Radiation pancreatic cancer

The regimes combining Orzel and capecitabine with radiation therapy have become the focus of increasing interest in the management of patients various malignancies including rectal, anal, locally advanced head and neck, esophageal, and pancreatic cancers. 

The use of 5-FU in combination with radiotherapy has shown improved survival in various malignancies including unresectable pancreatic cancer, resectable pancreatic cancer, Dukes B2 and C rectal cancer, esophageal cancer, and hepatobiliary cancer (Table 2). Similarly, 5-FU with concurrent radiation has also been used for organ preservation in different tumors involving bladder cancer, anal cancer, and laryngeal cancer (Table 3). 

Resectable pancreatic cancer GITSG Radiation alone (40 Gy) + 5-FU No adjustment treatment 21.0 moa 10.9 mo"... 

In another GITSG study, patients with locally unresectable pancreatic cancer were randomized to multidrug chemotherapy (streptozocin, CMT, and fluorouracil) or to 54 Gy of radiation plus fluorouracil followed by the same three-drug chemotherapy regimen. Overall survival for the combined chemoradiotherapy group was superior, i.e., 41% at one year vs 19% for the chemotherapy group (79). 

Robert F, Raben D, Spencer S. UFT /oral calcium folinate plus radiation in pancreatic cancer. Oncology (Huntingt) 1999 13(7 Suppl 3) 127-128. 

Kaiser MH, Ellenberg S S. Pancreatic cancer adj uvant combined radiation and chemotherapy following curative resection. Arch Surg 1985 120 899-903. 

Safran H, Moore T, IannittiD, etal. Paclitaxel and concurrent radiation for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 2001 49(5) 1275-1279. 

The rationale for combining 9-AC with irradiation was based on in vitro work with human colon and pancreatic cancer cell lines showing dose dependency for cytotoxicity and radiation sensitization and other reports that it is a potent radiation sensitizer in vivo (21). Unfortunately, this agent is not very well tolerated in man and clinical studies have been abandoned (12). Another agent is 9-nitro-camptothecin that is converted into 9-AC in vivo, which has also been shown to be active in vitro and in vivo (44,45). 

The treatment of pancreatic cancer continues to be challenging. Standard treatment with 5-FU-based regimens and radiation has resulted in 5-yr survival rates of 15-20%. In locally advanced and metastatic patients, the median survival is less than 10 mo. As such, investigators have tried to improve outcomes by incorporating novel agents like gemcitabine into therapy (Table 5). 

Gy of radiation to the pancreas was tolerable in pancreatic cancer patients with a 20% response rate in 15 evaluable patients. Three out of eight patients with a minimum of 12 mo follow up were alive (65). Based on these data, Cancer and Leukemia Group B (CALGB) conducted a phase II trial to examine the efficacy of concurrent twice-weekly Gemcitabine (40 mg/m2) and radiation (50.4 Gy) treatment regimen in patients with locally advanced pancreatic cancer. The preliminary result showed 55% of the... 

McGinn CJ, Smith DC, Szarka CE, et al. A phase I study of gemcitabine in combination with radiation therapy inpatients with localized, unresectable pancreatic cancer. Proc Am Soc Clin Oncol 1998 17 264a. 

S af ar AM, Altamiro PS, Recht A, et al. Phase I trial of gemcitabine, cisplatin and external beam radiation therapy for pancreatic cancer. Proc Am Soc Clin Oncol 1999 18 227a. 

Blackstock AW, Bernard S A, Richards F, et al. Phase I trial of twice-weekly gemcitabine and concurrent radiation in patients with advanced pancreatic cancer. JCO 1999 17 2208-2212. 

GITSG, Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Gastrointestinal Tumor Study Group. Cancer 1987 59(12) 2006-2010. 

Lawrence TS, et al. Radiosensitization of pancreatic cancer cells by 2, 2 -difluoro-2 -deoxycytidine. hit J Radiat Oncol Biol Phys 1996 34(4) 867-872. 

Order, S.E., Siegel, J.A., Principato, R., Zeiger, L.E., Johnson, E., Lang, P. et al. (1996) Selective tumor irradiation by infusional brachytherapy in nonresectable pancreatic cancer a phase I study. Int. J. Radiat. Oncol. Biol. Phys., 36, 1117-1126. 

In contrast to ILK, overexpression of the prosurvival integrin signaling mediator FAK protects leukemia cells from radiation- and chemo-induced apoptosis (Kasa-HARA et al. 2002). Silencing of FAK protein expression with siRNA mediated knockdown increases the radiosensitivity of different tumor cell lines originating from pancreatic cancer (Cordes et al. 2007), breast cancer, and colorectal cancer (McLean etaL 2005). Others have shown that human melanoma cells become more sensitive to the chemotherapeutic agent 5-fluorouracil when FAK expression is downregulated (Smith etal. 2005). 

Lawrence TS, Davis MA, LoneyTL (1996b) Fluoropyrimidine-mediated radiosensitization depends on cyclin E-depen-dent kinase activation. Cancer Res 56 3203-3206 Lawrence TS, Chang EY, Hahn TM (1996c) Radiosensitization of pancreatic cancer cells by 2, 2 -dilluoro-2 -deoxycyti-dine. Int J Radiat Oncol Biol Phys 34 867-872 Lawrence TS, Chang EY, Hahn TM, Shewach DS (1997) Delayed radiosensitization of human colon carcinoma cells after a brief exposure to 2, 2 -difluoro-2 -deoxycytidine (gemcitabine). Clin Cancer Res 3 777-782... 

The treatment options for large, unresectable tumors are still very limited or not effective. In this scenario, yttrium-90 internal radiation, just recently approved by the Food and Drug Administration (FDA), is proving to be a new and promising method for the therapy of unresectable hepatic tumors. Technically yttrium-90 internal radiation therapy is comparable to TACE, while its effect is based on the combination of microembolization plus internal irradiation by beta-radiation. Yttrium-90 internal radiation in liver and pancreatic cancer was first described by Arial (1965). Since then a reasonable number of studies have been presented (Table 8.4). 

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