Cancer Treatment Today » Hepatobiliary

Chemoembolization – pro

M Levin, MD — Thu, 30 Aug 2012 02:49:30 +0000

Lay Summary: TACE is often used for hepatocellular carcinoma and neuroendocrine cancers of the liver.

This technique takes advantage of the fact that HCC is a very vascular (contains many blood vessels) tumor and gets its blood supply exclusively from the branches of the hepatic artery. This procedure is similar to intra-arterial infusion of chemotherapy. But in TACE, there is the additional step of blocking (embolizing) the small blood vessels with different types of compounds, such as gelfoam or even small metal coils. Thus, TACE has the advantages of exposing the tumor to high concentrations of chemotherapy and confining the agents locally since they are not carried away by the blood stream. At the same time, this technique deprives the tumor of its needed blood supply, which can result in the damage or death of the tumor cells.There is no established standard protocol for TACE.If the procedure is successful (>50% lipiodol uptake in necrotic tumor demonstrated on the postprocedural CT scan), the embolization is repeated in 6-8 weeks. If the lipiodol uptake is less than 50%, the authors repeat the CT scan in 6-8 weeks. If the size of the tumor is reduced, repeat TACE may be considered.The second TACE treatment should first be performed in previously untreated tumors.The third treatment completes a normal course, but further treatments are performed in patients with residual disease.

The type and frequency of complications of TACE and intra-arterial chemotherapy are similar. The potential disadvantage of TACE is that blocking the feeding vessels to the tumor(s) may make future attempts at intra-arterial infusions impossible. Moreover, so far, there are no head-to-head studies directly comparing the effectiveness of intra-arterial infusion versus chemoembolization. Studies in Japan have shown that TACE can downstage HCC. In other words, the tumors shrank enough to lower (improve) the stage of the cancer. From the practical point of view, shrinking the tumor creates the option for surgery in some of these patients. Otherwise, these patients had tumors that were not operable (eligible for operation) because of the initial large size of their tumors. More importantly, these same studies showed an improvement in survival in patients whose tumors became considerably smaller. In the U.S., trials are underway to see whether doing TACE before liver transplantation increases patient survival as compared to liver transplantation without TACE.

It is safe to say that TACE or intra-arterial chemoinfusion are palliative treatment options for HCC. However, they are not curative (Fewer than 50% of patients will have some shrinkage in tumor size. Further, they can be used only in patients with relatively preserved liver function. Several randomized trials have established this procedure as standard of care for hepatocellular cacrinoma and neuroendocrine carcinoma.

There is little evidence on what drugs are best. Studies of mitomycin of adriamycin are most common but many radiologists add ethidiol based on a comparative study, of Gelfoam and some also use cisplatin, also based on a study. Combination of four drugs are often used, without much data. Another unanswered question under study is whether to combine TACE with chemotherapy or Nexavar.

Bercin Tarlan, Hayyam Kiratli, Current Treatment of Choroidal Melanoma, Expert Rev Ophthalmol. 2012;7(2):189-19

Blue Cross Blue Shield Association, Transcatheter Arterial Chemoembolization of Hepatic Tumors. TEC Assessment, March 2001; (15): 22.

EVIDENCE-BASED PRACTICE:
Calogero Cammà, Filippo Schepis, Ambrogio Orlando, Maddalena Albanese, Lillian Shahied, Franco Trevisani, Pietro Andreone, Antonio Craxì, and Mario Cottone
Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma: Meta-Analysis of Randomized Controlled Trials
Radiology, Jul 2002; 224: 47 – 54.

NCCN, melanoma, 2013

Gemcitabine Taxotere and Xeloda (GTX) for pancreatic cancer – pro

M Levin, MD — Thu, 30 Aug 2012 02:47:12 +0000

GTX is a promising regimen for pancreatic cancer but still not adequately supported.

Current treatment options for pancreatic cancer include surgery, radiation, and chemotherapy. Although single-agent chemotherapy with gemcitabine has been a standard treatment for pancreatic cancer, research has increasingly focused on the development of combination regimens. Recently, the U.S. Food and Drug Administration approved the combination of the targeted therapy Tarceva ® (erlotinib) and gemcitabine for the treatment of locally advanced, inoperable, or metastatic pancreatic cancer.

Xeloda is an oral chemotherapy drug that belongs to a class of drugs called antimetabolites. According to researchers from Europe, the addition of the drug Xeloda (capecitabine) to Gemzar (gemcitabine) improves the duration of survival in patients with advanced stage pancreatic cancer. These results were presented at the 2005 annual meeting of the American Society of Clinical Oncology. Researchers from Austria evaluated the effects of Gemzar® with or without Xeloda® in 83 patients with metastatic pancreatic cancer. 3 Forty-two patients received bi-weekly Gemzar® (2200 mg per square meter as a 30 min. infusion) and 41 patients received the same GemzarÒ dose and schedule plus oral Xeloda® at a dose of 2500 mg per square meter from days 1 to 7. The PR rate was 14 % for the Gemzar® alone group and 17% for the Gemzar® plus Xeloda® group. Stable disease was observed in 43% of Gemzar® alone patients and 56% of the combined group. Median survival was 4 months for the Gemzar® group and 5.1 months for the Xeloda® group, with overall survivals of 8.2 and 9.5 months, respectively. Using a clinical benefit scale, there was clinical benefit for 33% of patients receiving Gemzar® alone and 48.3% for those receiving Gemzar® and Xeloda®. The toxicities of the two regimens appeared to be equivalent and these investigators were enthusiastic about this drug combination. However, there was no improvement in objective or subjective response. It was speculated that the number of patients studied was too small, possibly the dosage was suboptimal and possibly these agents are not really additive or synergistic.

The Hoosier Oncology Group evaluated a regimen of Gemzar® and Taxotere®. The response rate was 24%, with a median duration of response of 16 weeks. Thirty-five percent of patients had stable disease. The one-year survival was 27.3% and toxicity appeared to be acceptable. German researchers also evaluated the combination of Gemzar® and Taxotere® for the treatment of patients with advanced pancreatic cancer. 6 They observed a 24% response rate, with 3% (one patient) achieving a CR. The median survival was 9 months and toxicity was mild to moderate. The EORTC-GI Group compared a regimen of Taxotere® and Gemzar® to a regimen of Taxetore® and Platinol® for the treatment of advanced or metastatic (80%) pancreatic cancer. This was a randomized trial, with 49 patients receiving Taxotere® and Gemzar® and 47 receiving Taxotere® and Platinol®. Six cycles of treatment were administered to 44% of patients, with 29% receiving more than 6 cycles. The Gemzar®/Taxotere® arm was associated with low platelets and edema, while the Taxotere®/Platinol® arm had more neutropenia. The response rate was 15.8% for the Gemzar®/Taxotere® arm and 16.1% for the Taxotere®/Platinol® arm. The median survival was 7.4 months for Gemzar®/Taxotere® and 6.3 months for the Taxotere®/Platinol®. There were 11 patients alive in the Gemzar®/Taxotere® arm and 9 in the Taxotere®/Platinol® arm. They concluded that the Gemzar®/Taxotere® arm had more manageable toxicity and possibly better activity. They will be performing a randomized phase III trial to confirm these results.

Although both Xeloda and Gemcitabine/Taxotere have phase II (and for the latter phase III) trial support, putting all three together is investigational. Preliminary work was done and is ongoing at Columbia University by Dr. Fine. Combining Gemzar with Taxotere® (docetaxel) and Xeloda® (capecitabine, the oral drug that metabolizes into 5-FU within tumor cells) shows intriguing signs of efficacy. Xeloda supresses DNA replication needed for tumor growth in a different way than do Gemzar, and Taxotere backs up the cell’s structural proteins. Together, the “GTX” drugs, as they are known, may be synergistic in their antitumor effects.

In a pilot study, GTX combination was administered to 44 patients with advanced pancreatic cancer. A “partial response was observed in the liver metastases of 15 of 32 patients. Liver metastases disappeared on CT and MRI scans in three of the original 15 patients when the GTX regimen was continued for a total of eight to nine cycles. Another 28% of patients had minor response to GTX or stable disease in their liver tumors. Tumors in 12 other subjects were initially inoperable but hadn’t spread to the liver. After drug treatment and radiation, eight of these patients could undergo successful Whipple surgery for cure. For patients who failed GTX and received alternating GX-T chemotherapy, a 30% response rate and 40% stable disease rate was seen. Thus, a triple drug regimen of Xeloda, Gemzar, and Taxotere® (docetaxel) produced a 47% response rate (9% complete response rate) in 32 patients with liver metastases, which may represent an improvement over monotherapy. GTX had been rapidly adopted and a number of phase II studies have been reported, including and especially from Dr. Fine’s group but not recommended by guidelines at this point. For example, it is not mentioned by NCCN. The phase II studies have so far been reported in abstract form and not peer-reviewed except for the one by Katopodis. Partial response was observed in three (9.7%) patients, stable disease in seven (22.6%) (disease control rate: 32.3%, 95% CI: 15.80–48.71%) and disease progression in 21 (67.6%). The median progression-free survival (PFS) was 2.4 months (95% CI: 1.6–3.13) and the median overall survival (OS) was 6.3 months (95% CI: 3.38–9.23); the estimated 1-year survival rate was 14.7%. Grade III/IV neutropenia occurred in 10 (32.2%) patients and febrile neutropenia in one patient. Other severe non-hematologic toxicities were mild and manageable. After 2 chemotherapy cycles, pain control occurred in 20% of patients and stabilization of body weight in 40%.
Katopodis, Ourania (2010) Second-line chemotherapy with Capecitabine (Xeloda) and Docetaxel (Taxotere) in previously treated, unresectable adenocarcinoma of pancreas: the final results of a phase II trial. Cancer Chemotherapy and Pharmacology

Lutz MP, Ducreux M, Wagener T, et al, Docetaxel/gemcitabine or docetaxel/cisplatin in advanced pancreatic carcinoma: a randomized phase II study of the EORTC-GI group. Proceedings of the American Society of Clinical Oncology 2002;21:125a, abstract 498

Scheithauer W, Schüll B, Ulrich-Pur H, et al, Gemcitabine alone or in combination with capecitabine in patients with advanced pancreatic adenocarcinoma. Proceedings of the American Society of Clinical Oncology;21:126a, abstract number 500

Schneider BP, Ganjoo KN, Seitz DE, et al, Phase II study of gemcitabine and docetaxel in combination for advanced pancreatic cancer – a Hoosier Oncology Group study. Proceedings of the American Society of Clinical Oncology 2002; 21:137a, abstract number 546

Schmidt C, Fahlke J, Kettner E, et al, Phase II multicenter study of gemcitabine and docetaxel in patients with inoperable or metastatic pancreatic cancer. Proceedings of the American Society of Clinical Oncology 2002;21:145a, abstract number 5779.

Fine RL, Fogelman DR, Sherman W, et al. The GTX regimen: A biochemically synergistic combination for advanced pancreatic cancer (PC). Proceedings from the 39th Annual Meeting of the American Society of Clinical Oncology. Chicago IL. 2003; Abstract #112 Moore M, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a Phase III trial of the National Cancer Institute of Canada Clinical Trials Group. Journal of Clinical Oncology [early online publication]. April 23, 2007.

Fine RL, Fogelman DR, Schreibman SM, Desai M, Sherman W, Strauss J, Guba S, Andrade R, Chabot J. The gemcitabine, docetaxel, and capecitabine (GTX) regimen for metastatic pancreatic cancer: a retrospective analysis.Cancer Chemother Pharmacol. 2008 Jan;61(1):167-75

R. L. Fine, G. Moorer, W. Sherman, K. Chu, M. Maurer, J. Chabot, I. Postolov, J. Prowda, S. Schreibman, J. Levitz. Phase II trial of GTX chemotherapy in metastatic pancreatic cancer. 2009 ASCO Annual Meeting abstract 4623.

De Jesus-Acosta A, Oliver GR, Blackford A, Kinsman K, Flores EI, Wilfong LS, Zheng L, Donehower RC, Cosgrove D, Laheru D, Le DT, Chung K, Diaz LA Jr. A multicenter analysis of GTX chemotherapy in patients with locally advanced and metastatic pancreatic adenocarcinoma. Cancer Chemother Pharmacol. 2012 Feb;69(2):415-24. Epub 2011 Jul 29. link to original article contains verified protocol–with error as noted above PubMed

PTK787 for pancreat cancer – pro

M Levin, MD — Thu, 30 Aug 2012 02:43:36 +0000

PTK 787 is a selective inhibitor of all three types of the VEGF receptors. It has been shown to reduce the number of tumor microvessels with resultant dilation of the remaining vessels. It has also been shown to inhibit VEGF receptors and has been effective in animal tumor models. In addition, dynamic contrast-enhanced MRI (DCE-MRI) and PET imaging have shown a reduction in blood flow to tumors after the administration of PTK 787.

A phase 1 study of the VEGF-receptor tyrosine kinase inhibitor vatalanib (PTK787/Z 222584) and gemcitabine in patients with advanced pancreatic cancer was conducted at Stanford University. All patients received vatalanib 1250 mg daily; gemcitabine was escalated from 700 mg/m2 to 850 mg/m2 to a maximum of 1000 mg/m2. To date, 32 cycles have been given to 8 patients with pancreatic cancer, with a median of 4 cycles per patient. Only 1 patient, in the first cohort, experienced dose-limiting toxicity (DLT), with grade 3 diarrhea and hypokalemia and grade 4 neutropenia occurring simultaneously and treated without sequelae. The remaining patients in this and the next cohort (850 mg/m2) have not experienced DLT. Beyond the first cycle, grade 3 toxicities included neutropenia (1), anemia (2), thromobocytopenia (1), hypertension (2), diarrhea (1), hypokalemia (1), thrombosis (1), and proteinuria (1). Two of 8 patients had stable disease as the best response by RECIST. The remaining patients had stable disease as the best response from 2 to 6 months. No disease progression was seen at or before the first evaluation with computed tomography. No unexpected toxicities have been observed. Accrual to higher-dose gemcitabine cohorts continues. A phse II study of PTJ787alone is also ongoing.

http://clinicaltrials.gov/ct/show/NCT00226005?order=1

Kuo T, Fitzgerald A, Kaiser H, Sikic BI, Fisher GA. A phase I study of the VEGF receptor tyrosine kinase inhibitor vatalanib (PTK787/ZK 222584) and gemcitabine in patients with advanced pancreatic cancer. Program and abstracts of the 2006 Gastrointestinal Cancers Symposium; January 26-28, 2006; San Francisco, California. Abstract 127.

NCCN.ORG, Pancreatic

Radiofrequency ablation for the liver – pro

M Levin, MD — Thu, 30 Aug 2012 02:41:56 +0000

A R Gillams
Liver ablation therapy
Br. J. Radiol., September 1, 2004; 77(921): 713 – 723.

P. Liang, B. Dong, X. Yu, Y. Yang, D. Yu, L. Su, Q. Xiao, and L. Sheng
Prognostic Factors for Percutaneous Microwave Coagulation Therapy of Hepatic Metastases
Am. J. Roentgenol., November 1, 2003; 181(5): 1319 – 1325.

http://www.nice.org.uk/nicemedia/pdf/ip/IPG092guidance.pdf

NCCN, 2013: Hepatocellular adn Neuroendocrine cancer

Xeloda for hepatocellular cancer – pro

M Levin, MD — Thu, 30 Aug 2012 02:40:06 +0000

Metastatic hepatocellular carcinoma (HCC) is a difficult problem to treat. Nexavar has recently been FDA approved for HCC. Among other options are older drugs, such as capecitabine (Xeloda). A pilot study showed that capecitabine (1000 mg/m2 twice daily for 14 days every 21 days) achieved a response rate of 19% in patients with advanced biliary cancer . A larger review showed that at 2,000 mg/m2/d, capecitabine produced a 50% response rate and up to a 70% 1-year overall survival rate in hepatobiliary cancer patients. A phase II trial of gemcitabine and capecitabine in patients with unresectable or metastatic cholangiocarcinoma is being conducted by the Southwest Oncology Group (SWOG). The starting dose of capecitabine is 650 mg/m2 bid, which is subsequently reduced to 162 mg/m2, based on toxicity and renal function. The starting dose of gemcitabine is 1,000 mg/m2, which is reduced to 250 mg/m2. There as well trials of Xeloda with cisplatin and oxaliplatin, Avastin and other drugs. Xeloda requires more study singly or in combination.

Lozano R, Patt Y, Hassan M et al. Oral capecitabine (Xeloda) for the treatment of hepatobiliary cancers (hepatocellular carcinoma, cholangiocarcinoma, and gall-bladder cancer). Proc Am Soc Clin Oncol 2000; 19: 264a (Abstr 1025).

YUN YEN, MD et al, Gallbladder and Biliary Tract Carcinoma: A Comprehensive Update, Part 2 Oncology. Vol. 18 No. 8 July 1, 2004

Knox JJ, Hedley D, Oza A: Phase II trial of gemcitabine plus capecitabine in patients with advanced or metastatic adenocarcinoma of the biliary tract (abstract). Proc Am Soc Clin Oncol 22: 313, 1274, 2003.

T. W. Kim , H. M. Chang , H. J. Kang , J. R. Lee , M. H. Ryu , J. H. Ahn , J. H. Kim , J. S. Lee , and Y. K. Kang Phase II study of capecitabine plus cisplatin as first-line chemotherapy in advanced biliary cancer Ann Oncol 14: 1115-1120.

C Hsu etal, Efficacy and tolerability of bevacizumab plus capecitabine as first-line therapy in patients with advanced hepatocellular carcinoma. British Journal of Cancer 102, 981-986 (16 March 2010)

Rose, M. G., Yen, Y., So, S., Saif, M. W., Chu, E., Liu, S., Jiang, Z., Foo, A., Tilton, R., Cheng, Y.
Phase I/II study of PHY906/capecitabine in hepatocellular carcinoma
J Clin Oncol (Meeting Abstracts) 2007 25: 15152

Cryosurgical ablation of hepatocullular carcinoma – pro

M Levin, MD — Thu, 30 Aug 2012 02:36:53 +0000

Cryosurgical ablation, or cryosurgery, involves freezing of target tissues, usually by inserting a probe into the tumor through which coolant is circulated. Cryosurgery may be performed as an open surgical technique or as a closed procedure under laparoscopic or ultrasound guidance. National Comprehensive Cancer Network (NCCN, 2007) hepatocellular carcinoma guidelines state that microwave ablation, cryotherapy, radiofrequency ablation, and percutaneous ethanol injection may be used in the treatment of unresectable nonmetastatic hepatocellular carcinoma, for patients with nonmetastatic hepatocellular carcinoma who do not agree to surgery, and to treat hepatocellular carcinoma which is local but inoperable (e.g,, due to poor performance status or presence of comorbidity). NCCN guidelines make no distinction with respect to these different ablative methods.

nccn,org, hepatobiliary, p. 16

Basics of Cryosurgery by Nikolai N. Korpan (Springer; 1 edition (December 18, 2001), Ch.9

Tarceva for biliary cancer – pro

M Levin, MD — Thu, 30 Aug 2012 02:34:52 +0000

Erlotinib has shown activity individually, as single drugs, or in combination with chemotherapy in upper gastro-intestinal cancers, including esophageal and gastro-esophageal adenocarcinomas, gastric cancer and pancreatic cancer. Overexpression of EGFR has been reported to be observed in 10.7%, 5.1%, 12.4% and 0% of cases of intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer and ampulla of Vater cancer, respectively

In a recent study, forty-two patients with biliary cancer were enrolled. Seven of the patients (17%; 95% CI, 7% to 31%) were progression free at 6 months. Three patients had partial response These results suggest a therapeutic benefit for EGFR blockade with erlotinib in patients with biliary cancer. The authors conclude that additional studies with erlotinib as a single agent and in combination with other targeted agents are warranted in this disease. Another phase II study is referenced. There are also studies in combination with bevacizumab or gemcitabine. Lubner et al enrolled fifty-three eligible patients. Of 49 evaluable patients, six (12%; 95% CI, 6% to 27%) had a confirmed partial response. Stable disease was documented in another 25 patients (51%). Median OS was 9.9 months, and TTP was 4.4 months.

SPhilip PA, Mahoney MR, Allmer C, Thomas J, Pitot HC, Kim G, Donehower RC, Fitch T, Picus J, Erlichman Phase II study of erlotinib in patients with advanced biliary cancer.J Clin Oncol. 2006 Jul 1;24(19):3069-74.

Philip, Philip A., Mahoney, Michelle R., Allmer, Cristine, Thomas, James, Pitot, Henry C., Kim, George, Donehower, Ross C., Fitch, Tom, Picus, Joel, Erlichman, Charles
Phase II Study of Erlotinib in Patients With Advanced Biliary Cancer
J Clin Oncol 2006 24: 3069-3074

Dragovich T, Huberman M, Von Hoff DD, Rowinsky EK, Nadler P, Wood D, Hamilton M, Hage G, Wolf J, Patnaik A. Erlotinib plus gemcitabine in patients with unresectable pancreatic cancer and other solid tumors: phase IB trial. Cancer Chemother Pharmacol. 2007 Jul;60(2):295-303. Epub 2006 Dec 6.

S A Khan et al, Guidelines for the diagnosis and treatment of cholangiocarcinoma: consensus document Gut 2002;51:

C. D. Anderson, C. Wright Pinson, J. Berlin, and R. S. Chari
Diagnosis and Treatment of Cholangiocarcinoma
Oncologist, February 1, 2004; 9(1): 43 – 57.

S A Khan, A Miras, M Pelling, and S D Taylor-Robinson
Cholangiocarcinoma and its management
Gut, December 1, 2007; 56(12): 1755 – 1756.

F. Leone, Y. Pignochino, G. Cavalloni, and M. Aglietta
Targeting of Epidermal Growth Factor Receptor in Patients Affected by Biliary Tract Carcinoma
J. Clin. Oncol., March 20, 2007; 25(9): 1145 – 1145.

Sam J. Lubner, Michelle R. Mahoney, Jill L. Kolesar, Noelle K. LoConte, George P. Kim, Henry C. Pitot, Philip A. Philip, Joel Picus, Wei-Peng Yong, Lisa Horvath, Guy Van Hazel, Charles E. Erlichman and Kyle D. Holen

Lubner SJ, Mahoney MR, Kolesar JL, Loconte NK, Kim GP, Pitot HC, Philip PA, Picus J, Yong WP, Horvath L, Van Hazel G, Erlichman CE, Holen KD. Report of a Multicenter Phase II Trial Testing a Combination of Biweekly Bevacizumab and Daily Erlotinib in Patients With Unresectable Biliary Cancer: A Phase II Consortium Study JCO July 20, 2010 vol. 28 no. 21 3491-3497

Dickler MN, Rugo HS, Eberle CA, et al.(2008) A phase II trial of erlotinib in combination with bevacizumab in patients with metastatic breast cancer. Clin Cancer Res 14:7878–7883.

Thomas MB, Morris JS, Chadha R, et al.(2009) Phase II trial of the combination of bevacizumab and erlotinib in patients who have advanced hepatocellular carcinoma. J Clin Oncol 27:843–850.

Adjuvant chemotherapy after Whipple’s for cholangiocarcinoma – pro

M Levin, MD — Thu, 30 Aug 2012 02:32:31 +0000

The role of adjuvant chemothhapy after complete resection of cholangiocarcinoma is changing. The cancer have a high incidence of local failure after surgical resection reaching 52%, a locoregional adjuvant treatment may be considered. Several retrospective reports on adjuvant and recently also on neoadjuvant (chemo)radiotherapy suggest survival benefit in both gallbladder and biliary duct cancer and postoperative chemoirradiation may be considered as an option. Fluorouracil was mostly used for chemoradiotherapy in biliary cancers. Recently concomitant gemcitabine with or without oxaliplatin has shown feasibility with radiotherapy in this disease.” In contrast, a 2008 guideline does not support adjuvant chemo outside of clincal trials.

For extrahepatinc cholangiocarcinoma, NCCN recommend chemoradiation with floropyrimidines and then adjvant chemo with the same or gemcitabine based. It does the same or a clincal trial for clean margins, excluding the chemoradiation. It does not mention oxaliplatin.

F. Eckel, T. Brunner S. Jelicand On behalf of the ESMO Guidelines Working Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up Ann Oncol (2010) 21 (suppl 5): v65-v69.

Junji Furuse, Tadahiro Takada, Masaru Miyazaki, Shuichi Miyakawa, Kazuhiro Tsukada, Masato Nagino, Satoshi Kondo, Hiroya Saito, Toshio Tsuyuguchi and Koichi Hirata, et al.
Guidelines for chemotherapy of biliary tract and ampullary carcinomas,
Jrnal of Hepato-Biliary-Pancreatic Surgery
Volume 15, Number 1, 55-62

nccn.org, chalngiocarcinoma,

Hepatoblastoma – pro

M Levin, MD — Thu, 30 Aug 2012 02:30:11 +0000

Hepatoblastoma is a rare pediatric cancer that can be cured by surgery. Preoperative chemotherapy followed by complete surgical excision according to International Society of Paediatric Oncology guidelines yields excellent results with a current survival rate of 80%.Liver transplantation is a curative option as well.Various chemotherapy regimens have been reported but there are no prospective studies and no studies of second line chemotherapy. Czauderna P, Otte JB, Aronson DC, Gauthier F, Mackinlay G, Roebuck D, Plaschkes J, Perilongo G; Childhood Liver Tumour Strategy Group of the International Society of Paediatric Oncology (SIOPEL).Guidelines for surgical treatment of hepatoblastoma in the modern era–recommendations from the Childhood Liver Tumour Strategy Group of the International Society of Paediatric Oncology (SIOPEL).Eur J Cancer. 2005 May;41(7):1031-6.
Davies JQ, de la Hall PM, Kaschula RO, Sinclair-Smith CC, Hartley P, Rode H, Millar AJ.Hepatoblastoma–evolution of management and outcome and significance of histology of the resected tumor. A 31-year experience with 40 cases.J Pediatr Surg. 2004 Sep;39(9):1321-7.
Pritchard J, Brown J, Shafford E, et al.: Cisplatin, doxorubicin, and delayed surgery for childhood hepatoblastoma: a successful approach–results of the first prospective study of the International Society of Pediatric Oncology. J Clin Oncol 18 (22): 3819-28, 2000. [PUBMED Abstract]
Austin MT, Leys CM, Feurer ID, et al.: Liver transplantation for childhood hepatic malignancy: a review of the United Network for Organ Sharing (UNOS) database. J Pediatr Surg 41 (1): 182-6, 2006. [PUBMED Abstract]

http://www.annalsofhepatology.com/PDF/vol9n1/HP101-13-Hepatoblastoma.pdf

Zsíros J, Maibach R, Shafford E, et al.: Successful treatment of childhood high-risk hepatoblastoma with dose-intensive multiagent chemotherapy and surgery: final results of the SIOPEL-3HR study. J Clin Oncol 28 (15): 2584-90, 2010.

Intrahepatic therapies ablative therapies – pro

M Levin, MD — Mon, 27 Aug 2012 02:32:48 +0000

Percutaneous ablation is a commonly used modality of treatment when resection is not possible for HCC. Other local modalities are radiofrequency ablation or chemo embolization. When direst intratumor injection is used, alcohol is most commonly used and it is FDA approved for this purpose. However, acetic acid is more potent in animal models. Only a few studies tested the various modlaities against one another.

A systematic review of RCTs published from 1978 to 2002 identified seven RCTs including a total of 516 patients comparing embolization vs. conservative management, five of which assessing chemoembolization with doxorubicin or cisplatin. Survival benefits were obtained in two studies, one of which identifies treatment response as an independent predictor of survival. Meta-analysis showed a beneficial survival effect of embolization/chemoembolization in comparison with the control group. Overall, this effect may be considered modest, as is expected to occur in advanced neoplasms. Survival benefits were not identified with embolization alone, but the number of individuals analyzed is still low. There is no good evidence for the best chemotherapeutical agent and the optimal re-treatment strategy.

Three small RCT assessing either chemoembolization in combination with percutaneous ablation or lipiodolization have been published in this period A German study reported no survival differences between a combination of chemoembolization and PEI vs. chemoembolization alone in 58 patients. Therapy using reservoir intra-arterial infusion has been employed in patients with advanced HCC with disappointing results. A low-quality study assessing lipiodolization with carboplatin (150 mg/m2) compared with doxorubicin (20 mg/m2) in 65 Chinese patients, showed significant survival benefits favoring the carboplatin arm (16.9 vs. 12.1 months, P = 0.0257). Further studies are required to confirm these data.

In summary, there is no conclusive evidence to consider intrahepatic injection to be better or even equivalent to emblolization; however, alcohol ablation is widely used in the USA. Acetic acid is less frequently used and there are no comparative studies of it versus alcohol. NCCN speaks of “ablation” and thus avoids the issue of the agent (alcohol versus acetic acid);however, it considers “ablation” standard of care.

Brunken C, Topp S, Tesch C, et.al. System Effects and Side Effects of Interstitial Techniques Used in Liver Tissue. American College of Surgeons 1999; 188, No.6: 636-642.

Usha Dutta (2000) Treatment of hepatocellular carcinoma Journal of Gastroenterology and Hepatology 15 (8), 822–824.

Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 2003; 37: 429–42.

Akamatsu M, Yoshida H, Obi S, et al. Evaluation of transcatheter arterial embolization prior to percutaneous tumor ablation in patients with hepatocellular carcinoma: a randomized controlled trial. Liver Int 2004; 24: 625–9.

Becker G, Soezgen T, Olschewski M, et al. Combined TACE and PEI for palliative treatment of unresectable hepatocellular carcinoma. World J Gastroenterol 2005; 11: 6104–9.

http://nccn.org/professionals/physician_gls/PDF/hepatobiliary.pdf