Background Elderly patients are often under-represented in clinical trials of metastatic colorectal cancer. We aimed toassess the effi cacy and safety of bevacizumab plus capecitabine compared with capecitabine alone in elderly patientswith metastatic colorectal cancer.Methods 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. Effi cacy 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.Findings 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 fi ve 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%]).Interpretation The combination of bevacizumab and capecitabine is an eff ective and well-tolerated regimen for elderlypatients with metastatic colorectal cancer.
COBISS.SI-ID: 1632123
Background. Agents targeting the epidermal growth factor receptor (EGFR) are amongst the most extensively used of the targeted agents in the therapy of some of the most common solid tumors. Although they avoid many of the classic side effects associated with cytotoxic chemotherapy, they are associated with unpleasant cutaneous toxicities which can affect treatment compliance and impinge on patient quality of life. To date, despite a plethora of consensus recommendations, expert opinions and reviews, there is a paucity of evidence-based guidance for the management of the skin rash that occurs in the treatment of patients receiving EGFR-targeted therapies. Methods. A literature search was conducted as a first step towards investigating not only an evidence-based approach to the management of skin rash, but also with a view to designing future randomized trials. Results. The literature search identified seven randomized trials and a meta-analysis was conducted using the data from four of these trials involving oral antibiotics. The meta-analysis of the data from these four trials suggests that prophylactic antibiotics might reduce the relative risk of severe rash associated with EGFR-targeted agents by 4277%. Vitamin K cream was also identified as having a potential role in the management EGFR-targeted agent induced rash. Conclusions. This review and meta-analysis clearly identify the need for further randomized studies of the role of oral antibiotics in this setting. The results of the ongoing randomized trials of the topical application of vitamin K cream plus or minus doxycycline and employing prophylactic versus reactive strategies are eagerly awaited.
COBISS.SI-ID: 1577851
Background: To assess efficacy and toxicity of TPF induction chemotherapy and concomitant immunochemoradiotherapy with cetuximab and cisplatin in unresectable head and neck carcinoma.Methods: Treatment consisted of TPF induction chemotherapy (docetaxel 75 mg/m2 day 2; cisplatin, 75 mg/m2 day 2; and 5-fluorouracil 750 mg/m2 days 1-4; 4 cycles), followed by radiotherapy and concomitant weekly cetuximab, (250 mg/m2, after a loading dose of 400 mg/m2) and cisplatin (30 mg/m2).Results: 25/30 patients completed four cycles of induction chemotherapy. Six or more concomitant infusions of cisplatin and cetuximab were administered in 13/25 and 18/25 patients, respectively. The 2-year locoregional control, disease-free survival and overall survival were 47%, 47%, and 50%, respectively. Patients with grade 2 skin reaction to cetuximab had a superior outcome.Conclusion: The tested regimen was effective; however, cetuximab and low-dose cisplatin after induction TPF increased the treatment toxicity. A grade 2 skin rash correlated with improved efficacy.
COBISS.SI-ID: 1624443
Clonality analysis was performed in various clinical situations ranging from definitely neoplastic to putatively neoplastic lesions both for B and T-cell lymphocytes using the BIOMED-2 clonality assay and the method was validated in our institution.
COBISS.SI-ID: 1715835
Background. The aim of this study was to analyse whether the level of tissue inhibitor of meatalloproteinases (TIMP) 1 is associated with the tumour response and survival to preoperative radiochemotherapy in rectal cancer patients. Patients and methods. Ninety-two patients with histologically confirmed non-metastatic rectal cancer of clinical stage I- III were treated with preoperative radiochemotherapy, surgery and postoperative chemotherapy. Plasma TIMP-1 concentrations were measured prior to the start of the treatment with an enzyme-linked immunosorbent assay (ELISA). Results. Median follow-up time was 68 months (range: 3-93 months) while in survivors it was 80 months (range: 68-93 months). The 5-year locoregional control (LRC), disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) rates for all patients were 80.2%, 56.4%, 63.7% and 52.2%, respectively. The median TIMP-1 level was 185 ng/mL (range: 22-523 ng/mL) and the mean level (standard deviation) was 192 (87) ng/mL. Serum TIMP-1 levels were found to be significantly increased in patients with preoperative CRP)12 mg/L and in those who died from rectal cancer or had cT4 tumours. No correlation was established for age, gender, carcinoembriogenic antigene (CEA) level, platelets count, histopathological grade, response to preoperative therapy, resectability and disease reappearance. On univariate analysis, various parameters favourably influenced one or more survival endpoints: TIMP-1 (170 ng/mL, CRP (12 mg/L, platelets count (290 10E9/L, CEA (3.4mg/L, age (69 years, male gender, early stage disease (cN0 and/or cT2-3), radical surgery (R0) and response to preoperative radiochemotherapy. In multivariate model, LRC was favourably influenced by N-downstage, DFS by lower CRP and N-downstage, DSS by lower CRP and N-downstage and OS by lower TIMP-1 level, lower CRP and N-downstage. Conclusions. Although we did not find any association between pretreatment serum TIMP-1 levels and primary tumour response to preoperative radiochemotherapy in our cohort of patients with rectal cancer, TIMP-1 levels were recognized as an independent prognostic factor for OS in these patients.
COBISS.SI-ID: 1507963