A randomized, multicenter, phase II study of vandetanib monotherapy versus vandetanib in combination with gemcitabine versus gemcitabine plus placebo in subjects with advanced biliary tract cancer: the VanGogh study.

BACKGROUND: The management of biliary tract cancers (BTCs) is complex due to limited data on the optimal therapeutic approach. This phase II multicenter study evaluated the efficacy and tolerability of vandetanib monotherapy compared with vandetanib plus gemcitabine or gemcitabine plus placebo in patients with advanced BTC. PATIENTS AND METHODS: Patients were randomized in a 1 : 1 : 1 ratio to three treatment groups: vandetanib 300 mg monotherapy (V), vandetanib 100 mg plus gemcitabine (V/G), gemcitabine plus placebo (G/P). Vandetanib (300 mg or 100 mg) or placebo was given in single oral daily doses. Gemcitabine 1000 mg/m(2) was i.v. infused on day 1 and day 8 of each 21-day cycle. The primary end point was progression-free survival (PFS). Secondary end points were: objective response rate (ORR), disease control rate, overall survival, duration of response, performance status and safety outcomes. RESULTS: A total of 173 patients (mean age 63.6 years) were recruited at 19 centers across Italy. Median (95% confidence intervals) PFS (days) were 105 (72-155), 114 (91-193) and 148 (71-225), respectively, for the V, V/G and G/P treatment groups, with no statistical difference among them (P = 0.18). No statistical difference between treatments was observed for secondary end points, except ORR, which slightly favored the V/G combination over other treatments. The proportion of patients reporting adverse events (AEs) was similar for the three groups (96.6% in V arm, 91.4% in the V/G arm and 89.3% in the G/P arm). CONCLUSIONS: Vandetanib treatment did not improve PFS in patients with advanced BTC. The safety profile of vandetanib did not show any additional AEs or worsening of already known AEs. CLINICAL TRIAL NUMBER: NCT00753675.

Sorafenib in patients with Child-Pugh class A and B advanced hepatocellular carcinoma: a prospective feasibility analysis.

BACKGROUND: Sorafenib has shown survival benefits in patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh (CP) class A liver function. There are few prospective data on sorafenib in patients with HCC and CP class B. PATIENTS AND METHODS: A consecutive prospective series of 300 patients with CP class A or B HCC were enrolled in a dual-phase trial to determine survival and safety data according to liver function (class A or B) in patients receiving oral sorafenib 800 mg daily. [Results of this study were presented in part at the ASCO 2012 Gastrointestinal Cancers Symposium, 19-21 January 2012. J Clin Oncol 2012; 30 (Suppl 4): abstract 306.] RESULTS: Overall progression-free survival (PFS), time to progression (TTP) and overall survival (OS) were 3.9, 4.1 and 9.1 months, respectively. For patients with CP class A versus B status, PFS was 4.3 versus 2.1 months, TTP was 4.2 versus 3.8 months and OS was 10.0 versus 3. 8 months. Extrahepatic spread was associated with worse outcomes but taken together with CP class, liver function played a greater role in reducing survival. Adverse events for the two CP groups were similar. CONCLUSION: Although patients with HCC and CP class B liver function have poorer outcomes than those with CP class A function, data suggest that patients with CP class B liver function can tolerate treatment and may still benefit from sorafenib.

UFT as maintenance therapy in patients with advanced colorectal cancer responsive to the FOLFOX4 regimen.

BACKGROUND: In advanced colorectal cancer (ACC), FOLFOX4 has been accepted as a standard chemotherapeutic regimen. Due to the neurotoxicity induced by oxaliplatin, which occurs in about 50% of patients during the 6-month FOLFOX4 regimen, and the frequent need for hospitalization, alternative regimens may be required. We aimed to determine whether a 'maintenance' therapy with oral UFT (uracil-tegafur) in patients responding to FOLFOX4 is able to maintain the response and improve the quality of life (QoL) as a result of the outpatient regimen and lower psychological distress. METHODS: Untreated patients with ACC who did not progress after 6 months of FOLFOX4 received oral UFT until disease progression or unacceptable toxicity. The aim of the study was to maintain the response obtained with the FOLFOX4 regimen for at least 6 months. The secondary objective was to evaluate QoL during the two different treatment regimens utilizing the 36-item Short Form Health Survey (SF-36). RESULTS: From January 2003 to August 2004, out of the enrolled 30 patients [22 males and 8 females; 2 patients with a complete response (CR), 14 patients with a partial response (PR) and 6 patients in stable disease (SD) after 6 months of FOLFOX4] 22 continued therapy with UFT until progression without significant toxicity; the remaining 8 patients (27%) had progressive disease (PD) during or at the end of FOLFOX4 and were treated with other regimen. After 6 months of UFT, 4 patients (13%) had CR, 6 patients (20%) PR and 4 patients (13%) SD; 16 patients (53%) progressed. Median follow-up was 31 months [interquartile range (IQR): 20-31 months]; 14 patients died of PD. The median time to progression was 13.9 (IQR: 7.7-20.1) months and the median survival time was 31 months (IQR: 20-31 months). Evaluation of QoL demonstrated a trend towards better QoL during UFT treatment. CONCLUSIONS: These results support the feasibility of maintaining good response and improving QoL (measured by SF-36) with an oral fluoropyrimidine after combination chemotherapy in ACC patients; moreover, since UFT can be used orally, patient compliance is increased and the duration of hospitalization can be decreased.

Can Stereotactic Body Radiation Therapy Be a Viable and Efficient Therapeutic Option for Unresectable Locally Advanced Pancreatic Adenocarcinoma? Results of a Phase 2 Study.

PURPOSE: To assess the efficacy of stereotactic body radiotherapy in patients with unresectable locally advanced pancreatic cancer. MATERIALS AND METHODS: All patients received a prescription dose of 45 Gy in 6 fractions. Primary end point was freedom from local progression. Secondary end points were overall survival, progression-free survival, and toxicity. Actuarial survival analysis and univariate or multivariate analysis were investigated. RESULTS: Forty-five patients were enrolled in a phase 2 trial. Median follow-up was 13.5 months. Freedom from local progression was 90% at 2 years. On univariate ( P < .03) and multivariate analyses ( P < .001), lesion size was statistically significant for freedom from local progression. Median progression-free survival and overall survival were 8 and 13 months, respectively. On multivariate analysis, tumor size ( P < .001) and freedom from local progression ( P < .002) were significantly correlated with overall survival. Thirty-two (71%) patients with locally advanced pancreatic cancer received chemotherapy before stereotactic body radiotherapy. Median overall survival from diagnosis was 19 months. Multivariate analysis showed that freedom from local progression ( P < .035), tumor diameter ( P < .002), and computed tomography before stereotactic body radiotherapy ( P < .001) were significantly correlated with overall survival from diagnosis. CONCLUSION: Stereotactic body radiotherapy is a safe and effective treatment for patients with locally advanced pancreatic cancer with no G3 toxicity or greater and could be a promising therapeutic option in multimodality treatment regimen.