Esophageal Squamous Cell Cancer Clinical Trial
Official title:
An Open-label, Randomized Phase III Trial of Cisplatin and 5-fluorouracil With or Without Panitumumab for Patients With Nonresectable, Advanced or Metastatic Esophageal Squamous Cell Cancer
More than 50% of patients with esophageal cancer have locally advanced or metastatic disease
at presentation. The use of chemotherapy for this patient group is increasing with the
intention of local and distant tumor control, improving quality of life and prolongation of
survival.
Previous data suggested not only that EGFR antibody targeted therapy may be safely combined
with cisplatin and 5-FU but also may increase the efficacy of standard cisplatin / 5-FU
regime.
In the present study, patients with nonresectable, advanced or metastatic esophageal squamous
cell cancer (ESCC) will receive chemotherapy or chemotherapy plus panitumumab every 3 weeks
until disease progression occurs.
The primary objective is to demonstrate superiority of 5-FU, Cisplatin and Panitumumab over
5-FU and Cisplatin alone in terms of overall survival in esophageal cancer.
More than 50% of patients with esophageal cancer have locally advanced or metastatic disease
at presentation. The use of chemotherapy for this patient group is increasing with the
intention of local and distant tumor control, improving quality of life and prolongation of
survival. The most frequently used agents are 5-fluorouracil, cisplatin, with or without
various anthracyclines. Cisplatin plus continuous 5-fluorouracil are the standard of care
regimens. Taxanes and anthracyclins are eligible agents for possible future studies, however
with higher incidences of toxicities and life threatening complications. Response rates for
single agents range from 15%-30%. Combination regimens usually tend to produce higher
response rates and occasionally patients achieve complete responses (0%-11%). However, with
the combination regimens, the median survival time remains clearly less than 10 months,
mostly between 4-8 months [Homs MY et al]. In comparison of different chemotherapy protocols,
there was no consistent benefit of any specific chemotherapy regimen. So far, cisplatin
combined with 5-fluorouracil is one of the approved standard regimens in esophageal cancer
world wide[Medical Research Council Oesophageal Cancer Group]. This so called three-weekly
MRC regimen has a better toxicity profile than the four weekly CF regimen given in Central
Europe with the higher Cisplatin dose[Lorenzen S et al], but less overall chemotherapy given
per 4 months.
Advances in molecular biology and new molecular technologies can possibly contribute to
improvement of response to neoadjuvant or palliative therapy in ESCC patients as well. EGFR1
blockade with platinum-based chemotherapy already significantly improved response rates as
well as the progression-free and overall survival compared to chemotherapy alone in patients
with head and neck tumors, which are also squamous cancers[Vermorken JB et al].
Even more, the Arbeitsgemeinschaft Internistische Onkologie (AIO) has performed a randomized
phase II study of the EGFR antibody cetuximab plus cisplatin/5-fluorouracil versus
cisplatin/5-fluorouracil alone in first-line metastatic ESCC[Lorenzen S et al]. For a maximum
of six 28-day cycles, patients received cisplatin 100 mg/m(2), day 1, plus 5-FU 1000 mg/m(2)
days 1-5 (CF), either alone or in combination with cetuximab (CET-CF). The primary endpoint
was tumor response. From 62 eligible patients included, 32 receiving CET-CF and 30 CF.
Cetuximab weekly did not exacerbate grade 3/4 toxicity, except for rash (6% vs 0%) and
diarrhea (16% vs 0%). The overall response rate according to RECIST criteria were 19% and 13%
and the disease control rates, were 75% and 57% for the CET-CF and CF arms, respectively.
With a median follow-up of 21.5 months, the median progression-free survival was 5.9 and 3.6
months and median overall survival 9.5 and 5.5 months for CET-CF and CF, respectively. No
KRAS codon 12/13 tumor mutations were identified in the 37 evaluated samples.
Thus, with respect to the AIO data and in concordance with the head and neck data by
Vermorken, EGFR antibody targeted therapy may not only be safely combined with CF, but may
also very likely increase the efficacy of standard CF, particularly with regard to a chosen
primary endpoint of overall survival. Therefore, the aim of this study is to investigate if
the overall survival of patients with squamous cell carcinoma of the esophagus can be
prolonged if panitumumab is added to the standard CF chemotherapy.
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