New Tools And Novel Approaches In Treating Locally Advanced Pancreatic Adenocarcinoma
Pancreatic adenocarcinoma is one of the most aggressive malignant tumors and represents the fourth leading cause of cancer-related death. The median survival of locally advanced pancreatic carcinoma is ten to thirteen months. In this year’s American Society of Clinical Oncology (ASCO) Annual Meeting, several studies were presented with novel approaches towards treating locally advanced pancreatic cancer. Wild et al. (Abstract #4055) explored a novel tool of selective delivery of TNF-alpha intratumoral injection. This approach limited the systemic toxicity, and suggested survival benefit in only the subgroup of patients with locally advanced pancreatic adenocarcinoma with stage T1-T3. Two studies were presented which were designed to assess the use of two novel agents, targeting signaling pathways, in addition to gemcitabine. Van Laethem et al. (Abstract #4050) are testing the MEK inhibitor, BAY 86-9766 in combination with gemcitabine. However, treatment related toxicity is still of concern. In the other study, Evans et al. (Abstract #TPS4134) are testing the combination of dasatinib and gemcitabine. This is a placebo-controlled, randomized, double blind phase II study. However, results are not available. Stereotactic body radiotherapy (SBRT) is an emerging technology with the comparative efficacy of single fraction radiotherapy (as is used in radiosurgery) vs. fractionated SBRT still unknown. Herman et al. (Abstract #4045) examined the role of fractionated SBRT in locally advanced pancreatic cancer. The phase II results showed a median overall survival of 15.9 months, suggesting that SBRT may be an emerging tool in the multi-modality treatment of locally advanced pancreatic cancer.
Image: The principal teaching hospital for Tufts University School of Medicine. Boston, MA, USA.
Epelbaum R, Rosenblatt E, Nasrallah S, Faraggi D, Gaitini D, Mizrahi S, Kuten A. Phase II study of gemcitabine combined with radiation therapy in patients with localized, unresectable pancreatic cancer. J SurgOncol. 2002 Nov;81(3):138-43.
Wild AT, Laheru D, Wang H, Chang KJ, Taylor GE, Donehower RC, et al. A randomized phase III multi-institutional study of TNFerade biologic with 5-FU and radiotherapy for locally advanced pancreatic cancer: Final results J Clin Oncol 2012; 30(Suppl):Abstract 4055.
Evans TRJ, Van Cutsem E, Moore MJ, Purvis JD, Strauss LC, Rock EP, et al. Dasatinib combined with gemcitabine (Gem) in patients (pts) with locally advanced pancreatic adenocarcinoma (PaCa): Design of CA180-375, a placebo-controlled, randomized, double-blind phase II trial. J Clin Oncol 2012; 30(Suppl):Abstract TPS4134 .
Van Laethem JL, Heinemann V, Martens UM, Jassem J, Michl P, Peeters M, et al. A phase I/II study of the MEK inhibitor BAY 86-9766 (BAY) in combination with gemcitabine (GEM) in patients with nonresectable, locally advanced or metastatic pancreatic cancer (PC): Phase I dose-escalation results. J Clin Oncol 2012; 30(Suppl):Abstract 4050.
Herman JM, Chang DT, Goodman KA, AWild AT, Laheru D, Zheng L, et al. A phase II multi-institutional study to evaluate gemcitabine and fractionated stereotactic body radiotherapy for unresectable, locally advanced pancreatic adenocarcinoma. J Clin Oncol 2012; 30(Suppl):Abstract 4045.
Timmerman R, Paulus R, Galvin J, et al. Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA. 2010 Mar 17;303(11):1070-6.
Schellenberg D, Goodman KA, Lee F, et al. Gemcitabine chemotherapy and single-fraction stereotactic body radiotherapy forlocally advanced pancreatic cancer. Int J RadiatOncolBiol Phys. 2008 Nov 1;72(3):678-86.
vanHorssen R, Ten Hagen TL, Eggermont AM. TNF-alpha in cancer treatment: molecular insights, antitumor effects, and clinical utility. Oncologist. 2006;11:397–408
Locksley RM, Killeen N, Lenardo MJ. The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell. 2001;104:487–501.
Jones AL, O'Brien ME, Lorentzos A, Viner C, Hanrahan A, Moore J, Millar JL, Gore ME. A randomised phase II study of carmustine alone or in combination with tumour necrosis factor in patients with advanced melanoma. Cancer ChemotherPharmacol. 1992;30:73–76
Hoshino R., Chatani Y., Yamori T., Tsuruo T., Oka H., Yoshida O., Shimada Y., Ari-i S., Wada H., Fujimoto J., Kohno M., Oncogene, 18, 813—822 (1999).
Almoguera C, Shibata D, Forrester K, et al. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 1988;53:549–554.
Khoury HJ, Guilhot F, Hughes TP, et al. Dasatinib treatment for Philadelphia chromosome-positive leukemias: practical considerations. Cancer 2009;115:1381–1394.
Uronis HE, Bullock K, Blobe G, Hsu S, Morse M, Nixon A, et al. A phase I study of gemcitabine plus dasatinib (GD) or gemcitabine plus dasatinib plus cetuximab (GDC) in refractory solid tumors. J Clin Oncol 2009; 27(Suppl):Abstract e15506.
Copyright (c) 2014 Wesam B Ahmed, John Ng, David E Wazer, Muhammad Wasif Saif
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