We report the results from a first-line phase III randomized clinical trial on metastatic colorectal cancer (mCRC) aimed at evaluating the effectiveness of adding bevacizumab (B) to standard ...first-line chemotherapy (CT).
mCRC patients were randomized to receive first-line CT (FOLFIRI or FOLFOX4) plus B (arm A) or CT only (arm B). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), response rate (ORR) and safety. Three hundred and fifty patients and 310 events were required to have an 80% statistical power to detect a difference in PFS between the groups.
Between November 2007 and March 2012, 376 patients were randomized. About 60% of patients received FOLFOX4 and 40% FOLFIRI. After a median follow-up of 36 months, 343 progressions and 275 deaths had been observed in the overall population. The median PFS was 9.6 95% confidence interval (CI) 8.2–10.3 and 8.4 (95% CI 7.2–9.0) months for arms A and B, respectively, with a hazard ratio of 0.86 (95% CI 0.70–1.07; P = 0.182). No statistically significant differences in OS or ORR were observed. B-containing regimens were associated with more frequent hypertension, bleeding, proteinuria and asthenia.
The addition of B to standard first-line CT for mCRC did not provide a benefit in terms of PFS, OS or ORR. Further research is warranted to better identify the target population.
NCT01878422.
Abstract Background Although Indocyanine green (ICG) is used to find sentinel nodes (SN) in patients with breast cancer (BC), its role in clinical practice is still debated, and needs a definitive ...validation to be included in the standard approach to finding sentinel nodes in breast cancer. Materials and methods To validate the ICG methods of detecting the SN in BC we have recently concluded a prospective validation trial. Patients with clinically node-negative, invasive early BC scheduled for breast surgery and SN biopsy were included in the trial. All the patients underwent SN detection using both the standard-of-care procedure using radioisotope technetium (99mTc) and the ICG, using the Photodynamic Eye camera. A comparison of the detection rate and the diagnostic accuracy of the two methods was performed to detect the equivalency of the two approaches. Results At the end of the enrolment, 301 patients were considered eligible and included in the trial, and 589 nodes were removed. Five hundred and eighty-three nodes (99%) were identified with ICG (median 2 nodes per patient) and 452 (76.7%) were identified with 99mTc (median 2 nodes per patient). A concordance index of 98.75% (CI, 95% = 97.1%–99.5%) was detected. The dosage given ranged from 0.3 to 1.4 ml. ICG was used in all patients eligible for SN biopsy without any significant acute side effects. Conclusions The index of concordance between 99mTc and ICG seems to be extremely high, suggesting that ICG could be validated as an alternative method to 99mTc in the detection of SN in BC.
Retinoic acid (RA) regulates stemness and differentiation in human embryonic stem cells (ESCs). Ewing sarcoma (ES) is a pediatric tumor that may arise from the abnormal development of ESCs. Here we ...show that RA impairs the viability of SK-ES-1 ES cells and affects the cell cycle. Cells treated with RA showed increased levels of p21 and its encoding gene,
. RA reduced mRNA and protein levels of SRY-box transcription factor 2 (SOX2) as well as mRNA levels of beta III Tubulin (
), whereas the levels of
increased. Exposure to RA reduced the capability of SK-ES-1 to form tumorspheres with high expression of SOX2 and Nestin. Gene expression of
and
was reduced in ES tumors compared to non-tumoral tissue, whereas transcript levels of
were significantly higher in tumors. For
and
, differences between tumors and control tissue did not reach statistical significance. Low expression of
and
, and high expression of
, were significantly associated with a poorer patient prognosis indicated by shorter overall survival (OS). Our results indicate that RA may display rather complex modulatory effects on multiple target genes associated with the maintenance of stem cell's features versus their differentiation, cell cycle regulation, and patient prognosis in ES.
The aims of the present study were to verify whether an innovative therapeutic strategy for the treatment of mild-moderate chronic cancer pain, passing directly from step I to step III of the WHO ...analgesic ladder, is more effective than the traditional three-step strategy and to evaluate the tolerability and therapeutic index in both strategies.
Patients aged 18 years or older with multiple viscera or bone metastases or with locally advanced disease were randomized. Pain intensity was assessed using a 0-10 numerical rating scale based on four questions selected from the validated Italian version of the Brief Pain Inventory. Treatment-specific variables and other symptoms were recorded at baseline up to a maximum follow-up of 90 days per patient.
Fifty-four patients were randomized onto the study, and pain intensity was assessed over a period of 2,649 days. The innovative treatment presented a statistically significant advantage over the traditional strategy in terms of the percentage of days with worst pain > or =5 (22.8 vs 28.6%, p < 0.001) and > or =7 (8.6 vs 11.2%, p = 0.023). Grades 3 and 4 anorexia and constipation were more frequently reported in the innovative strategy arm, although prophylactic laxative therapy was used less in this setting.
Our preliminary data would seem to suggest that a direct move to the third step of the WHO analgesic ladder is feasible and could reduce some pain scores but also requires careful management of side effects.
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