M. G. Zampino

Best choice of central venous insertion site for the prevention of catheter-related complications in adult patients who need cancer therapy: a randomized trial

BACKGROUND Central venous access is extensively used in oncology, though practical information from randomized trials on the most convenient insertion modality and site is unavailable. METHODS Four hundred and three patients eligible for receiving i.v. chemotherapy for solid tumors were randomly assigned to implantation of a single type of port (Bard Port, Bard Inc., Salt Lake City, UT), through a percutaneous landmark access to the internal jugular, a ultrasound (US)-guided access to the subclavian or a surgical cut-down access through the cephalic vein at the deltoid-pectoralis groove. Early and late complications were prospectively recorded until removal of the device, patients death or ending of the study. RESULTS Four hundred and one patients (99.9%) were assessable: 132 with the internal jugular, 136 with the subclavian and 133 with the cephalic vein access. The median follow-up was 356.5 days (range 0-1087). No differences were found for early complication rate in the three groups {internal jugular: 0% [95% confidence interval (CI) 0.0% to 2.7%], subclavian: 0% (95% CI 0.0% to 2.7%), cephalic: 1.5% (95% CI 0.1% to 5.3%)}. US-guided subclavian insertion site had significantly lower failures (e.g. failed attempts to place the catheter in agreement with the original arm of randomization, P = 0.001). Infections occurred in one, three and one patients (internal jugular, subclavian and cephalic access, respectively, P = 0.464), whereas venous thrombosis was observed in 15, 8 and 11 patients (P = 0.272). CONCLUSIONS Central venous insertion modality and sites had no impact on either early or late complication rates, but US-guided subclavian insertion showed the lowest proportion of failures.

The management of colorectal liver metastases: Expanding the role of hepatic resection in the age of multimodal therapy

Colorectal cancer (CRC) caused nearly 204,000 deaths in Europe in 2004. Despite recent advances in the treatment of advanced disease, which include the incorporation of two new cytotoxic agents irinotecan and oxaliplatin into first-line regimens, the concept of planned sequential therapy involving three active agents during the course of a patients treatment and the integrated use of targeted monoclonal antibodies, the 5-year survival rates for patients with advanced CRC remain unacceptably low. For patients with colorectal liver metastases, liver resection offers the only potential for cure. This review, based on the outcomes of a meeting of European experts (surgeons and medical oncologists), considers the current treatment strategies available to patients with CRC liver metastases, the criteria for the selection of those patients most likely to benefit and suggests where future progress may occur.

Treatments for colorectal liver metastases: A new focus on a familiar concept

A major challenge for the management of advanced-colorectal-cancer is the multidisciplinary approach required for the treatment of liver metastases. Reducing the burden of liver metastases with liver-directed therapy has an important impact on both survival and health-related quality of life. This paper debates the rationale and current liver-directed approaches for colorectal liver metastases based on the evidence of literature and new clinical trials. Surgery is the gold standard, when feasible, and its the main treatment goal for patients with potentially-resectable disease as a means of prolonging progression-free survival. Better tumor response rates with modern systemic therapy mean that more unresectable patients are now down-staged for radical resection following conversion therapy but for other patients, additional procedures are needed. In multiple unilobar disease, when the projected remnant liver is <30% of the total liver, portal embolization or selective-internal-radiation-therapy (SIRT) can induce hypertrophy of the healthy liver, leading to resectability. In multiple bilobar disease, in situ destruction of non-resectable lesions by minimally invasive techniques may be associated with liver resection to achieve potential curative intent. Other palliative liver-directed approaches, such as SIRT or intra-hepatic chemotherapy (HAI), which are associated with higher response rates, may also have role in down-staging patients for resection. Until recently, such technologies have not been validated in prospective controlled trials. However in the light of new Phase 3 data for SIRT as well as for HAI combined with modern therapies or radiofrequency ablation in the first- and second-line setting, the clinical value of these treatments needs to be re-appraised.

Preoperative versus postoperative docetaxel–cisplatin–fluorouracil (TCF) chemotherapy in locally advanced resectable gastric carcinoma: 10-year follow-up of the SAKK 43/99 phase III trial

BACKGROUND Fluorouracil-based adjuvant chemotherapy in gastric cancer has been reported to be effective by several meta-analyses. Perioperative chemotherapy in locally advanced resectable gastric cancer (RGC) has been reported improving survival by two large randomized trials and recent meta-analyses but the role of neoadjuvant chemotherapy and optimal regimen remains to be determined. We compared a neoadjuvant with adjuvant docetaxel-based regimen in a prospective randomized phase III trial, of which we present the 10-year follow-up data. PATIENTS AND METHODS Patients with cT3-4 anyN M0 or anyT cN1-3 M0 gastric carcinoma, staged with endoscopic ultrasound, computed tomography, bone scan, and laparoscopy, were assigned to receive four 21-day/cycles of docetaxel 75 mg/m(2) day 1, cisplatin 75 mg/m(2) day 1, and fluorouracil 300 mg/m(2)/day over days 1-14, either before (arm A) or after (arm B) gastrectomy. Event-free survival was the primary end point, whereas secondary end points included overall survival, toxicity, down-staging, pathological response, quality of life, and feasibility of adjuvant chemotherapy. RESULTS This trial was activated in November 1999 and closed in November 2005 due to insufficient accrual. Of the 70 enrolled patients, 69 were randomized, 34 to arm A and 35 to arm B. No difference in EFS (2.5 years in both arms) or OS (4.3 versus 3.7 years, in arms A and B, respectively) was found. A higher dose intensity of chemotherapy was observed in arm A and more frequent chemotherapy-related serious adverse events occurred in arm B. Surgery was safe after preoperative chemotherapy. A 12% pathological complete response was observed in arm A. CONCLUSION Docetaxel/cisplatin/fluorouracil chemotherapy is promising in preoperative setting of locally advanced RGC. The early stopping could mask the real effectiveness of neoadjuvant treatment. However, the complete pathological tumour responses, feasibility, and safe surgery warrant further investigation of a taxane-based regimen in the preoperative setting.

A FOLFIRI-induced complete tumor response in a patient with FOLFOX-refractory metastatic duodenal adenocarcinoma

1Division of New Drugs Development and Clinical Pharmacology, European Institute of Oncology Ripamonti 435 Milan, Italy, 2Department of Pathology, European Institute of Oncology Ripamonti 435 Milan, Italy, 3Division of Abdomino-Pelvic Surgery, European Institute of Oncology Ripamonti 435 Milan, Italy, 4Division of Gynecology, European Institute of Oncology Ripamonti 435 Milan, Italy, 5Division of Nuclear Medicine, European Institute of Oncology Ripamonti 435 Milan, Italy and 5Divison of Radiology, European Institute of Oncology Ripamonti 435 Milan, Italy

Enhancement of in vivo monoclonal antibody targeting with recombinant interferon and cytokines

Up to now a number of studies have been performed to determine whether the combined use of cytokines and monoclonal antibodies (MAbs) directed against tumor-associated antigens (TAA) can increase the sensitivity of radioimmunoscintigraphy (RIS). It well known that human natural and recombinant interferons can enhance the cell surface expression of HLA Class I and II antigens as well as some specific tumor antigens, but there is scanty and conflicting information about the expression and shedding of TAA. Some authors reported that alpha-IFN enhances the expression of a melanoma-associated antigen (MAA), recognized by conventional antiserum. Other authors have found no changes in the expression of MAA identified by MAbs (17, 18). In a pilot study on patients with malignant melanoma Rosenblum demonstrated an increase in tumor uptake of the anti-melanoma MAb 96.5 after IFN administration. In our study we performed immunoscintigraphy with the anti-melanoma MAb 225.28S in the same patient before and after IFN administration in different doses. We point out the difference in biodistribution in different organs and in blood clearance and discuss the possibility to improve the sensitivity of RIS.

Subcutaneous low-dose interleukin-2 plus alpha interferon in advanced malignant melanoma

Aims and Background Interferon (IFN) and interleukin-2 (IL-2) have been proven to be active agents in the treatment of malignant melanoma, but the most effective doses of these cytokines were often associated to important side effects and poor patient compliance. Recently, the subcutaneous administration of low-dose IL-2 was found to be a well-tolerated and effective treatment for renal cancer. Since the combination of low doses of IL-2 and IFN has been hypothesized to have synergistic biologic and cytotoxic effects, we evaluated feasibility and patient compliance of a scheme that combined recombinant IFN-alpha (rIFN-α) (3 million units by intramuscular injection, 3 times a week) plus low-dose IL-2 (9 million IU, 3 to 5 times a week) administered subcutaneously for 2 weeks every 28 days. Results Fifteen patients with disseminated malignant melanoma previously treated with chemotherapy entered the study. All but the first 2 self-administered the therapy at home and were followed in an out-patient setting. None of them required in-patient care for toxicity. No WHO grade 4 side effects were detected; the only grade 3 side effects were fever and asthenia in 5 % of the cycles. Mild hematologic toxicity (grade 2) was observed at the highest weekly dose of IL-2. No major responses were observed in this subset of heavily pretreated patients. Conclusions We conclude that the regimen studied is feasible and well tolerated in an out-patient setting, but it is unlikely to be effective. The good patient compliance makes this schedule eligible to evaluate whether IL-2 plus rIFN-α can enhance the results of chemotherapy in this disease.

High-risk human papillomavirus in anal squamous cell carcinoma: A 'conservative' leading role

1. Unit of Gastrointestinal and Neuroendocrine Tumors, Istituto Europea di Oncologia, Milano, Lombardia, Italy; 2. Division of Pathology, Istituto Europea di Oncologia, Milano, Lombardia, Italy; 3. Unit of Viral Control of Cellular Pathways and Biology of Tumorigenesis, IFOM-IEO Campus, Milano, Lombardia, Italy; 4. Division of Radiotherapy, Istituto Europea di Oncologia, Milano, Lombardia, Italy; 5. Division of Endoscopy, Istituto Europea di Oncologia, Milano, Lombardia, Italy; 6. Division of General Surgery, Istituto Europea di Oncologia, Milano, Lombardia, Italy; 7. Division of Hepatobiliary and Pancreatic Surgery, Istituto Europea di Oncologia, Milano, Lombardia, Italy.

Institutional guidelines and ongoing studies in management of liver tumours: the experience of the European Institute of Oncology.

Background: An institutional task force on upper gastrointestinal tumours is active at the European Institute of Oncology (EIO). Members decided to collate the institutional guidelines on management of liver tumours (primary and metastatic) into a document. This article is aimed at presenting the current treatment guidelines as well as ongoing research protocols and trials in this field at the EIO. Methods: A steering committee convened to assign tasks to individual members. Contributions from experts in each treatment area were collated in a single document, in order to produce a draft for subsequent review from the aforementioned committee. Six drafts have been discussed and the final version approved. Results: Surgical, medical oncology, interventional radiology, nuclear medicine and radiation therapy approaches, their roles in management of liver tumours and ongoing research trials are presented and discussed in this article. Conclusions: At the EIO a multi-disciplinary integrated approach to liver tumours is standard and several ongoing research projects are currently active in this field.