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Results: 20 gastrointestinal cancer patients with cranial metastases (1.07%) were
included. The average age was 54.6 ± 1.1 years and 70% (n = 14) of the patients were
male. 20 patients cancers were as follows: 4 gastric cancer (20%), 15 colorectal cancer
( 75%) and 1 pancreas cancer (5%). 3 patients had no extracranial metastases (15%).
Lung metastases was the most common extracranial metastatic site in general, but
liver was the most solitary extracranial metastatic site. The median interval of
diagnosis-recurrence/metastases was 20.6 months (range 0-89 months) and the
median interval of diagnosis-cranial metastases was 30.1 months (range 0-138
months). Mean OS was 36.6 months in 3 patients without extracranial metastases
and 31.6 months in 17 patients with extracranial metastases.
Discussion: The most common primary sites that intend to metastasize to brain are
lung and breast. Gastrointestinal tumors rarely metastasize to cranium. Our results
were similar with literature: 0.7% of cranial metastases in gastric cancer and 1.7%
cranial metastases in colorectal cancer.The arguing site in our study were as follows:
in the literature lung was the most common site of extracranial metastases; but in our
study despite being general most common extracranial metastatic site, it was not the
solitary site of metastases. In 10 metastatic patients at the diagnosis, 5 were solely
had liver metastases without lung metastases.
Conclusion: Cranial metastases is a rare and late sign of gastrointestinal cancers. By
new approaches in diagnosis and therapy of cancer, cranial metastases is more
common. All symptomatic patients and asymptomatic patients with liver or lung
metastases may be suggested to be screened for brain.
Disclosure: All authors have declared no conflicts of interest.
661 TUMORS OF THE APPENDIX: THE EXPERIENCE OF
IPO-PORTO
T. Malheiro Sarmento1 , M.H. Abreu1 , R. Fragoso2 , M. Machado1 , N. Sousa1 ,
C. Faustino1 , P. Ferreira1 1
Medical Oncology, Portuguese Oncology Institute of Porto, Porto, PORTUGAL,
2
Medical Oncology, Instituto Portugues de Oncologia Centro do Porto, Porto,
PORTUGAL
Introduction: Malignant neoplasms of ileocecal appendix are rare, an clinical
features are unspecific, often mimicking acute appendicitis. They are diagnosed in
about 1% of appendicectomy specimens. The most common histologic types are
mucinous adenocarcinoma, intestinal-type adenocarcinoma and carcinoid tumor.
Methods: The authors reviewed the primary appendix carcinomas treated in Instituto
Português de Oncologia Francisco Gentil-Porto (IPOFG-Porto) between January
2000 and June 2011.
Results: Fourty two patients were treated during this period: 30 women (71%) and 12
men, aged between 20 and 90 years old (median age 58). Mucinous adenocarcinoma
was the most common histologic subtype, with 27 cases (64%), followed by
adenocarcinoma NOS (10 cases - 24%); carcinoids were 5 cases (12%). Fifteen percent
presented as stage IV, 7% stage III, 24% stage II and 19% stage I. The primary treatment
was surgery: 16 patients were submitted to appendicectomy, 6 patients to
appendicectomy, ooforectomy and hysterectomy, 12 to hemicolectomy. Of patients
submitted to appendicectomy, 11 (50%) had a second laparotomy in order to perform
hemicolectomy. Five percent of the patients received adjuvant chemotherapy
(mFOLFOX6). Hyperthermic Intraoperative Peritoneal Chemotherapy (HIPEC) was
performed in 18 patients with stage IV disease (peritoneal carcinomatosis). The median
follow-up was 35 months. Thirty three percent of the patients (n = 14) died because of
disease progression and 62% (n = 26) were alive with no evidence of disease.
Conclusion: Appendiceal carcinomas are rare tumours and there is limited evidence
on the indications for right hemicolectomy. The role of adjuvant chemotherapy for
adenocarcinoma of the appendix is unknown. Optimal treatment of patients with
intraperitoneal dissemination of appendiceal adenocarcinoma (mucinous peritoneal
carcinomatosis) is unclear. Selected patients treated with aggressive surgical
cytoreduction and HIPEC may have a favorable outcome in long term, but patient
selection and the experience of the treating team are critical. The benefit of systemic
chemotherapy for advanced disease is unknown.
Disclosure: All authors have declared no conflicts of interest.
662TiP PILOT STUDY OF TIGATUZUMAB (CS-1008) IN
COMBINATION WITH FOLFIRI IN PATIENTS WITH
METASTATIC COLORECTAL CANCER (CRC)
G. Kim1 , M. Borad2 , H. Pitot3 , J. Rubin3 , J. Greenberg4 , P. McCroskery4 ,
R. Beckman4 , A. Grothey3 1 2
GI Oncology, Mayo Clinic, Jacksonville, FL, UNITED STATES OF AMERICA, GI
Oncology, Mayo Clinic, Scottsdale, AZ, UNITED STATES OF AMERICA, 3 GI
Oncology, Mayo Clinic, Rochester, MN, UNITED STATES OF AMERICA,
4
Development, Daiichi Sankyo Pharma, Edison, NJ, UNITED STATES OF
AMERICA
Background: Tigatuzumab (T) is a humanized monoclonal antibody that acts as a
death receptor 5 (DR5) agonist. Preclinical studies have shown that T monotherapy
induces apoptosis in DR5-positive CRC cell lines and significantly inhibits growth in
Annals of Oncology
CRC xenograft models. T combined with FOLFIRI (folinic acid, 5-fluorouracil
(5-FU), irinotecan) has demonstrated enhancement of preclinical antitumor activity.
This pilot study assessed efficacy and safety of this combination therapy in patients
(pts) with metastatic CRC.
Methods: This was an open-label, single-arm, multicenter study of T plus FOLFIRI
in pts with histologically-confirmed metastatic CRC, an ECOG (Eastern Cooperative
Oncology Group) score ≤ 2, and adequate organ and bone marrow function. Pts were
non-homozygous for UGT1A1*28 allele. T was initially administered intravenously
(IV) at 6 mg/kg and thereafter at 2 mg/kg weekly with one treatment cycle = 4 weeks
(wks). FOLFIRI was administered IV at wks 1 and 3: irinotecan 180mg/m 2 , folinic
acid (leucovorin) 400mg/m 2 and 5-FU 400mg/m 2 bolus followed by 2400 mg/m 2
over 46-48 hours. Radiographic assessments were performed every 8 wks.
Results: Treated pts (n = 21) had a median of 3 prior therapies; 10 (48%) had prior
FOLFIRI. All pts experienced ≥1 treatment-emergent adverse event (TEAE); the
most common T-related TEAEs were fatigue (12 pts; 57%) and nausea (8 pts; 38%).
17 pts (81%) experienced a ≥ grade 3 TEAE; the most common was neutropenia (9
pts; 43%) which was partly attributed to T in 5 pts (24%). Serious AEs (SAEs)
occurred in 15 pts (71%). The most common SAE was anemia (3 pts; 14%), all
unrelated to T. There was 1 SAE of neutropenia related to T. Median progression-free
survival (PFS) was 3.7 months. 2 pts had unconfirmed partial response; 9 pts had
stable disease. The trial is ongoing.
Conclusions: T displays acceptable safety and tolerability when combined with
FOLFIRI. The observed median PFS compares favorably with historical results in 3 rd /
4 th line treated pts, but study size and single arm design preclude formal conclusions.
The SAEs reported were comparable to those reported for T in combination with
other chemotherapies.
Disclosure: J. Greenberg: Full-time employee of and stockholder in Daiichi Sankyo
Pharmaceutical Development. P. McCroskery: Full-time employee of and stockholder
in Daiichi Sankyo Pharmaceutical Development. Stockholder in Johnson & Johnson
Corporation. R. Beckman: Full-time employee of and stockholder in Daiichi Sankyo
Pharmaceutical Development. Stockholder in Johnson & Johnson Corporation. A.
Grothey: Contracted researcher for Daiichi Sankyo Pharmaceutical Development. All
other authors have declared no conflicts of interest.
663TiP AXE BEAM: ENCOURAGING EARLY RESULTS OF A
NEO-ADJUVANT BEVACIZUMAB, CAPECITABINE +/-
OXALIPLATIN AND RADIATION MULTIMODALITY REGIMEN
FOR LOCALLY ADVANCED RECTAL CANCER
G. Chiritescu 1 , K. Dumon 1 , P. Vergauwe 2 , J. Arts 3 ,A.D’Hoore 4 , A. Debucquoy 5 ,
M. Verstraete 5 , X. Sagaert 6 , K. Haustermans 5 , E. Van Cutsem 1
1 Digestive Oncology, University Hospital Leuven, Leuven, BELGIUM,
2 Gastroenterology, A.Z. Groeninge, Kortrijk, BELGIUM, 3 Gastroenterology, A.Z.
Sint Lucas, Brugge, BELGIUM, 4 Abdominal Surgery, University Hospital Leuven,
Leuven, BELGIUM, 5 Lab of Experimental Radiotherapy, Department of Radiation
Oncology, University Hospital Leuven, Leuven, BELGIUM, 6 Pathology, University
Hospital Leuven, Leuven, BELGIUM
In an academic multicentric phase II study, patients (pts) with locally advanced
rectal cancer are randomized to receive bevacizumab (5mg/kg), capecitabine
(1650mg/m 2 /day) and radiotherapy (1.8Gy/day) with (Arm A) or without (Arm B)
oxaliplatin (50mg/m 2 ). Chemoradiotherapy (CRT) starts at 2 weeks after 1 st infusion
of bevacizumab and continues for 5 weeks. Total mesorectal excision is planned at
6-8 weeks post CRT. Immunohistochemical staining to study the functionality of
blood vessels and Luminex analyses to assess the changes in circulating VEGF
ligands are performed on tissues and blood samples from consenting pts.
Pathological complete response (pCR) rate, safety profile and identification of
biomarkers for early response prediction are the main endpoints.
Results: Sixty five pts with median age 60 have been enrolled to date. Fifty seven pts
completed the full protocol scheme, with a relative dose intensity of 97% for
bevacizumab, 95% for capecitabine and 93% for oxaliplatin. Preliminary safety data
from 60 evaluable pts show that the regimen is generally well tolerated. Most severe
adverse events were post-operative (wound infections, leaks) in 9 pts, equally
distributed between arms. During CRT, grade 3 toxicities were more frequent in Arm
A: fatigue (1), diarrhea (2), infection (2), febrile neutropenia (1), sensory neuropathy
(1). Two pts deceased due to disease progression and one due to lung embolism
post-surgery. Fifty two pts are evaluable for response. pCR was seen in 11 pts, 30%
(8/26) in Arm A and 12% (3/26) in Arm B (p = 0.08). The rate of good responders
(Dworak TRG 3,4) was higher in Arm A 18/26 versus Arm B 10/26 (p = 0.05).
Changes in the pericyt coverage of the blood vessels, proliferation of the tumour cells
and plasma concentrations of PDGF-AA, PDGF-BB and VEGF were observed and
will be further assessed.
Conclusions: Chemoradiotherapy in combination with bevacizumab showed an
acceptable safety profile in this patient population. Adding oxaliplatin determined a
slight increase of toxicity but might enhance the percentage of responders. PDGF
may be a predictor of response in this setting. Further analyses are ongoing.
Conducted with support from Roche and Sanofi Aventis.
Disclosure: K. Haustermans: The author has received research funding from Roche.
E. Van Cutsem: The author has received research funding by Roche and Sanofi
Aventis. All other authors have declared no conflicts of interest.
ix222 | Abstracts Volume 23 | Supplement 9 | September 2012