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

4083 General Poster Session (Board #46B), Mon, 8:00 AM-12:00 PM
Interim safety results from a phase II/III trial with 5-FU, oxaliplatin, and
docetaxel (FLOT) versus epirubicin, cisplatin, and 5-FU (ECF) in patients
with locally advanced, resectable gastric/oesophagogastric junction (OGJ)
cancer: A study of the AIO. Presenting Author: Ulrike Koock, Krankenhaus
Nordwest, UCT-University Cancer Center, Frankfurt, Germany
Background: Perioperative ECF is a standard treatment for localized
gastric/OGJ adenocarcinoma. However, 5-year survival rate remain below
40%. The FLOT regime is an effective new combination with pathologic
response rates in the 15% range. This phase II/III study compares both
regimens in resectable stages. Methods: Pts are stratified by different
baseline criteria and randomized to either 3 � 3 perioperative cycles of
ECF (Epirubicin 50 mg/m2 , d1 Cisplatin 60 mg/m², d1 5-FU 200 mg/m²,
d1-d21, qd21) or 4 � 4 cycles of perioperative FLOT (Docetaxel 50mg/m2,
d1 5-FU 2600 mg/m², d1 leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m²,
d1, qd14). 5-FU can be replaced by Capecitabine in the ECF-arm (ECX).
This is a preplanned toxicity analysis after 200 pts in order to decide
whether to continue to a phase III trial. Results: 202 pts have been
randomized so far. Median age is 62 yrs; 79% of pts are male. The
Primaries were Gastric in 43.4%, OGJ in 53.2% and not evaluable/
documented in 3.4% of pts. 190 pts were eligible for the safety analyses.
Median no. of preoperative cycles was 3 and 4 with ECF/ECX and FLOT,
respectively, and 68.7% vs. 66.0% of pts (ECF/ECX vs. FLOT) started
postoperative chemotherapy (ct). Grade 3/4 side effects were observed in
52.1% of ECF/ECX and 59.6% of FLOT pts with no significant differences
between arms regarding individual grade 3/4 toxicities. Thromboembolic
events occurred in 14.5% vs. 8.5% in pts with ECF/ECX vs. FLOT (p�.25).
Serious adverse events occurred in 60.3% vs. 39.7% of pts with ECF/ECX
vs. FLOT. Preoperative delay/interruptions of ct were observed in 74.0% vs.
61.7% of pts with ECF/ECX vs. FLOT (p�.07). Dose modifications of
preoperative ct were performed in 28.1% vs. 22.3% of treatment cycles
with ECF/ECX vs. FLOT, respectively. 121 pts underwent surgery. Severe
surgical morbidity was similar in both arms (ECF/ECX, 15.8%; FLOT,
14.1%). Surgical mortality was observed in 2 and 1 pts with ECF/ECX and
FLOT. Toxic deaths were observed in 1 pt each. Conclusions: Perioperative
FLOT is feasible and safe. This supports the continuation of the trial as a
phase III.
4085 General Poster Session (Board #46D), Mon, 8:00 AM-12:00 PM
Relief of bowel-related symptoms with telotristat etiprate in octreotide
refractory carcinoid syndrome: Preliminary results of a double-blind,
placebo-controlled multicenter study. Presenting Author: Thomas M.
O’Dorisio, University of Iowa Hospitals and Clinics, Iowa City, IA
Background: Diarrhea associated with carcinoid syndrome has been attributed
to tumor production of serotonin. Telotristat etiprate, (LX1032,
LX1606), is an oral inhibitor of peripheral serotonin synthesis. This study
explored the safety, tolerability, and efficacy of telotristat etiprate in
carcinoid patients with octreotide-refractory diarrhea. Methods: Carcinoid
patients with �4 bowel movements (BMs)/day on octreotide were randomized
3:1 to receive telotristat etiprate or placebo as double-blind treatment.
Patients enrolled in sequential, escalating dose cohorts of 150, 250, 350,
or 500 mg tid, followed by a 500 mg tid expansion cohort. Patients were
followed for toxicity, 24-hr urinary 5-HIAA (u5-HIAA), BM frequency, and
self-reported bowel-related symptoms. Subjects were asked “In the past 7
days, have you had adequate relief of your carcinoid syndrome bowel
complaints such as diarrhea, urgent need to have a bowel movement,
abdominal pain or discomfort?” Responses (yes or no) were analyzed as
categorical variables. Results: 16 patients enrolled in the 4 escalating dose
cohorts and 7 in the expansion cohort; 18 on telotristat etiprate and 5 on
placebo. Median age: 62 yrs; mean 6.3 BMs/day (range, 4-10). AEs
included primarily mild-moderate diarrhea, nausea, and abdominal discomfort.
In treated subjects, adequate relief was reported as: Week 1 - 6/18
(33.3%), Week 2 - 5/16 (31.3%), Week 3 - 5/15 (33.3%), and Week 4 -
6/13 (46.0%). No placebo subjects reported improvement at any timepoint.
Biochemical response (�50%reduction in u5-HIAA) and BM response
(�30% reduction in daily BMs for 2 weeks) were associated with
reporting of adequate relief. For evaluable telotristat etiprate-treated
patients, 9/16 (56%) experienced a biochemical response and 5/18 (28%)
experienced a clinical (BM) response; no placebo subjects achieved either
biochemical or clinical response. Conclusions: Treatment with telotristat
etiprate was associated with decreases in u5-HIAA and BM frequency, and
with self-reported relief of bowel related symptoms. Treatment in an
extension phase with open-label telotristat etiprate is ongoing.
Gastrointestinal (Noncolorectal) Cancer
259s
4084 General Poster Session (Board #46C), Mon, 8:00 AM-12:00 PM
Assessment of the 7th edition of the AJCC classification and a proposal of a
new classification in patients with gastric cancer undergoing D2 gastrectomy.
Presenting Author: Vincenzo Catalano, UOC Oncologia, A. O., Pesaro,
Italy
Background: Studies on Asian, US, and German patients have moved some
criticisms on the validity of the 7th edition of the AJCC classification to
discriminate outcome of gastric cancer stages. We investigated the effect
of this AJCC classification in a high-quality surgical populations of patients
receiving D2 lymphadenectomy. Methods: From the prospective database
at San Salvatore Hospital, Pesaro, we identified 515 patientswith gastroesophageal
junction (Siewert II and III) or stomach adenocarcinoma who
underwent gastrectomy with curative intent from 1998 to 2010. Lymphadenectomy
extended to the 3rd level 12p/b nodes (D2/D3) was performed in
all patients. Overall survival (OS) probabilities, calculated from the date of
surgery to the date of death, from any cause, were estimated using the
Kaplan-Meier method and compared using the log-rank test. Results: 58%
of patients were male,median age was 73 years (range 36-96). Median
number of examined lymph nodes was 32 (range, 1-89), and only 8.9% of
patients had less than 15 examined lymph nodes; 96 patients received
adjuvant chemo- or chemoradiotherapy. As shown in the table, we proposed
a revised staging system (Pesaro Staging System, PSS), which performs
better than the 7th edition of AJCC classification in terms of survival
differences between stages. Conclusions: This study confirms once again
that the 7th edition of the AJCC classification does not discriminate
adequately the outcome from stage to stage. In a European population of
patients undergoing gastrectomy plus at least D2 lymphadenectomy, the
revised staging system, PSS, better defines patient prognosis.
7th edition AJCC Staging System Pesaro Staging System
Stage Groupings n 5-yr OS (%) p* Stage Groupings n 5-yr OS (%) p*
IA T1N0 106 86.6 I T1N0-2, T2N0 165 85.7
IB T2N0, T1N1 55 83.3 .9926 II T3-4aN0, T2N1-2 84 68.4 .0018
IIA T3N0, T2N1, T1N2 61 67.6 .0447 IIIA T3-4aN1-2 105 53.8 .044
IIB T4aN0, T3N1, T2N2, T1N3 65 64.8 .7468 IIIB TxN3, T4bNx 117 28.1 .0023
IIIA T4aN1, T3N2, T2N3 58 56.3 .3845 IV TxNxM1 44 4.6 �.0001
IIIB T4bN0-1, T4aN2, T3N3 87 35.6 .0376
IIIC T4bN2-3, T4aN3 39 8.0 .0016
IV TxNxM1 44 4.6 .0741
* Compared with row above.
4086 General Poster Session (Board #46E), Mon, 8:00 AM-12:00 PM
Association of clinical complete response (cCR) after preoperative chemoradiation
and pathological complete response (pathCR) in patients with
gastroesophageal cancer (GEC) and indispensability of trimodality therapy
(TMT). Presenting Author: Naga K Sucharita Cheedella, University of Texas
M. D. Anderson Cancer Center, Houston, TX
Background: TMT strategy has the highest level-1 evidence for treating
localized GEC. High rates of cCR (defined as post-chemoradiation negative
endoscopic biopsy and physiologic uptake on PET) are common and have
questioned the benefit from surgery in patients with cCR after chemoradiation.
We hypothesized that cCR would be associated with a high rate of
pathCR than � cCR. Methods: The data were analyzed retrospectively in
563 patients who had esophagectomy for GEC in between 2002 and 2010
at UTMDACC. Among them, 284 had TMT and post-chemoradiation
endoscopic biopsies and PET (before surgery). Multiple statistical methods
were used. Results: Of these 284 TMT patients, 218 (77%) patients
achieved a cCR. However, only 67 (31%) of 218 had a pathCR. The
sensitivity of cCR for pathCR was 97.1 % (67/69) but the specificity was
low, 29.8 % (64/215). Intriguingly, 66 patients who had � cCR, only 2
patients (3%) had a pathCR. The difference in the rate of pathCR between
the cCR and � cCR groups was significant (P � 0.001). Conclusions: Our
data show that cCR is frequent after chemoradiation but the pathCR rate is
not high and it is associated with specificity that is too low for clinical
implementation. Therefore, all TMT-eligible patients, irrespective of the
achievement of cCR or � cCR must be encouraged to undergo surgery.
Therapies that overcome chemoradiation resistance and could increase the
pathCR rate are needed for esophageal preservation in select GEC patients.
Supported by UTMDACC and generous donors.
Path CR
cCR
� -
Total
� 67 151 218
- 2 64 66
Total 69 215 284
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