Increased rates of local complication of central venous catheters in the targeted anticancer therapy era: a 2-year retrospective analysis.

PURPOSE: Totally implantable central venous accesses (port-a-cath) are often used for chemotherapy administration or prolonged intravenous infusions in cancer patients. Local and systemic complications may occur both during and after placement of port-a-cath despite the well-established techniques for its placement and care. Out of other catheter-related local complications, thrombosis and infections represent the most common. Complications related to central venous catheter may be associated with infusion of both conventional chemotherapy and molecularly targeted therapy. Incidence and nature of complications of central venous catheter have been well established for long-term chemotherapy. However, very sparse data exists on the incidence of complications of molecularly targeted therapies administered through a central venous catheter. Hence, we decided to retrospectively analyze the local complications of a central venous catheter in patients receiving molecularly targeted therapy and conventional chemotherapy, respectively. METHODS: Over a 2-year period, 459 devices were placed in two academic Italian institutions. Patients' characteristics, catheter-related complications, and their relationship with targeted therapy administration were retrospectively assessed. RESULTS: Catheter-related complications occurred in 30 out of the 459 analyzed cancer patients (7 %). Local complications occurred in 12 (40 %) and 18 (60 %) patients receiving standard chemotherapy and biological drugs, respectively. Eighteen (72 %) out of 25 patients developing biological complications (BC) were receiving biological drugs. Infusion of a biological drug through a central venous catheter has been shown to increase the risk of central venous catheter complications (p = 0.02). No difference between the incidence of complication between anti-angiogenic and anti-epidermal growth factor receptor (EGFR) agents was observed in our study despite the statistically significant early development of port-a-cath complication in the anti-EGFR group. Treatment with a biological drug and the stage of disease, in univariate analysis, had independent effect on the duration for development of catheter-related complications. CONCLUSIONS: Molecularly targeted therapy may influence the occurrence of BCs, i.e., infection and dehiscence. Onset of BCs occurred earlier in patients receiving biological drugs (more frequently with bevacizumab than with anti-EGFR therapy) than those undergoing traditional chemotherapy. Further studies are needed to ascertain the findings of our study and to elucidate the reason for the higher incidence of catheter-related complications.

Phase I/II study of the tumour-targeting human monoclonal antibody-cytokine fusion protein L19-TNF in patients with advanced solid tumours.

PURPOSE: L19-TNF is an armed antibody that selectively targets human TNF to extra domain B-fibronectin on tumour blood vessels. We performed a phase I/II first-in-man trial with L19-TNF monotherapy in metastatic solid cancer patients to study safety and signs of clinical activity. METHODS: Six cohorts of patients were treated with increasing (1.3-13 µg/kg) doses of intravenous L19-TNF on day 1, 3, and 5 of repeated 3-weekly cycles, and 12 colorectal cancer patients were treated at 13 µg/kg. PK, antibody formation, changes in lymphocyte subsets, 5-HIAA plasma levels as well as safety and clinical activity were analysed. RESULTS: Thirty-four patients received at least one L19-TNF dose. The serum half-life of L19-TNF at 13 µg/kg was 33.6 min, and maximum peak serum concentration was 73.14 µg/L. Mild chills, nausea and vomiting but no haemato- or unexpected toxicity were observed. Grade 3 lumbar pain in bone metastasis was the only dose-limiting toxicity found in one patient. Objective tumour responses were not detected. Transient stable disease occurred in 19 of 31 evaluable patients. CONCLUSIONS: Intravenous L19-TNF on day 1, 3, and 5 of a 3-weekly schedule was safe up to 13 µg/kg, but did not result in objective tumour responses. The maximally tolerated dose (MTD) was not reached, allowing for further dose escalation of L19-TNF possibly in combination with chemotherapy.

Arterial hypertension correlates with clinical outcome in colorectal cancer patients treated with first-line bevacizumab.

BACKGROUND: Arterial hypertension occurring during antiangiogenic therapy has been correlated with the biological inhibition of the vascular endothelial growth factor-related pathway and may represent a possible clinical marker for treatment efficacy. The aim of our study was to retrospectively assess if grades 2-3 hypertension were associated with response to bevacizumab, progression-free survival (PFS) and survival in metastatic colorectal cancer patients treated with first-line bevacizumab. PATIENTS AND METHODS: Patients with histologically proven, metastatic colorectal cancer receiving bevacizumab as first-line therapy in combination with irinotecan and 5-fluorouracil were eligible for our analysis. RESULTS: Thirty-nine metastatic colorectal cancer patients were eligible. Eight patients (20%) developed grades 2-3 hypertension. A partial remission was observed in six of eight cases with bevacizumab-related hypertension (75%) and in 10 of 31 (32%) patients with no hypertension (P = 0.04). Median PFS was 14.5 months for patients showing bevacizumab-related hypertension, while it was 3.1 months in those without hypertension (P = 0.04). Median overall survival was not reached in patients with hypertension while it was 15.1 months in the remaining cases (P = 0.11). CONCLUSIONS: Our data indicate that bevacizumab-induced hypertension may represent an interesting prognostic factor for clinical outcome in advanced colorectal cancer patients receiving first-line bevacizumab.

Epidermal growth factor receptor (EGFR) downstream signalling pathway in primary colorectal tumours and related metastatic sites: optimising EGFR-targeted treatment options.

We analysed the expression of activated (phosphorylated) Akt and MAPK in 98 cases of paired primary colorectal tumours and metastases with the aim to define better the epidermal growth factor receptor (EGFR)-related molecular profile of colorectal cancer as a tool for treatment selection. Among 47 (48%) EGFR-negative primary tumours, 35 cases (74%) were positive for phosphorylated Akt and MAPK. Among 51 (52%) EGFR-positive primary colorectal cancers, 13 (25%) cases were negative for phosphorylated Akt and 15 (29%) were negative for phosphorylated MAPK. In EGFR-negative metastases (56 cases, 55%), phosphorylated Akt was expressed in 41 (73%) and phosphorylated MAPK was expressed in 36 (64%) samples, whereas in EGFR-positive metastases, phosphorylated Akt and MAPK were negative in 14 (31%) and in 10 (22%) cases, respectively. Phosphorylated Akt expression in primary colorectal tumours changed from positive to negative in 16 (16%) paired metastases and from negative to positive in 13 (13%) related metastatic sites. Phosphorylated MAPK expression in primary tumours changed from positive to negative in 13 (13%) paired metastases and from negative to positive in 12 (12%) related metastatic sites. Our findings suggest that phosphorylated Akt and MAPK status in primary tumours does not correlate with Akt and MAPK status in corresponding metastases. EGFR downstream signalling pathway can be overactivated even in the absence of EGFR expression in a considerable proportion of patients.

[Paraneoplastic syndromes: a review]. / Le sindromi paraneoplastiche: revisione critica della letteratura.

Modern oncology often obtains good results against earlier neoplasms, whilst it's still in difficulties against the advanced ones. The knowledge of paraneoplastic syndromes is crucial both to cure patients and to do an earlier diagnosis. When we recognize a paraneoplastic syndrome that comes before the clinic beginning of a neoplasm, perhaps we save a life. This review discusses all the main paraneoplastic syndromes, focusing mainly on their clinical aspect and reminding the most commonly associated cancers.