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

368s Head and Neck Cancer
5548 General Poster Session (Board #22H), Sat, 1:15 PM-5:15 PM
Recurrent/metastatic salivary gland malignancies (RMSGM): Final report of
60 cases treated with cisplatin plus vinorelbine (DDP�VNB). Presenting
Author: Fulvia Pedani, Department of Medical Oncology, San Giovanni
Antica Sede Hospital, Turin, Italy
Background: RMSGM are not amenable to the usual treatment with surgery
and post-operative radiotherapy. The role of chemotherapy (CT) for RMSGM
is palliative only. VNB showed moderate activity in our experience (Bull
Cancer 85:892;1998) and in a randomized phase II trial we had demonstrated
that the DDP�VNB combination had a better outcome than VNB
alone (Cancer 91:541; 2001). In this abstract we report the final results of
this combination in 60 cases. Methods: From April 2001 to February 2009
, 60 cases with RMSGM were enrolled. All patients received the following
regimen: DDP 80 mg/sm d.1 � VNB 25 mg/sm d. 1,8 every 3 weeks. The
study foresees a maximum of 6 cycles. Results: Patients characteristics
were as follows: 35 males (58%) and 25 females (42%).; median age: 56
yrs (range 20-68); median ECOG PS: 1 (0-2); histology: adenocarcinoma
15 (25%), adenoid cystic ca. 34 (57%), others 11 (18%); site of disease:
local 30 (50%) , mts �/- local 30 (50%). Forty-two pts received DDP�VNB
as first line CT (70%) while 18 pts (30%) had the combination as
second-line CT (30%). After a median of 5 cycles of first line DDP�VNB
responses were: 3 CR (7%), 10 PR (24%), 14 NC (33%) and 15 PD (36%).
After a median of 4 cycles of second line CT responses were: 0 CR; 1 PR
(5%), 6 NC (33%) 11 PD (62%). Median survival: 10 months (3-29) for
first line CT ; 4 months (1-12) for second line CT. G3-4 toxicity:
neutropenia (20%), anemia (12%), nausea/vomiting (12%) , peripheral
toxicity (3%). Conclusions: DDP�VNB is an effective first line CT in
RMSGM ; second line CT has a low palliative activity. Toxicity seems
acceptable. This regimen could be suitable for an integration with new
biologic target agents.
5550 General Poster Session (Board #23B), Sat, 1:15 PM-5:15 PM
Preoperative recombinant adenoviral human p53 gene combined with
intensity-modulated radiation therapy in treatment of stage IV papillary
thyroid carcinoma: A randomized clinical study. Presenting Author: Jingqiang
Zhu, West China Hospital in Sichuan University, Chengdu, China
Background: Most of stage IV papillary thyroid carcinoma (PTC) is initially
unresectable due to invading surrounding structures, and is also commonly
resistant to standard radio- or chemo-therapy. P53 gene therapy could
increase tumor radiosensitivity and inhibit tumor angiogenesis. This study
is to evaluate the benefits of pre-operative recombinant adenoviral human
p53 gene (rAd-p53) combined with intensity-modulated radiation therapy
(IMRT) in treatment of stage IV PTC. Methods: Forty-six patients with
historically-diagnosed stage IV PTC, satisfying the inclusion criteria, were
randomly assigned into two groups: experimental group (EG) control group
(CG). EG received intratumoral injection of 2-4�1012 rAd-p53 viral
particles (VP) per 3 days for 10 times and IMRT once per day for 28 days at
a total dose of 65 Gy. CG received the same IMRT therapy. Once month
after the combined treatment, patients were assessed for resectability. A
radical surgery was performed on the patients with a resectable tumor. All
the patients received standard I131 therapy 1-1.5 months after surgery or
after the last IMRT. Results: EG including 25 cases, 19 females and 6
males, had a radical surgery rate of 76% (19/25), one-year survival rate of
96%, and no local recurrence and distant metastases for patients having a
surgery. The tumors in six patients of EG were still unresectable. But all
these six patients had a local partial response. The tissue sample analyses
showed increased fibrous tissues, apoptotic cells, and increased Bax and
p21 protein and mRNA levels. CG including 21 cases, 15 females and 6
males, had a radical surgery rate of 47.6% (10/21), one-year survival rate
of 81.0%, and distant metastatic rate of 20% (2/10) for patients having a
surgery. The local partial response rate of unresectable patients in CG was
72.7% (8/11). There were no changes in Bax and p21 protein and mRNA
levels. The main side effects of rAd-p53 were self-limited fever, occurring
in 24 of EG patients. Conclusions: Pre-perative rAd-p53 combinedwith
IMRT in treatment of the stage IV PTC increases radical surgical rate and
response rate, and improves long-term efficacy.
5549 General Poster Session (Board #23A), Sat, 1:15 PM-5:15 PM
Phase II study of temsirolimus and erlotinib in patients (pts) with
recurrent/metastatic (R/M), platinum-refractory head and neck squamous
cell carcinoma (HNSCC). Presenting Author: Julie E. Bauman, University of
New Mexico, Albuquerque, NM
Background: The Epidermal Growth Factor Receptor (EGFR) is a validated
target in HNSCC. In R/M disease, primary or acquired resistance to
anti-EGFR therapy inevitably occurs. Downstream activation of the PI3K/
Akt/mTOR pathway is an established resistance mechanism. We hypothesized
that concurrent mTOR blockade may improve efficacy of anti-EGFR
therapy and conducted this phase II study. Methods: We evaluated the
combination of erlotinib 150 mg po daily and temsirolimus 15 mg IV
weekly in pts with platinum-refractory R/M HNSCC and ECOG PS 0-2. The
exact, single-stage phase II design had 80% power (5% significance level)
to detect improvement in progression-free survival (PFS) from 2.3 to 4.4
mos with 35 evaluable pts. Correlatives included determination of PIK3CA
mutation (mut) status; p16, EGFR and PTEN expression; and immunomodulatory
cytokine levels. Results: From Dec 2009 – Mar 2011, 12 pts
enrolled. Six pts withdrew prior to first planned response assessment, due
to toxicity (5) or death (1), prompting referral to the Data Safety and
Monitoring Committee and early closure. Grade � 3 toxicities included
fatigue (5), diarrhea (2), GI infection/peritonitis (2), dyspnea (2), HN
edema (2), and neutropenia (1). Among 8 progression-evaluable pt,
median PFS was 1.9 mos. Median OS was 4.1 mos. 4/12 tumors were
p16(�); 4/10 were EGFR(�); 11/11 showed no PTEN expression. PIK3CA
mut was present in 1/11; the mut(�) pt withdrew after 3 wk for
diarrhea/peritonitis with minor response. There were no associations
between tumor p16, EGFR or PTEN status and oncologic outcomes. Five of
6 toxicity-related withdrawals occurred in p16(-) pts. Immunomodulatory
cytokine levels in pre- and post-temsirolimus plasma did not significantly
differ or associate with toxicity. Two pts with � 4.4 mos PFS were p16(-)
and PIK3CA mut(-). Conclusions: The combination of erlotinib and temsirolimus
was poorly tolerated in this population, with toxicities predominant in
p16(-) pts. Although the sample size was small, this R/M cohort demonstrated
lack of PTEN expression and 9% PIK3CA mut, justifying further
investigation of PI3K/Akt/mTOR pathway inhibitors in selected HNSCC pts.
5551 General Poster Session (Board #23C), Sat, 1:15 PM-5:15 PM
Association of smoking status with p16 and cyclin D1 (CCND1) expression
with clinical characteristics and overall survival (OS) in oropharyngeal
squamous cell carcinoma (OSC). Presenting Author: Mei-Kim Ang, National
Cancer Centre, Singapore, Singapore
Background: Smoking-related head and neck cancer (HNC) is genetically
different, with higher mutation rates compared with non-smokers (NS).
Human papillomavirus (HPV)-positive (�) OSC has a superior prognosis
independent of treatment. Among HPV� patients (pt), current or prior
smokers (CS) have poor OS compared with NS. Expression of p16, a known
HPV surrogate, and CYD1, a cell cycle marker often dysregulated in HNC,
was evaluated with respect to smoking status and OS. Methods: Expression
of p16 and CYD1 was assessed by immunohistochemistry in 108 OSC pt
treated between 1999-2009, using cutoffs of �70% (p16�) and �10%
(CYD1�) stained tumor cells. Associations between expression, clinical
characteristics and OS were evaluated by Kaplan-Meier method and
compared by log rank test. Hazard ratio (HR) for death was estimated using
Cox models. Results: 31 pt (28.7%) were p16� and 80 pt (75.5%) were
CYD1 negative(-). p16� pt were younger (median age 57 v 66 yrs,
p�0.002), more likely female (35.5% v 15.2%, p�0.035), NS (51.6% v
13.9%, p�0.001) with lower combined age-comorbidity score (ageCS)
(p�0.003). CYD1� pt were older (median 66 v 57 yrs, p�0.015), more
likely CS (81.5% v 48.1%, p�0.002) with higher ageCS (p�0.018). At a
median f/u of 65.7 months, median OS was 57.3 months. p16� pt had
better OS than p16- pt (median OS not reached (NR) v 22.3 mths,
p�0.001). CYD1� pt had poorer OS than CYD1- pt (median OS NR v 17.7
mths, p�0.001). On multivariable analysis p16 and CYD1 status were
independently associated with OS (HR 0.412, p�0.045 and HR 4.06,
p�0.011 respectively), independent of smoking status (HR 5.01,
p�0.008), ageCS (HR 1.32 per 1 point increase, p�0.001) and stage.
Strikingly, among NS, 5-year OS in p16� compared with p16- pt was
100% vs 67% (p�0.001). In contrast, among CS, p16 status had no
association with OS (HR 0.97, p�0.943), while CYD1 status and ageCS
were independent predictors of death (HR 4.70, p�0.025 and HR 1.28,
p�0.001 respectively). Conclusions: In OSC, NS with high p16 expression
have excellent prognosis. Among CS, pt with fewer comorbidities and low
CYD1 expression have better OS. p16 status was not prognostic in the latter
group of patients.
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