Receptor tyrosine kinases (RTKs) may facilitate tumor progression if activated aberrantly. The prognostic impact of human epidermal growth factor receptor 2 (HER2) overexpression and effectiveness of its therapeutic targeting is well established, but the effects on prognosis of overexpression of other RTKs is unknown. Here we evaluate the association of RTK expression and survival in breast cancer. PubMed was searched to identify studies evaluating the association between expression of RTKs other than HER2 and survival of women with breast cancer. Published data were extracted and computed into odds ratios (OR) for death at 5 years with 95% confidence intervals (CI). Data were pooled in a meta-analysis using the Mantel-Haenszel random-effect model. For studies reporting data for more than one RTK the lowest and highest OR were used for separate analyses. Sixteen studies comprising 11,056 patients were included in the analysis. There was an association between overexpression of RTKs and decreased 5-year OS and this was highly significant when using highest ORs from studies reporting more than one RTK (OR=2.42; 95% CI=1.92-3.06, P(0.001). Similar results were observed for 5-year BCSS. Worse OS was seen with overexpression of fibroblast growth factor receptor 2/3 (FGFR) (OR=3.81; 95% CI=1.79-8.11) and epidermal growth factor receptor (EGFR)/HER1 (OR=2.45; 95% CI=1.90-3.15). Overexpression of various RTKs is associated with poor outcomes. This data suggests the clinical evaluation of combination of agents against RTKs or relevant oncogenic nodes.
COBISS.SI-ID: 1948539
Tolerability to gemcitabine radiochemotherapy was evaluated in 33 patients with inoperable, locally advanced transitional-cell bladder cancers. The dose of 75 mg/m2 gemcitabine once a week, concurrently with standard radiotherapy of 60 Gy/6 weeks, was found to be acceptable. Eighty-one percentage of 3-year local progression-free survival suggests efficiency warranting further studies.
COBISS.SI-ID: 1227387
On the basis of investigation of the role of plasminogen activator we confirm that patients with high levels of uPA or/and PAI-1 in primary tumor benefit more from anthracyclin chemotherapy than from CMF chemotherapy.
COBISS.SI-ID: 843131
Elderly patients are often under-represented in clinical trials of metastatic colorectal cancer. We aimed toassess the efficacy and safety of bevacizumab plus capecitabine compared with capecitabine alone in elderly patientswith metastatic colorectal cancer.For this open-label, randomised phase 3 trial, patients aged 70 years and older with previously untreated,unresectable, metastatic colorectal cancer, who were not deemed to be candidates for oxaliplatin-based or irinotecanbasedchemotherapy regimens, were randomly assigned in a 1:1 ratio via an interactive voice-response system, stratifi edby performance status and geographical region. Treatment consisted of capecitabine (1000 mg/m orally twice a day ondays 114) alone or with bevacizumab (75 mg/kg intravenously on day 1), given every 3 weeks until disease progression,unacceptable toxic eff ects, or withdrawal of consent. Efficacy analyses were based on the intention-to-treat population.The primary endpoint was progression-free survival. The trial is registered with ClinicalTrials.gov, number NCT00484939.From July 9, 2007, to Dec 14, 2010, 280 patients with a median age of 76 years (range 7087) were recruitedfrom 40 sites across ten countries. Patients were randomly assigned to receive either bevacizumab plus capecitabine(n=140) or capecitabine only (n=140). Progression-free survival was signifi cantly longer with bevacizumab andcapecitabine than with capecitabine alone (median 91 months [95% CI 73114] vs 51 months [4263]; hazardratio 053 [041069]; p(00001). Treatment-related adverse events of grade 3 or worse occurred in 53 (40%) patientsin the combination group and 30 (22%) in the capecitabine group, and treatment-related serious adverse events in19 (14%) and 11 (8%) patients. The most common grade 3 or worse adverse events of special interest for bevacizumabor chemotherapy were hand-foot syndrome (21 [16%] vs nine [7%]), diarrhoea (nine [7%] vs nine [7%]), and venousthromboembolic events (11 [8%] vs six [4%]). Treatment-related deaths occurred in five patients in the combinationgroup and four in the capecitabine group. The most common any-grade adverse event of special interest forbevacizumab was haemorrhage (34 [25%] vs nine [7%]). The combination of bevacizumab and capecitabine is an effective and well-tolerated regimen for elderly patients with metastatic colorectal cancer.
COBISS.SI-ID: 1632123
If treatment of the axilla is indicated in patients with breast cancer who have a positive sentinel node, axillary lymph node dissection is the present standard. Although axillary lymph node dissection provides excellent regional control, it is associated with harmful side-eff ects. We aimed to assess whether axillary radiotherapy provides comparable regional control with fewer side-eff ects. Patients with T1%2 primary breast cancer and no palpable lymphadenopathy were enrolled in the randomised, multicentre, open-label, phase 3 non-inferiority EORTC 10981-22023 AMAROS trial. Patients were randomly assigned (1:1) by a computer-generated allocation schedule to receive either axillary lymph node dissection or axillary radiotherapy in case of a positive sentinel node, stratifi ed by institution. The primary endpoint was non-inferiority of 5-year axillary recurrence, considered to be not more than 4% for the axillary radiotherapy group compared with an expected 2% in the axillary lymph node dissection group. Analyses were by intention to treat and per protocol. The AMAROS trial is registered with ClinicalTrials.gov, number NCT00014612. Between Feb 19, 2001, and April 29, 2010, 4823 patients were enrolled at 34 centres from nine European countries, of whom 4806 were eligible for randomisation. 2402 patients were randomly assigned to receive axillary lymph node dissection and 2404 to receive axillary radiotherapy. Of the 1425 patients with a positive sentinel node, 744 had been randomly assigned to axillary lymph node dissection and 681 to axillary radiotherapy; these patients constituted the intention-to-treat population. Median follow-up was 6%1 years (IQR 4%1%8%0) for the patients with positive sentinel lymph nodes. In the axillary lymph node dissection group, 220 (33%) of 672 patients who underwent axillary lymph node dissection had additional positive nodes. Axillary recurrence occurred in four of 744 patients in the axillary lymph node dissection group and seven of 681 in the axillary radiotherapy group. 5-year axillary recurrence was 0%43% (95% CI 0%00%0%92) after axillary lymph node dissection versus 1%19% (0%31%2%08) after axillary radiotherapy. The planned non-inferiority test was underpowered because of the low number of events. The one-sided 95% CI for the underpowered non-inferiority test on the hazard ratio was 0%00%5%27, with a non-inferiority margin of 2. Lymphoedema in the ipsilateral arm was noted signifi cantly more often after axillary lymph node dissection than after axillary radiotherapy at 1 year, 3 years, and 5 years. Axillary lymph node dissection and axillary radiotherapy after a positive sentinel node provide excellent and comparable axillary control for patients with T1%2 primary breast cancer and no palpable lymphadenopathy. Axillary radiotherapy results in signifi cantly less morbidity.
COBISS.SI-ID: 1929595