The dynamic model may be used to correctly interpret diel field data and allows for the estimation of the gas exchange coefficient, N2O production rate, and the production-weighted [Formula: see text] values of the N2O source in aquatic ecosystems. Combining field data with these modelling efforts allows this critical piece of nitrogen cycling and N2O flux to the atmosphere to be assessed

Model scenario #2 – Isotopic composition of dissolved and emitted with a constant production rate and variable isotopic composition of the source.

<p>Model scenario #2 – Isotopic composition of dissolved and emitted with a constant production rate and variable isotopic composition of the source.</p

Diel variability in N₂O concentration and values at Bridgeport in the Grand River, Canada.

<p>The time axis begins at 00∶00 on 2007-06-26. Maximum production rate is in sync with the greatest ¹⁸O values of the source, while ¹⁵N of the source was constant. values between field and model data for N₂O saturation, ¹⁵N, and ¹⁸O values are 0.83, 0.68, and 0.30. This is similar to model scenario #4 (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090641#pone-0090641-g007" target="_blank">Figure 7</a>).</p

¹⁵N and ¹⁸O trajectories for dissolved and emitted N₂O in two supersaturated solutions with zero N₂O production.

<p>Initial dissolved isotopic values for the two dissolved N₂O solutions were ¹⁵N = −50‰, ¹⁸O = 10‰, and ¹⁵N = −10‰, ¹⁸O = 30‰. Both runs used an initial dissolved N₂O concentration of 1500% saturation. Note that in the ¹⁸O versus ¹⁵N plot, the dissolved N₂O curves do not pass through the tropospheric N₂O value due to the small equilibrium isotope effect.</p

Model scenario #1 – isotopic composition of dissolved and emitted N₂O with a variable production rate and constant isotopic composition of the source.

<p>Note, in panel D, the data points for emitted N₂O are masked by the data point for source N₂O.</p

Diel variability in N₂O concentration and values at Blair in the Grand River, Canada.

<p>The time axis begins at 00∶00 on 2007-06-26. Maximum production rate is in sync with the lowest ¹⁵N and ¹⁸O values of the source. values between field and model data for N₂O saturation, ¹⁵N, and ¹⁸O values are 0.78, 0.53, and 0.03. This is similar to model scenario #5 (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090641#pone-0090641-g008" target="_blank">Figure 8</a>).</p

Model scenario #3 – Isotopic composition of dissolved and emitted N₂O with a constant production rate and variable isotopic composition of the source.

<p> is reduced from 0.3 m/h to 0.1 m/h.</p