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

5592 General Poster Session (Board #32B), Sat, 1:15 PM-5:15 PM
Final results of a phase II study of sorafenib in combination with
carboplatin and paclitaxel in patients with metastatic or recurrent squamous
cell cancer of the head and neck (SCCHN). Presenting Author:
George R. Blumenschein, University of Texas M. D. Anderson Cancer
Center, Houston, TX
Background: Cytotoxic chemotherapy (CT) is the current standard treatment
for metastatic/recurrent SCCHN. The prognosis for these patients (PTS) is
poor with a median progression free survival (PFS) of 4 months with CT.
Survival in PTS with SCCHN may correlate inversely with the number of
angiogenic growth factors secreted. Sorafenib is a potent inhibitor of c-Raf,
b-Raf, VEGFR-1/2/3 and PDGFR-�. To investigate the hypothesis that a
multi-targeted TKI added to chemotherapy would improve outcomes in
patients with metastatic/recurrent SCCHN, we performed a phase II trial of
paclitaxel and carboplatin and sorafenib (PCS). Methods: PTS were
required to have ECOG PS 0-1, measurable disease, controlled blood
pressure, and may have received one regimen of induction, concomitant or
adjuvant CT, but not CT for recurrent/metastatic disease. Sites of primary
disease excluded nasopharynx and paranasal sinus. Treatment consisted P
200mg/m2 and C AUC 6 intravenously on day 1 followed by S 400 mg orally
bid (days 2-19) in every 3-week cycles. Primary endpoint was PFS,
targeting median PFS of 6 months (M). Secondary endpoints include
overall survival (OS), response rate (RR), exploratory biomarkers, and
toxicity. Results: Forty-eight PTS with SCCHN were enrolled with 44 PTS
evaluable for PFS and response using RECIST. Median age: 56 years
(22-79 years), 89% male, median ECOG PS 1. Median follow-up was 24.1
M. RR was 55% (n�24), disease control rate was 84% (n�37), median
PFS was 8.51 M (95% CI: 5.98 ~ 13 months), and median OS was 22.6 M
(95% CI: 13.1 - NA months). Grade ³3 treatment related toxicities included
hand-foot syndrome (n�10), neutropenia (n�5), pain (n�6), elevated
lipase (n�4), elevated amylase (n�3), anemia (n�3), fatigue (n�2),
hypertension (n�2), neuropathy (n�2), febrile neutropenia (n�2), and
thrombocytopenia (n�2). Conclusions: The combination of PCS was well
tolerated and had encouraging activity in recurrent/metastatic SCCHN.
Blood-based and tissue biomarkers are being analyzed. Final outcomes,
toxicity, and correlative biomarker data will be reported.
5594 General Poster Session (Board #32D), Sat, 1:15 PM-5:15 PM
Long-term survival after distant metastasis in oropharyngeal carcinoma.
Presenting Author: Sean M. McBride, Harvard Radiation Oncology Program,
Boston, MA
Background: The possibility of cure after distant metastases (DM) in
oropharyngeal carcinoma (OPC) is uncertain. We conducted a retrospective
cohort study to determine outcome and factors predictive of survival after
metastasis in patients with OPC. Methods: From 2003-2010, 24 patients
definitively treated (96% with concurrent chemo-radiation) at the Massachusetts
General Hospital for OPC subsequently developed DM. At initial
diagnosis, HPV status was available in 13 patients, 12 of whom were
positive; six patients had T4 and 12 N2c-3 disease. Imaging studies
pertinent to the diagnosis of DM were re-reviewed; 83% of patients had DM
pathologically confirmed. Overall survival (OS) was defined from 1st
radiographic evidence of DM to either death or last follow-up. Cox
regression was used to evaluate factors predictive of OS after DM. Results:
Median time to DM after initial treatment was 8.25 months (range,
1.6-24). Twenty (83%) patients had isolated distant failure; of these, 6
had limited (1 lesion or 2 adjacent lesions) single-organ disease. Eighteen
(75%) had treatment after DM (83% had chemotherapy, 61% radiation,
and 33% surgery). Median survival after distant metastasis was 19.2
months. Median follow-up for survivors was 23.5 months (range, 7.9-
60.3). In multivariate analysis, limited single-organ disease (HR�0.14,
p�0.01, 95% CI 0.031, 0.67) was predictive of improved survival after
DM; T4 disease at initial diagnosis predicted for decreased OS after DM
(HR�3.9, p�0.01, 95% CI 1.31, 11.89). For patients with limited
single-organ disease, the 2-year OS was 82% compared to 32% with
extensive metastases (p � 0.006). Of the 6 patients with limited,
single-organ metastatic disease, two remained alive at 59.4 and 60.5
months without evidence of disease; both had HPV-positive tumors. One
patient had a solitary hepatic failure and received neoadjuvant chemotherapy
followed by partial hepatectomy; the other had a solitary lung
metastasis and received wedge resection followed by radiation. Conclusions:
Limited, single-organ metastatic disease predicts improved survival after
DM in OPC. Cure is possible in this group. Patients with limited,
single-organ distant disease should be considered for aggressive, local
salvage treatment.
Head and Neck Cancer
379s
5593 General Poster Session (Board #32C), Sat, 1:15 PM-5:15 PM
TPF induction chemotherapy and pathologic response for patients with
locally advanced and resectable oral squamous cell carcinoma. Presenting
Author: Lai-ping Zhong, Department of Oral and Maxillofacial Surgery,
Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University,
Shanghai, China
Background: The role of induction chemotherapy in locally advanced and
resectable oral squamous cell carcinoma has not been well issued.
Methods: A prospective, open label, parallel, and interventional randomized
control trail has been performed to evaluate the induction chemotherapy of
TPF protocol in resectable oral squamous cell carcinoma (OSCC) patients
at clinical stage III and IVA. The patients received two cycles of TPF
induction chemotherapy (75 mg/m2 docetaxel d1, 75mg/m2 cisplatin d1,
and 750mg/m2 5-fluorouracil d1-5) followed by radical surgery and
post-operative radiotherapy with a dose from 54 to 66 Gy (the experimental
group) or surgery and post-operative radiotherapy (the control group).
Post-surgical pathologic examination was performed to determine a positive
response or negative response. A positive response was defined as
absence of any tumor cells (pathologic complete response) or presence of
scattered foci of a few tumor cells (minimal residual disease with �10%
viable tumor cells). The primary endpoint is the survival rate; the secondary
endpoint is the local control and safety. This study has been approved by
institutional ethics committee at Ninth People’s Hospital, School of
Medicine, Shanghai Jiao Tong University. Survival analysis was conducted
with the Kaplan-Meier method. Results: 256 patients were enrolled in this
trail and 224 patients (111 in experiment group and 113 in control group)
finished the whole treatment protocol. After a median follow-up of 21
months (ranging 6-43 m). The pathologic positive response rate was 29.7%
(33/111), and negative response rate was 70.3% (78/111). The patients
with positive response had a better disease free survival (38.5�2.1m,
95%CI 34.4-42.6m, P�0.003) compared with those with negative response
(24.6�2.1m, 95%CI 20.6-28.7m) and control group (31.0�1.6m,
95%CI 27.9-34.1m). The toxicity of induction chemotherapy could be
tolerated. Conclusions: Pathologic positive response to TPF induction
chemotherapy could benefit the patients with locally advanced and
resectable OSCC. However, further long-term follow-up is needed to
confirm the benefit on survival and local control.
5595 General Poster Session (Board #32E), Sat, 1:15 PM-5:15 PM
Progressive increasing in the risk of second and subsequent malignant
tumors in patients with a head and neck cancer: A validation study with
SEER data. Presenting Author: Xavier Leon, Hospital Sant Pau, Barcelona,
Spain
Background: Patients with a head and neck squamous cell carcinoma
(HNSCC) index tumor have a increased risk (2-4% per year) for appearance
of a second malignant neoplasms (SMN) and higher risk for successive
malignant tumors during the follow-up. The objective of our study was to
validate this concept with data of patients included in the Surveillance
Epidemiology and End Results (SEER) program (1973-2008). Methods:
We performed a population-based cohort study of 149.328 patients with a
primary oral cavity, oropharynx, hypopharynx and larynx squamous cell
carcinoma index tumor, included in the SEER program, to analize the
actuarial survival-free of second and successive tumors. A total of 11.948
(8%) patients had one or more malignant tumors before the diagnosis of
HNSCC. Results: During the follow-up period, a total of 31.507 new SMN
appeared. There was a progressive and significant increase in the risk of
SMN. The annual hazard ratio for 2nd to 7th successive SMN was 2.3%,
2.7%, 3.9%, 5.4%, 8.9% and 19.1% annual risk respectively. Additionally
11 patients had 8th SMN. We observed a progressive increase in the
risk of appearence of new malignant tumors located in and outside the
aerodigestive tract. The increase in the risk of SMN was higher for tumors
located in the aerodigestive tract than tumors located outside aerodigestive
tract. It was a tendency towards the increase in the proportion of HNSCC
with the appearance of new tumors, with a decrease in the proportion of the
malignant tumors located in the lung and in locations outside the
aerodigestive tract. There were significant differences inthe risk of SMN
between second and third, third and fourth, fourth and fifth, and sist and
seventh tumors (p�0.0001). Conclusions: In patients with HNSCC there is
a progressive increase in the risk of appearance of successive tumors.
Previous tobacco and alcohol consumption, persistence in the exposure to
carcinogens and individual susceptibility (genetic) could play a role in the
increased risk of SMN. We have validated this concept with data from the
SEER program.
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