A pilot study employing hepatic intra-arterial irinotecan injection of drug-eluting beads as salvage therapy in liver metastatic colorectal cancer patients without extrahepatic involvement: the first southern Italy experience.

BACKGROUND: The main aim of this prospective study was to evaluate the efficacy of drug-eluting beads with irinotecan (DEBIRI) for liver metastases from colorectal cancer. Secondary aims were to evaluate survival and toxicity. METHODS: Twenty-five patients with metastases in <50% of the liver and without extrahepatic involvement were enrolled. Treatment response assessment was performed by multidetector contrast enhancement computed tomography (MDCT) with evaluation of the enhancement pattern of the target lesion and tumor response rates according to modified Response Evaluation Criteria in Solid Tumors (mRECIST, Version 1.1). All adverse events were recorded by the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events, Version 3.0. Associations of tumor response and variables were calculated using the chi-squared test. Overall survival (OS) was calculated using the Kaplan-Meier method. Comparisons were made using the log-rank test. RESULTS: According to mRECIST, complete response (CR) was observed in 21.8% of patients, partial response (PR) in 13%, stable disease (SD) in 52.2% and progressive disease (PD) in 13% of patients. Response rate (RR = CR + PR) was 34.8%. No associations between treatment response and variables such as Dukes' classification, grading and Kras status were found (P>0.05). The median OS was 37 months (95% CI: 13.881 to 60.119). Cox regression model showed that neither site, Dukes' classification, grading, Kras status nor number of chemotherapy treatments pre-DEBIRI influenced the OS. The log-rank test showed no statistically significant difference in OS among patients who underwent 1, 2 or 3 DEBIRI treatments (χ2=2.831, P=0.09). In our study, the main toxicities included postembolization syndrome (PES), hypertransaminasemia and fever. CONCLUSION: The favorable tumor response and the favorable toxicity profile make DEBIRI treatment a potential third-line therapy. Although further larger studies are needed to confirm these data, we can state that DEBIRI is an attractive emerging treatment in these patients.

Sorafenib and locoregional deep electro-hyperthermia in advanced hepatocellular carcinoma: A phase II study.

The standard treatment for advanced hepatocellular carcinoma (HCC) is sorafenib, a multikinase inhibitor of tumor cell proliferation and angiogenesis. Hyperthermia inhibits angiogenesis and promotes apoptosis. Potential synergic antiangiogenic and proapoptotic effects represent the rationale for combining sorafenib with electro-hyperthermia (EHY) in HCC. A total of 21 patients (median age, 64 years; range, 55-73 years) with advanced HCC were enrolled in the current study between February 2009 and September 2010. EHY was achieved by arranging capacitive electrodes with a deep hypothermia radiofrequency field of 13.56 Mhz at 80 W for 60 min, three times per week for six weeks, followed by two weeks without treatment, in combination with sorafenib at a dose of 800 mg every other day. According to the modified Response Evaluation Criteria in Solid Tumors criteria, 50% achieved stable disease, 5% achieved partial response and 45% achieved progressive disease. No complete response was observed. The progression-free survival (PFS) rate at six months was 38%, while the median PFS and overall survival times were 5.2 [95% confidence interval (CI), 4.2-6.2) and 10.4 (95% CI, 10-11) months, respectively. The overall incidence of treatment-related adverse events was 80%, predominantly of grade 1 or 2. Grade 3 toxicity included fatigue, diarrhea, hand-foot skin reaction and hypertension. In the present study, the sorafenib plus EHY combination was feasible and well tolerated, and no major complications were observed. The initial findings indicated that this combination offers a promising option for advanced HCC.

Unresectable lung malignancy: combination therapy with segmental pulmonary arterial chemoembolization with drug-eluting microspheres and radiofrequency ablation in 17 patients.

PURPOSE: To evaluate the feasibility, safety, and effectiveness of combining segmental pulmonary arterial chemoembolization (SPACE) and percutaneous radiofrequency (RF) ablation in patients with unresectable lung neoplasms or patients with resectable neoplasms who refused surgery and to compare the local tumor progression (LTP) rate with that in previous studies of RF ablation alone. MATERIALS AND METHODS: After institutional review board approval and informed consent, 17 patients with primary and metastatic lung cancer were enrolled in this prospective study. Between January 2008 and February 2011, 20 nodules (median diameter, 3.0 cm; range, 2.0-5.0 cm) were treated during 19 sessions. Antineoplastic agents loaded on 50-100-µm microspheres were selectively infused into specific pulmonary arteries. Percutaneous computed tomography (CT)-guided RF ablation of lung nodules was performed 48 hours after SPACE. Follow-up consisted of enhanced CT 48 hours after combination treatment was completed, after 30 days, and every 3 months thereafter. Fluorine 18 fluorodeoxyglucose positron emission tomography was performed 3 months after combination therapy and then every 6 months. The t test was used to compare groups. RESULTS: Technical success was achieved in 100% of cases. Ventilation-lung single photon emission computed tomography showed a wide area without ventilation in the lung parenchyma treated with SPACE. The LTP rate was 21% (three of 14 nodules) in 3-5-cm-diameter tumors and 0% (zero of six nodules) in tumors of 3 cm or smaller in diameter. Complete response was achieved in 65% (11 of 17) of patients at minimum follow-up of 6 months. Overall, treatment was well tolerated. Major complications were pneumothorax in five of 19 sessions (26%) and one bronchopleural fistula (one of 19, 5%). No treatment-related changes in general lung function were noted. CONCLUSION: Combination therapy with RF ablation after SPACE to treat unresectable lung tumors is technically feasible, safe, and effective and may represent an advantage over RF ablation alone.

Single-step therapy -- feasibility and safety of simultaneous transarterial chemoembolization and radiofrequency ablation for hepatic malignancies.

BACKGROUND: Radiofrequency thermal ablation (RFA) has been demonstrated to be useful for the treatment of liver neoplasms. The study aimed to evaluate the feasibility and safety of the combination of transarterial chemoembolization (TACE) and RFA, performed simultaneously to treat primary and secondary liver neoplasms. PATIENTS AND METHODS: From July 2006 to October 2007, 34 patients (21 with HCC and 13 with liver metastases) underwent 37 sessions of treatment. The schedule consisted of: induction TACE (with epirubicin, mitomycin C and lipiodol, or with doxorubicin/irinotecan loaded on microspheres), percutaneous RFA and second TACE. Monopolar RFA was used on 52 nodules, whereas the bipolar multiprobe technique was used in 6 cases. RESULTS: The treatment was well tolerated, with moderate hepatic and hematological toxicity. In total 51 nodules were evaluable for response, with technical success in 45/51 cases (88%). CONCLUSION: Combined TACE plus RFA is feasible and safe; the preliminary data make it a promising procedure with regard to efficacy and support further investigation.

Irinotecan (CPT-11) and mitomycin-C (MMC) as second-line therapy in advanced gastric cancer: a phase II study of the Gruppo Oncologico dell' Italia Meridionale (prot. 2106).

OBJECTIVE: The aim of this study was to evaluate the activity and toxicity of a combination regimen of CPT-11 and mitomycin-c as second-line chemotherapy for pretreated patients with advanced, metastatic, or both, gastric adenocarcinoma. MATERIALS AND METHODS: Patients with pretreated metastatic disease or early relapsed after adjuvant chemotherapy were enrolled. Entry criteria included histologic/cytologic diagnosis of gastric adenocarcinoma, age 18 to 75 years, performance status > or =70 (Karnofsky scale), bi-dimensionally measurable disease. Patients received CPT-11 and mitomycin-c at the dosage of 150 mg/m2 on days 1 and 15, and 8 mg/m2 on day 1, respectively, every 4 weeks. The disease evaluation was done every 3 cycles. RESULTS: Among the 38 patients we observed, 1 (3%) complete response and 11 (29%) partial responses for an overall response rate of 32% according to an intent-to-treat analysis. The median duration of response was 6.5 months. The median time to progression was 4 months with a median overall survival 8 months. All patients were evaluable for toxicity and the only grade 3-4 observed toxicities were leukopenia (8%), neutropenia (21%), and anemia (5%). CONCLUSIONS: The combination of CPT-11 and mitomycin-c is an active and well tolerated second-line treatment in pretreated gastric cancer patients. Further studies are needed to test its role in first-line treatment.