SCIENTIFIC REPORT 2010 - 2011 - IOV

sequence of treatments and the role of radiotherapy in both
diseases are still unclear.
ITACA-S 2: comparison of the efficacy of pre-operative
versus post-operative chemotherapy (CHT) in patients with
resectable gastric cancer (GC).
The role of adjuvant therapy in GC has been extensively
studied during the past three decades in an attempt to improve
the prognosis of patients who have undergone curative surgery.
Metanalyses of some of these trials found that post-operative
CHT led to marginal but statistically significant reductions in
mortality compared to surgery alone. Neo-adjuvant CHT has
recently received increasing attention in an attempt to improve
the rate of complete tumor resection, to combat systemic
metastases, and to prolong survival in patients with GC.
Data from randomized, controlled, prospective trials comparing
the two strategies are as yet not available. This Italian, multicentre,
open-label, randomized, superiority, phase III trial enrolls patients
with histologically confirmed, localized, resectable GC to compare
the efficacy in terms of OS of a pre-operative vs. a post-operative
CHT treatment.
Randomized phase II-III study on pre-operative or
post-operative chemotherapy in resectable pancreatic
adenocarcinoma.
Pancreatic tumor is the fourth leading cause of death in cancer
patients. Only 10-20% of patients is amenable to surgery with
a curative intent, and 5-yr survival is about 1-4%. Some phase
III trials demonstrated a benefit of post-operative adjuvant
chemotherapy vs. surgery alone in radically resected patients,
but no data from randomized clinical trials on the role of neoadjuvant
therapy are available. Some phase II studies suggest
that a pre-operative treatment could increase the rate of patients
operated with tumor-free margins and negative lymphnodes
without affecting surgery morbidity and mortality.
To evaluate the impact of a pre-operative CHT vs. a postoperative
CHT, a multicentre national phase III trial has been
recently launched. The primary objective is to compare the diseasefree
survival in patients affected by resectable pancreatic cancer
treated with pre-operative polychemotherapy (PEXG), postoperative
PEXG or post-operative monotherapy (gemcitabine).
C. NEw TarGETED DruG DEvElOpmENT
Inhibition of angiogenesis is considered as a promising
approach to the treatment of cancer. Disabling the function of
THE DEPARTMENTS - DEPARTMENT OF CLINICAL ONCOLOGY
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the vascular endothelial growth factor receptor-2 (VEGFR-2)
signaling pathway via a number of approaches, including anti-
VEGF antibodies, anti-VEGFR-2 antibodies, and small molecule
tyrosine kinase inhibitors (TKI), has been shown to inhibit new
blood vessel formation and tumor growth in a variety of animal
models. Ramucirumab is a recombinant human monoclonal
antibody that specifically binds to the extracellular domain of
VEGFR-2 with high affinity. Phase I studies and initial Phase II
studies investigating Ramucirumab have provided information
regarding safety and tolerability at clinically relevant doses, with
preliminary evidence of clinical efficacy in a variety of human
cancers. The drug is now undergoing Phase III studies in secondline
treatment of multiple diseases.
A randomized, double-blind, multicenter phase III study
of irinotecan, folinic acid, and 5-fluorouracil (FOLFIRI)
plus Ramucirumab or placebo in patients with metastatic
colorectal carcinoma progressive during or following first-line
combination therapy with bevacizumab, oxaliplatin, and a
fluoropyrimidine
This is a multicenter, randomized, double-blind, placebocontrolled
phase III trial in which patients with metastatic
colorectal cancer progressing to first-line combination therapy
with bevacizumab, oxaliplatin, and a fluoropyrimidine will be
randomized to receive either FOLFIRI plus placebo or FOLFIRI
plus Ramucirumab. Approximately 1050 patients will be
randomized to observe 756 events. The primary objective of this
study is to compare overall survival; secondary objectives are to
compare progression-free survival, objective response rate, patientreported
outcome measures, safety profile, assessment of the
association between biomarkers and clinical outcome, assessment
of anti-Ramucirumab antibodies and assessment of serum levels
of Ramucirumab.
A randomized, multicenter, double-blind, placebo-controlled
phase III study of weekly paclitaxel with or without
Ramucirumab in patients with metastatic GC, refractory
to or progressive after first-line therapy with platinum and
fluoropyrimidine.
To date, no randomized controlled trials have established a
standard second-line treatment regimen for GC after failure of a
cisplatin/fluoropyrimidine-containing regimen. At present, there
is no evidence that any given single agent or combination therapy
is clearly superior to other agents/regimens in terms of efficacy.
This is a multicenter, randomized study evaluating the efficacy