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Annals of Oncology
only one course of carboplatin. We experienced grade 3 side effects in 4 patients
(vomiting, low platelets, neutropenia, deep vein thrombosis). No toxicity of higher
grade developed. Seven patients relapsed. All relapses occurred in the retroperitoneal
lymph nodes. In two patients, the retroperitoneal lymph node metastases were
discovered after the first cycle of carboplatin, so these cases are not considered real
relapses, but rather the mistake of the initial staging. To conclude, single agent
carboplatin proved to be a safe and effective treatment. The risk adapted strategy is
not consistently used in our everyday practice. We aim to improve the quality of the
initial staging to avoid false stage I assessments. We also have to promote the more
accurate pathologic examination of the specimens to be able to correctly inform the
patients on the risk of relapse and thus enable them to make a fully informed
decision on their adjuvant treatment.
Disclosure: All authors have declared no conflicts of interest.
868 PROGNOSTIC SIGNIFICANCE OF EPIDERMAL GROWTH
FACTOR RECEPTOR OVEREXPRESSION AND CHROMOSOME
7 POLYSOMY IN CLEAR CELL RENAL CELL CARCINOMA
F. Lumachi 1 , D. Santeufemia 2 , F. Pili 3 , S.M. M. Basso 4 ,G.LoRe 5 , G. Miolo 6 ,
G.B. Chiara 4 , M. Ermani 7 , S. Tumolo 2 , P. Rocca Cossu 3
1 Department of Surgical, Oncological & Gastroenterological Sciences (discog),
University of Padua, School of Medicine, Padova, ITALY, 2 Medical Oncology,
S. Maria degli Angeli Hospital, Pordenone, ITALY, 3 Department of Pathology,
University of Sassari, Sassari, ITALY, 4 Chirurgia 1, S. Maria degli Angeli Hospital,
Pordenone, ITALY, 5 Oncology, Medical Oncology, Pordenone, ITALY, 6 Centro
Riferimento Oncologico (cro), Medical Oncology, Aviano, ITALY, 7 University of
Padua, Department of Neurosciences, Padova, ITALY
Background: Clear cell renal cell carcinoma (ccRCC) is the most common
histological subtype of renal cell carcinoma. In patients with ccRCC several
prognostic markers have been suggested, enclosing epidermal growth factor receptor
(EGFR) expression and chromosome 7 polysomy (C7p). Cancer cells addicted to
EGFR bear activated mutations in the EGFR gene, and these mutations are useful in
predicting susceptibility of ccRCC to EGFR inhibitors. The aim of this study was to
evaluate the prognostic value of EGFR overexpression and C7p.
Patients and methods: Archival specimens, coupled with clinical and survival data
of 34 patients (20 men, 14 women, median age 58, range 42–79 years) who had
undergone radical nephrectomy for ccRCC were analyzed. Immunohistochemistry
and fluorescence in situ hybridization (FISH) specimens were sections of
formalin-fixed paraffin-embedded tissue. EGFR expression was detected as
membranous and cytoplasmic staining of neoplastic cells > 1%, and a ratio between
gene/centromeric signals of more than two was considered to indicate gene
amplification. Mean number of centromeric signals per nucleus was also scored to
evaluate C7p. The log-rank test was used to examine the relationship between
gender, EGFR overexpression, C7p and survival. Kaplan-Meyer analysis was
performed to compare parameters with survival.
Results: The age did not differ significantly (p = 0.79) between men and women.
Overall, the median survival was 46 months (range 5-150 months). C7p was
observed in 21 (61.8%) cases. The log-rank test showed a significantly (p = 0.01)
shorter survival among men in respect of women. We did not find any relationship
between survival and membranous (p = 0.32) or cytoplasmic (p = 0.51) EGFR
overexpression, while C7p significantly (p = 0.02) correlated with survival. Similarly,
no correlation was found (Cox’s regression) between EGFR overexpression and
survival (R = 0.41, p = 0.21), while the relationship with gender (R = 0.87, p < 0.01)
was confirmed.
Conclusions: In our preliminary study, women with ccRCC had an overall better
survival than men. EGFR was not a useful predictor of outcome, while C7p may have
a prognostic significance.
Disclosure: All authors have declared no conflicts of interest.
869 ANGIOGENIC AND SIGNALLING PROTEINS CORRELATE
RESISTANCE AND SEQUENCE OF TREATMENT IN RENAL
CELL CANCER
R. Rosa 1 , V. Damiano 1 , L. Nappi 1 , L. Formisano 1 , F. Massari 2 , A. Scarpa 3 ,
G. Martignoni 4 , R. Bianco 1 , G. Tortora 2
1 Medical Oncology, University Federico II, Napoli, ITALY, 2 Medical Oncology,
Azienda Ospedaliera Universitaria Integrata Verona-“Borgo Roma”, Verona,
ITALY, 3 Patologia e Diagnostica, Universit, Verona, ITALY, 4 Pathology and
Diagnostics, University of Verona, Verona, ITALY
Background: The multi-tyrosine kinases inhibitors and the mammalian target of
rapamycin (mTOR) inhibitors have dramatically changed the management of
metastatic renal cell carcinoma (RCC). However, a relevant issue in RCC treatment is
still the lack of a biological and molecular rationale able to establish the most
effective sequence of the different therapeutic options available.
Methods: To address this issue, we systematically assessed the effect of different
agents, alone and in sequence, on the growth, expression and secretion of key
angiogenic and signalling proteins involved in tumor growth and resistance to
treatment, in a panel of human RCC cell lines with different VHL status and in
tumors xenografted in nude mice.
Results: We demonstrated that sunitinib, sorafenib and everolimus are equally active
as single agents in inhibiting cell proliferation, signal transduction and VEGF
secretion, both in vitro and in tumors grown in mice. Pre-treatment of tumor cells
with sunitinib reduced the response to subsequent sunitinib and sorafenib but not to
everolimus. Lack by sunitinib of a persistent inhibition of key proteins including
HIF-1, VEGF and MAPK anticipates onset of resistance in xenografted tumors. After
first line sunitinib, second line everolimus was more effective than sorafenib or
sunitinib rechallenge to interfere with critical signalling proteins and VEGF and
Interleukin-8 secretion, translating into an advantage in the long-lasting inhibition of
tumor growth and significant prolongation of mice survival.
Conclusions: Our study demonstrates that angiogenic and signalling proteins predict
treatment failure with sunitinib and that the use of mTOR inhibitor everolimus in
second line is substantiated by a persistent control of proteins responsible for RCC
growth and resistance to treatment.
Disclosure: All authors have declared no conflicts of interest.
870 COMPLIANCE WITH SUNITINIB TREATMENT IN PATIENTS
WITH RENAL CELL CANCER
A. De Both 1 , V. Kruse 2 , E. De Coene 2 , N. Clottens 3 , A. Somers 3 , S. van Belle 2 ,
L. van Bortel 4 , S. Rottey 2
1 Internal Medicine, University Hospital Ghent, Ghent, BELGIUM, 2 Medical
Oncology, University Hospital Ghent, Ghent, BELGIUM, 3 Pharamcy, University
Hospital Ghent, Ghent, BELGIUM, 4 Clinical Pharamcy, University Hospital Ghent,
Ghent, BELGIUM
Introduction: Sunitinib (SUN) is one of the standard treatment options for
metastatic renal cell cancer (mRCC). There are several possible reasons for
non-compliance to the prescribed doses: oral intake of the drug, side effects and the
existence of multiple dosage forms. Prescribers are not always aware of this
non-compliance.
Methods: In Belgium SUN can only be delivered by the hospital pharmacy. This
allows calculation of the used versus the prescribed dose. Based on these data, the
minimum number of non-compliant weeks per patient were calculated.
Results: 34 incident patients were considered, treated in the Ghent University
Hospital between 2007–2012. The total number of treatment weeks for this patient
group was 1079 (ranging between 1 and 108 weeks). A total of 850 weeks were
suitable for analysis. 14 out of these 34 patients (41.2%) had at least one week in
their treatment period of non-compliance (insufficient number of pills), with the
percentage of time of treatment non-compliance in these individual patients ranging
from 2–40 % of the total treatment time, the average being 19 % of the weeks. The
group with one or more weeks of non-compliance were the patients with the longest
SUN intake: 47.2 versus 20.8 months of intake. On the other hand 5/34 patients
(14.7%) received considerably more pills from the pharmacy than their treatment
regimen warranted.
Conclusions: In our single-center database of patients treated by SUN for mRCC, we
demonstrated that over 40% of the patients were possibly non-compliant with their
prescribed SUN dose. This occurred more frequently in long-term treatment. Given
the average non-compliance time in this subgroup (19% of the weeks) we can
conclude that this might significantly influence overall survival and response to
treatment. We thus advocate a tighter patient follow-up and a control of drug
prescription and delivery, which could result in detection of non-compliance more
rapidly.
Disclosure: S. Rottey: Advisory board Pfizer, Novartis, Bayer, GSK Research grant
Pfizer, Bayer. All other authors have declared no conflicts of interest.
872 COMPARATIVE EFFICACY OF SUNITINIB VERSUS SORAFENIB
AS THE FIRST-LINE TREATMENT FOR PATIENTS WITH
METASTATIC RENAL CELL CARCINOMA
S.J. Park1 , J. Lee2 , I. Park2 , K. Park2 , J. Ahn2 , D.H. Lee2 , C. Song3 , J.H. Hong3 ,
C. Kim3 , H. Ahn3 1 2
Oncology, Asan Medical Center, Seoul, KOREA, Department of Oncology,
Asan Medical Center, University of Ulsan College of Medicine, Seoul, KOREA,
3
Department of Urology, Asan Medical Center, University of Ulsan College of
Medicine, Seoul, KOREA
Background: Sunitinib has been recommended as the primary treatment in the
patients with metastatic renal cell carcinoma (mRCC) among the vascular endothelial
growth factor tyrosine kinase inhibitor (VEGF TKI). However, there are no published
clinical data that compared directly the efficacy of targeted agents in the first line
setting. This study investigated the efficacy and toxicity of sorafenib and sunitinib as
primary treatment for patients with mRCC.
Methods: To compare the efficacy and toxicities between sorafenib and sunitinb,
clinical database was used to identify all patients with mRCC treated with VEGF
TKIs in Asan Medical Center from April 2005 to March 2011. Among 304 patients,
Volume 23 | Supplement 9 | September 2012 doi:10.1093/annonc/mds399 | ix287