Annual Meeting Proceedings Part 1 - American Society of Clinical ...

4091 General Poster Session (Board #47B), Mon, 8:00 AM-12:00 PM
Neoadjuvant chemoradiotherapy with 5-fluorouracil-cisplatin combined
with cetuximab in patients with resectable locally advanced esophageal
carcinoma: A prospective phase I/II trial (FFCD-PRODIGE 3)—Preliminary
phase II results. Presenting Author: Laetitia Dahan, APHM La Timone,
Marseille, France
Background: Chemoradiotherapy (CRT) for locally advanced esophageal
cancer is based on 5FU combined with cisplatin. The anti-EGFR antibody
cetuximab increases the efficacy of RT-based regimen for patients (pts)
with cancer of the head and neck. This phase I/II trial was evaluating MTD,
safety and pathologic complete response (pCR) rate of the combination of
cetuximab with platinum-based CRT in esophageal cancer. Methods:
Inclusion criteria: squamous cell carcinoma or adenocarcinoma of the
esophagus, stage II-III, WHO PS 0-1. A radiotherapy of 45 grays (1.8
Gy/25F) was given over 5 weeks. During phase I, four patients experienced
limited toxicity to dose level 0, and treatment was desescalated to dose
level -1: weekly cetuximab (400 mg/m2 one week before start of radiotherapy
and 250 mg/m2 during radiotherapy), and 5 FU (500 mg/m2 per
day D1-D4) combined with cisplatin (40 mg/m2 D1) on week 1 and 5. Nine
pCR over 27 resections were needed to show a pCR rate�20% (��5%,
power � 90% ). Thirty three patients were included in the phase II. Results:
From 07-2007 to 01-2011, 33 pts were enrolled, 20 squamous cell
carcinoma (60.6%), 13 adenocarcinoma (39.4%), 25 (75.8%) stage III
and 8 (24.2%) stage II. Among 32 pts who received CRT, the main grade
3-4 toxicities were esophagitis (4 pts), leucopenia (1 pt), anaphylaxis
reaction (1 pt), rash (1 pt). Resection was achieved in 27 pts (25 R0)/31
who underwent surgery. Complete or near complete pathologic response
(TRG grades 1 and 2 to Mandard) was achieved respectively in 5 (18.5%)
and 6 (22.2%) pts. There were 4 deaths at 30 days post surgery. Severe
postoperative complications were pulmonary complications (8), anastomotic
stricture (4), gastric necrosis (1) and infection (7). The median
overall survival was 15.7 months [11.01-.], and the median relapse free
survival was 13.7 months [5.47-.]. Conclusions: Adding cetuximab to
preoperative chemoradiotherapy including 5FU and cisplatin did not
increase pCR. The recommended dose level of chemotherapy determined
during phase I could explain those disappointing results. We won’t initiate a
phase III trial.
4093 General Poster Session (Board #47D), Mon, 8:00 AM-12:00 PM
Randomized phase II study of preoperative concurrent chemoradiotherapy
with or without induction chemotherapy with S-1 and oxaliplatin in patients
with resectable esophageal cancer. Presenting Author: Dok Hyun Yoon,
Department of Oncology, Asan Medical Center, University of Ulsan College
of Medicine, Seoul, South Korea
Background: The value of adding induction chemotherapy (ICT) to preoperative
chemoradiotherapy followed by surgery has not been delineated well.
Methods: Patients with stage II, III or IVA (by AJCC 6th ed.) esophageal
cancer were randomly allocated to either 2 cycles of ICT (oxaliplatin 130
mg/m2 on day 1 and S-1 at 40 mg/m2 bid on days 1-14, every 3 weeks),
followed by concurrent chemoradiotherapy (CCRT) (46 Gy, 2 Gy/day with
oxaliplatin 130 mg/m2 on day 1 and 21 and S-1 30 mg/m2 bid, 5 days/week
during radiotherapy) and surgery (arm A, n�48), or the same chemoradiotherapy
followed by surgery without ICT (arm B, n�49). Primary outcome
was to compare pathologic complete response (pCR). Results: Thirty six and
35 patients underwent surgery with or without ICT, respectively. pCR rate
among those who underwent surgery was significantly lower in arm A
(30.6% vs. 54.3%, p�0.043). However, no difference in progression-free
survival (PFS) and overall survival (OS) was observed with a median
follow-up of 19.5 mo (95% CI, 19.1-22.4). Two-year PFS rate was 63.8%
in arm A and 55.2% in arm B (p�0.626) and 2-year OS rate was 70.1%
and 62.6%, respectively (p�0.515). While 47 (arm A) and 48 (arm B)
patients received at least 44 Gy of radiotherapy, relative dose intensity
(RDI) for oxaliplatin during CCRT was significantly lower in arm A vs. arm B
(92.7% � 19.6% vs. 99.7 � 1.8%, p�0.017). RDI for S1 did not
significantly differ (94.1% � 17.3% vs. 98.5% � 5.9%, p�0.095). G3/4
thrombocytopenia was significantly common in arm A (37.5% vs. 4.1%, p
�0.001), which contributed to lower RDI of oxaliplatin. Three patients in
arm A, compared to none in arm B, failed to survive for 90 days after
surgery. Conclusions: Adding this ICT to preoperative chemoradiotherapy
seems to cause lower pCR rate and higher toxicity during CCRT.
Gastrointestinal (Noncolorectal) Cancer
261s
4092 General Poster Session (Board #47C), Mon, 8:00 AM-12:00 PM
Positive association of gastric cancer surgery outcome with surgeon
specialization in a Shanghai high-volume general hospital. Presenting
Author: Zhenbin Shen, Department of General Surgery, Zhongshan Hospital,
Fudan University, Shanghai, China
Background: Numerous studies suggest positive relationship between
hospital volume and cancer treatment outcomes, the surgeon’s experience
and specialty training may also be important. This was examined in a high
volume hospital in Shanghai among patients who underwent gastric cancer
(GC) surgery. Methods: Data on consecutive patients (pts) undergoing R0 or
R1 GC resection in Zhongshan hospital between January 2003 and June
2010 were collected and analyzed. Follow-up on pts who were non-
Shanghai residents were less complete therefore excluded. Post-operative
mortality, pathologic results and survival outcome for pts treated by
surgical training, i.e., sub-specialized vs., non-specialized, were obtained.
Survival was calculated by the Kaplan-Meier method and Log-rank test was
used to determine statistical significance. To determine whether subspecialty
surgical training was an independent factor for overall survival
(OS), univariate and multivariate analyses were performed using Cox
proportional hazards regression. Results: Total 5,046 pts underwent R0 or
R1 GC resection were identified.1594 pts had complete covariate data,
survival information and were included in the study. Of them, the
sub-specialized group included 217 cases treated by 3 surgeons, while the
non-specialized group included 1377 cases treated by 52 surgeons. 5-year
cumulative OS was higher in the sub-specialized group (62.9% vs. 54.6%,
p�0.032). Multivariate analysis showed that tumor stage(p�0.001),
location of tumor (p�0.003), vascular invasion (p�0.001) and surgeon
(HR�1.54, p�0.001) were all associated with OS. The incidence of
positive margin was higher in non-specialized group (2.0% vs. 2.7%,
p�0.001) and the probability of retrieved lymph nodes less than 15 was
more in non-specialized group (25.9% vs. 7.3%, p�0.001). Postoperative
mortality was also higher in non-specialized group than in specialized
group(1.5% vs. 0.9%, p�0.001). Conclusions: In high volume general
hospital, sub-specialty training is desirable in gastric cancer surgery, the
quality of gastric cancer surgery can be further improved by sub-specialty
training leading to better treatment outcome.
4094 General Poster Session (Board #47E), Mon, 8:00 AM-12:00 PM
Multicenter phase II study combining panitumumab with chemoradiation
followed by surgery for patients with operable esophageal cancer (PACTstudy).
Presenting Author: Sil Kordes, Academic Medical Center, Amsterdam,
Netherlands
Background: A consistent finding in many studies in patients with operable
esophageal and gastro-esophageal junction cancer is that response to
preoperative therapy, particularly the absence of residual disease in the
surgical specimen, is an indicator of better disease-free and overall
survival. One of the potential strategies to improve these local effects of
preoperative chemoradiation (CRT) is the concurrent inhibition of the
epidermal growth factor receptor (EGFR). Therefore in our trial we evaluated
the pathologic response of panitumumab in combination with neoadjuvant
CRT as first line treatment of operable adenocarcinomas or squamous
cell carcinomas of the esophagus. Methods: Patients with resectable
cT1N1M0 or cT2-3N0-2M0 tumors received preoperative CRT consisting
of 3 administrations of panitumumab (6mg/kg) in weeks 1-3-5, weekly
administrations of carboplatin (AUC � 2) and paclitaxel (50 mg·m2 ) for 5
weeks and concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per
week) followed by surgery. The primary endpoint was the percentage of
pathologic complete responses (pCR). Results: From January 2010 till
December 2011, 91 patients were enrolled. 3 patients were not resected
due to the development of metastatic disease during CRT. Results of all
patients will be presented at ASCO. The majority of the 74 patients
operated thus far had T3 (85%) and node positive (77%) tumors. 21.6%
reached pCR and 13.5% had less than 10% viable tumor cells in the
resected specimen. R0-resection was achieved in 98.6%. There were 58
patients with adenocarcinoma and 11 patients with squamous cell carcinoma.
The pCR of these patients were 15.5% and 45.5%, respectively.
Main grade 3 toxicities were esophagitis, fatigue, rash and anorexia. 1
postoperative death occurred due to ischemia of the esophageal reconstruction.
Conclusions: The addition of panitumumab to chemoradiotherapy with
carboplatin and paclitaxel was feasible without increasing postoperative
mortality, but did not improve the rate of pathologic complete responses
compared to historical data.
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