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Hi, everyone,
something for you if you like to read about CCA.

Overview of Cholangiocarcinoma for ipad users

During liver development, hepatoblasts differentiate into hepatocytes and biliary cells which delineate the bile ducts. More than 90% of the bile duct cancer (cholangiocarcinoma) are well to moderately differentiated adenocarcinomas.
Cholangiocarcinoma (CCA) is an epithelial cancer of the bile duct that can be intrahepatic (20-25%) or extrahepatic such as perihilar tumor(50%) and distal bile duct cancer(20-25%). CCA represented about 13% of primary liver cancers and is the second most common primary liver after hepatocellular carcinoma. The prevalance of liver and intrahepatic CCA (ICCA) shows highest in China for men(95 per 100,000 )and Thailand for women( 35 per 100,000);
In general, CCA are rare in Europe and the USA, accounting for % of all GI tumors. In the United States, the incidence of CCA is approximately 7,000 new cases/year .In UK,it is about 1,500 cases/year ;in Japan, according to the health ministry,there were 13,000 deaths in 2010 alone and in South Korea, it is about 3,500 new cases per year.For unknown reasons the incidence of intrahepatic CCA occurrence has been increasing worldwide from North America, Europe, Asia and Australia; Country like Italy reported a 40-fold increase in intrahepatic CCA mortality from 1980-2003. In contrast, the mortality rate of extrahepatic CCA (ECCA) is declining worldwide.

The most common risk factors for patient in United States and Europe are the inflammatory disease like primary sclerosing cholangitis (25-30%), ulcerative colitis and congenital choledochal cysts. In Asia, and other parts of the world like Middle East, parasitic infections, hepatitis B,C infections, HIV, biliary tract stones diseases ; chemical agents like Thorotrast, dioxin, alcohol, early formulary of oral contraceptive,isoniazid and smoking; age>65(range:20-90’s) ,diabetes and obesity are known risk factors for CCA.
By the time the symptoms of CCA (Jaundice, itching, right upper abdominal pain, weight loss ,light color stools , dark urine) show up, normally it will too late for surgery. Surgery like resection and orthotopic liver transplant provide the only possible cure ; stage III and IV CCA are generally considered unresectable. Clinical staging is fundamental in pre-surgical evaluation using MRCP,ERCP, EUS, Doppler US, CT, MRI and PET. PET scan changes the surgical management in a third (33%) of patients. In a large study, the resectability rates for intrahepatic , perihilar and distal lesions were 60%, 91% and 56%.

For ICCA patients,five-year survival rates after resection is around 22-44% and correlate with R0 margin (clear margin), lymph node involvement and vascular invasion. Recurrence is very common(>75%) after liver resection. Re-resection, TACE, RFA , SBRT, and radioembolization are radiological approach for treatment while chemotherapy with Gemcitabine ,5 FU(including capecitabine,S1), cisplatin,carboplatin,oxaliplatin , irinotecan, paclitaxel ,docetaxel ; molecularly targeted agents like sorafenib erlotinib ,cetuximab and bevacizumab ,and the combination using of them or joining clinical studies are other choices to extend the life of ICCA patients.

For ECCA patients, biliary drainage either by endoscopic or percutaneous stenting will provide relief of the biliary obstruction. Recurrence after resection are common in ECCA patients. Systemic treatment are the same as ICCA above; radiation therapy such as brachytherapy,EBRT, PDT, SBRT, and the more advance tomotherapy IMRT and Robotic Linac IMRT ; orthotopic liver transplant ,and clinical trials are acceptable to prolong life expectancy. Five-year survival rate for ECCA is around 20-50% and for liver transplant patient (68%). If untreated, life expectancy is about 4-12 months.
Among patients who undergo resection for CCA, long term outcomes depending on the histologic margin, lymph node involvement , location ,
number and stage of the lesions, the extent of the surgery, the general health of the patient and treatment-related complications. The benefit of adjuvant chemotherapy and /or radiation therapy is controversial at best.

Quantity vs the quality of life should be always considered for the overall benefit of the patient. Multimodality approaches should be considered to improve the outcome for both the resected patients and unresectable CCA patients.Above all ,since surgery provides the only possible cure . Establishment of effective early detection tests using biomarkers and development of new molecularly targeted agents are urgently needed to provide more effective treatment with less adverse reactions to the CCA patients.

References:
1. Cornelia Braicu et al .Molecular markers in the Pathogenesis of CCA :Potential for Early Detection.
Gastroenterology Res,Vol 2.No. 3,Jun 2009
2. Christopher Anderson,MD et al. Treatment of localized Cholangiocarcinoma: surgical management and adjuvant therapy. Literature review version 19.1: May,2011.
3. Tushar Patel. Cholangiocarcinoma-controversies and challenges: Gastroenterology & Hepatology vol.8,Apr.2011
4. Manuela Gatto, domenico Alvaro.et al> New Insights on cholangiocarcinoma: World J Gastrointest oncol. 2010 March 15 ;2(3): 136-145.
5. Murad Aljiffry,Alhawsawi Abdulelah et al. Evidnece-based approach to Cholangiocarcinoma: a systematic Review of the Current Literature: doi:10.1016/j.jamcollsurg.2008.09.007.
6. National Center Center,Korea,Republic of.
7. Michael Tedesco,Univ.of Rochester medical center web site 3/5/2012
8. http://www.yomiuri.co.jp/dy/national/T120711003755.htm
9. http://www.cholangiocarcinoma.org/punbb/viewtopic.php?id=7730
10. http://www.cholangiocarcinoma.org/punbb/viewtopic.php?id=8542
God bless.

Greetings Foundation Supporters and Affiliates,

I had the unique opportunity to attend the 2012 GI Cancers Symposium: Science and Multidisciplinary Management of GI Malignancies in San Francisco as volunteer support for Marion’s advocacy and outreach. This confernece brings together and international community of researchers, physicians, and partners in addressing gastrointestinal forms of cancer. Having had the loss of my mother, Nancy Galarneau, at the tender age of 52 in a 2 and a half month assault of cholangiocarcinoma in spring-summer 2009 I have grown since then in my awareness and concern at the level of uncertainty of viable treatment and knowledge creation on seeking new methods for intervention. The technical jargon was more accessible then I imagined in reviewing poster abstracts and proceedings once orientated to a few pointers from Marion. There were three days of sessions with the second day featuring more content relative to Cholangiocarcinoma. Below is a synthesis of related poster presentations and abstracts I thought would be useful for those supporting treatments for loved ones dealing with this cancer or for those brave souls serving as advocate and patient themselves. The entire proceedings can be accessed through this link https://docs.google.com/viewer?a=v&pid=explorer&chrome=true&srcid=0B3nbi8Y3dWuXZGY2OTFmYjEtZGZmYi00N2EwLWI0ZDctNDc4Mjg2N2Q0NDdk&hl=en_US so folks can look through the posters and session paper presentations in their entirety for those wanting to dig deeper.

Overall I found the experience to speak to an untapped potential that Marion and her volunteer network is attempting to realize: one in which international and domestic researchers and oncologists can advance treatment and diagnostic tools for addressing this horrid cancer. One of the challenges as with many other cancer treatment processes, is reconciling the private and company driven trial and research with the more open and transparent task forces comprised of the GI field of experts in combating through public and government based funded procedures. Knowing how much $$ it costs to bring a drug to the market tells me we’ll have to somehow reconcile the private and public to work together on this, and more then likely, the findings of related and greater diagnosed cancers will help pave the way for advancing the foundation’s agenda.

Selected Abstract and Poster Recap (more detail in the link to full proceedings)
https://docs.google.com/viewer?a=v&pid=explorer&chrome=true&srcid=0B3nbi8Y3dWuXZGY2OTFmYjEtZGZmYi00N2EwLWI0ZDctNDc4Mjg2N2Q0NDdk&hl=en_US

• (Abstract # 158) SBRT as an alternative to RFA for the treatment of primary and metastatic liver tumors. Presenting Author: Erqi Liu, University of Michigan, Ann Arbor, MI.

Background: Radiofrequency ablation (RFA) is a widely used local therapy for small, unresectable liver tumors (LT). Stereotactic body radiotherapy (SBRT) has been used for similar patients, and has the advantage that it can be used when lesions are adjacent to blood vessels, are difficult to reach and cannot be imaged on ultrasound. Conclusions: SBRT is a safe alternative to RFA, can be used in a wider variety of patients, and may be more effective than percutaneous RFA at locally controlling larger liver tumors.

• (Abstract #176) Value of preoperative biopsy and radiological assessment for the diagnosis of mixed hepatocellular cholangiocarcinoma (HCC-CC). Presenting Author: Mohamed Bouattour, Department of Oncology, Beaujon University Hospital, Clichy, France

Background: Mixed tumors with hepatocellular and cholangiocarcinoma component (HCC-CC) are rare variants of primary liver tumors. In this study, we aimed to describe clinical, radiological and histopathological features of patients with resected HCC-CC. Conclusions: Mixed HCC-CC are not accurately identified by preoperative biopsy using only morphological features and CT scan/MRI assessment. Following resection, mixed HCC-CC behave more like CC than HCC.

• (Abstract #207) This one is funded by the foundation and Marion noted in her announcement on the website. Significance of CEACAM6 expression in biliary tract carcinoma. Presenting Author: Flavio G. Rocha, Virginia Mason Medical Center, Seattle, WA

Background: The entire biliary tree is at risk for malignant change, but little is known about differences in molecular pathogenesis with respect to anatomic site. CEACAM6 is a membrane protein involved in cell adhesion and signaling that is overexpressed in pancreatic adenocarcinoma and associated with poor prognosis. This study examines CEACAM6 expression in the entire spectrum of biliary carcinomas and its relationship to outcome. Methods: Tissue microarrays containing triplicate Conclusions: CEACAM6 may serve as a marker of poor outcome in patients with intrahepatic cholangiocarcinoma and should be further evaluated as a means of selecting patients for adjuvant therapy after resection

•(Abstract #255) Randomized phase II trial of gemcitabine plus S-1 combination therapy versus S-1 in advanced biliary tract cancer: Results of the Japan Clinical Oncology Group study (JCOG0805). Presenting Author: Chigusa Morizane, National Cancer Center Hospital, Tokyo, Japan

Background: Gemcitabine plus cisplatin combination (GC) therapy is the standard therapy for advanced biliary tract cancer (BTC). In previous trials, gemcitabine plus S-1 combination (GS) therapy and S-1 monotherapy had shown considerable efficacy in patients with BTC. The aim of this trial is to evaluate the efficacy and safety of the two regimens and to determine which is more promising as a test arm regimen for a subsequent phase III trial. Conclusions: The GS arm was superior in %1-year survival to S-1. Here we consider GS to be more promising as the test arm for a subsequent phase III trial comparing with GC.

• (Abstract #268) Cholangiocarcinoma: A joint cancer database analysis. Presenting Author: Yehuda Ethan Deutsch, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL

Background: Cholangiocarcinoma is an uncommon malignancy. In addition,only 10-30% of patients are eligible for curative surgical resection due to advanced disease at diagnosis. The role of adjuvant therapy is not yet established. The objective of this analysis is to assess the outcome of patients with cholangiocarcinoma managed with surgery, chemotherapy, radiation, and/or chemo-radiation. A total of 800 patients with the diagnoses of biliary cancer were reviewed. Conclusions: Chemotherapy and chemo-radiation had a positive impact on survival in patients with late stage cholangiocarcinoma. Surgery improved survival in both early and advanced stages.

• (Abstract #328) An interim evaluation of efficacy and safety of the combination of panitumumab, gemcitabine, and irinotecan in patients with advanced or metastatic cholangiocarcinoma: A phase II study. Presenting Author: Weijing Sun, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA

Background: Cholangiocarcinoma is an aggressive neoplasm. Current chemotherapy approaches suggest that combinations may be superior to single agents in this disease. Over-expression of epidermal growth factor receptor (EGFR) is associated with tumor stage and prognosis. This study was designed to evaluate the efficacy and tolerability of the combination of panitumumab, a monoclonal anti-EGFR antibody, with gemcitabine and irinotecan in patients with advanced and metastatic cholangiocarcinoma. Conclusions: The data of this on-going study showed encouraging results of the combination of panitumumab with gemcitabine and irinotecan in both tolerability and efficacy. The pre-specified efficacy criteria to continue enrollment were met. Further analysis by biomarker status (KRAS/BRAF/EGFR) is forthcoming

• (Abstract #377) Evaluation of chemotherapy with cisplatin plus gemcitabine after failure of gemcitabine alone for unresectable or recurrent biliary tract cancer. Presenting Author: Ryo Kameda, Division of Gastroenterology, Kanagawa Cancer Center Hospital, Yokohama, Japan

Background: As there was no standard chemotherapy for advanced biliary tract cancer before ABC-02, we had treated our patients with gemcitabine alone. However, recently cisplatin plus gemcitabine became standard as first line chemotherapy. We assessed the benefits of chemotherapy with cisplatin plus gemcitabine after failure of gemcitabine alone before ABC-02 era. Conclusions: Cisplatin plus gemcitabine can be an optional therapy for unresectable or recurrent biliary tract cancer after failure of gemcitabine alone.

Additional Abstract titles to look at in the proceedings:
https://docs.google.com/viewer?a=v&pid=explorer&chrome=true&srcid=0B3nbi8Y3dWuXZGY2OTFmYjEtZGZmYi00N2EwLWI0ZDctNDc4Mjg2N2Q0NDdk&hl=en_US
• (Abstract #161) Endoscopic ultrasound-guided fine needle core biopsy versus aspiration for gastrointestinal mass lesions: A randomized trial. Presenting Author: Nam Q. Nguyen, Royal Adelaide Hospital, Adelaide, Australia
• (Abstract #267) Patterns of recurrence after resection of intrahepatic cholangiocarcinoma: Results from a multi-institutional cohort of 449 patients. Presenting Author: Ioannis Hatzaras, Johns Hopkins University, Baltimore, MD
• (Abstract #288) Biliary tract cancer: A large institutional experience. Presenting Author: Mairead McNamara, Princess Margaret Hospital, Toronto, ON, Canada
• (Abstract #343) 90Y radioembolization for neuroendocrine cancers liver metastases provides sustained therapeutic effect with minimal toxicity. Presenting Author: Andrew S. Kennedy, Cancer Centers of North Carolina, Cary, NC
• (Abstract #346) Developments of treatment of advanced intrahepatic cholangiocarcinoma: An analysis of systemic and local therapy modes in 57 patients. Presenting Author: Patrick Stuebs, Otto-von-Guericke-University, Magdeburg, Germany

Good luck to all those out there in the midst of facing this cancer and keep up the good fight!

Tim

so i got my results from my cat scan my tumors in my lungs decreased by less than a mm but 3 or the tumors in my liver have increased by under a cm so now they want to either switch my chemo or do another biopsy of my liver and check to see which clinical trial can be used once they target the blood of the abnomal cell. has anyone ever done this? I was so sure the chemo was working but i guess not i was supposed to have 3 more months of gemcitabine/cisplatin but now i have to switch and start all over again. Was looking forward to the break after the 3 more months i had. The one in my bile duct is still the same and the other tumors and lymphnodes are the same no changes. i guess thats okay news.

My dad has been getting treatments of cisplatin and gemcitabine since last March.He had really positive response to it and the tumors were shrinking.He started to get some side effects and the oncologist had him take a break over the holidays (since october).Over that break his cancer increased in size again,but only slightly.Dad is so discouraged. He has always been so positive.He will be starting on oxaliplatin and capecitabine for his next treatment.Anyone have any experience with these and what were the results in terms of success? Just reaching for anything right now and trying to keep him positive and informed.He feels great other than when he is on chemo.Thank you.Kathy

Well, I have an appointment with my oncologist today at 1pm. We are discussing final decisions on my adjuvant therapy that starts on Friday the 13th. As of now, I believe they are only putting me on Gemzar but from what I can gather, the combination of Gemzar/Cisplatin is the ‘standard of care’ for CC.

My situation is a bit different in that there is no remaining tumor and the chemo is preventative to hope for a better chance of non-recurrence.

I actually sent an email to Dr. Javle at MD Anderson, gave him my history, and he also suggested a combination Gemcitabine/Cisplatin for 3-4 months with 5.5 weeks of Radiation and oral Xeloda. I am going to bring this up to my oncologist today but really have no clue as to what I should be doing.

Suggestions/comments?? Thanks in advance!

It’s hard to believe that it’s taken me nearly 6 months to find this site. Given my background in online discussion boards and mailing lists, I somehow didn’t think to look and see if there was anything like this for my cancer until within the last couple of weeks.

My name is Eriq Neale, I live in Texas, and I was diagnosed with CC back in March. I started having unusual abdominal pains in mid-January and finally went to see my doctor towards the end of February, because I was schedule to go on a week-long trip and wanted to see if he could do something about the pain while I was on the road so I wouldn’t be uncomfortable while traveling. He did some blood work and found some liver enzymes that he thought were a little suspicious (on the high side of normal). He scheduled me in for a CT, which I had done on a Thursday (I was scheduled to leave town on Sunday). He called me Thursday afternoon to tell me that the CT showed something in my liver and he wanted me to have an MRI to get a better idea what was growing in my liver. He says that he arranged to have the MRI done the next day because he didn’t want this to be “hanging over me” while I was traveling, but I think he saw something in the CT scan that scared him enough that he wanted the diagnosis ASAP. I had the MRI done the following morning. I got a call that Friday afternoon that they were concerned the growth might be cancer and that he wanted to schedule me for a biopsy ASAP. I cancelled my trip and scheduled the biopsy for the following week. The next night, Saturday, the abdominal pain got really intense and I started getting really nauseous, so we ended up going to the ER late that night. I got checked in for observation, and the hospitalist assigned to my case arranged for all kinds of tests to be performed. I’m probably fortunate that I did get checked into the hospital, as all those tests happened within the next two days, instead of having to schedule them as outpatient procedures. My EGD came back clean, as did the colonoscopy. Two days later, the day I was originally scheduled to have the biopsy, I had a PET scan done, and that’s when the hospitalist confirmed that the tumors were likely cancer, as the PET scan showed several areas of likely cancerous growth, including a spot on the outside of the colon. I had the biopsy done the following day, and the pathology showed the tumor was likely from an upper-GI tumor, though none had been found.

We scheduled a procedure with a surgical oncologist at Methodist in Dallas to do a liver resection to remove the tumor from my liver as well as to clean out the other obvious cancerous growths in my abdomen. I had the surgery at the end of March. When he cut me open, he removed several cancerous growths that had shown up on the scans, but also saw small tumors on the underside of my diaphragm. Without major reconstructive surgery, he couldn’t do anything about those tumors, so after completing the rest of the procedure successfully, he recommended that we follow up with chemotherapy. “Aggressive chemotherapy” in his words, because I was “young and in good physical health.”

We started chemo at the first of May and started on Cisplatin and Gemcitabine. That next six weeks was probably the worst of my life. I lost 35 pounds because I couldn’t eat thanks to the nearly-constant nausea. I couldn’t move, I had to sleep in a trundle bed simply because we could lay it close to the floor so I could roll out of it and crawl into the bathroom to throw up. I tolderated the chemo so poorly that after two complete cycles, I was switched over to oxaliplatin, which did little to improve the symptoms. At the end of July, I stopped those chemo treatments and had another CT scan. Unfortunately, it showed continued growth of tumors in my abdomen, though the growth was very small. I started taking Xeloda in August, and my quality of life came back almost immediately. it wasn’t a walk in the park on the Xeloda, but I never had any nausea, and I was able to start eating regularly and start regaining my strength. I also finally fully recovered from the liver surgery during that time, so I was definitely feeling better.

Unfortunately, the scan we did in November still showed continued growth of the cancer, so we’re taking a two-week break and will be starting on Taxol next week. I’m told that it’s well tolerated by chemo patients, but I’m not looking forward to it based on the reading I’ve done on Taxol, some of which ultimately led me to this site. Also, I broke a rib about 3 weeks ago, so I’m dealing with lots of additional pain meds, and i’ve basically spent the last two weeks flat on my back in bed. I’m hoping that I’ll get some sense of “normalcy” back when the rib heals and I can cut back on the pain meds.

I’m trying to get in to MD Anderson and see if they have any other thoughts about my prognosis or additional treatments they might be able to offer. Unfortunately, I decided to wait until nearly Christmas to contact them, and they’ve been really, really slow about responding.

I have been keeping a journal over at Caring Bridge: http://caringbridge.org/visit/eriqneale
That has helped me cope with a lot of what I’ve been going through, as well as keeping our friends and family up to date with the latest information.

I’m looking forward to learning my way around here and finding out more about how people are living with this kind of cancer, what works and what doesn’t as far as treatment, and anything else that might help me better deal with this strange (to me) disease.

Thanks for having this area for us to come to. I’m anxious to see what I can find here, as well as how I can contribute…

-Eriq

My wife had her first session of Gemcitabine/Cisplatin today.

She is complaining about abnormal heartbeat. She says that her heart is “doing something unusual” and is “working extra hard”. She feels that the problem got a bit worse as the day went by.

We just got off the phone with our home care nurse. The guy asked us to check her pulse. The pulse was normal (72). The guy said that normal pulse is a good sign. He said there is no reason to panic. He asked my wife to spend the rest of the day in bed. At the same time, he told us to watch this carefully. He told us to go to ER if the problem gets worse.

Here’s the medication she took today:

Before chemo: IV of Zofran and Dexamethasone at the hospital

After chemo: Advil and Tylenol for a bad headache. We checked with our oncology nurse before taking it. She said fine. The home care nurse also said it’s not a problem.

I’m curious if anyone else experienced abnormal heartbeat after chemo? The feeling that heart is doing something unusual but the pulse stays normal?

I am on my 3rd week of this combo i have the two weeks then one week rest cycle so so far i have only taken it twice. It seems to be okay so far i get upset stomach sometimes and headaches/tiredness a little hair sheding but not much it does get really itchy though i am just wondering if it gets worse as it goes along i have never taken chemo before so im not sure what to expect i heard this is a milder chemo and im not supposed to lose my hair or anything. I also have cealic disease so im allergic to wheat and i cant tell sometimes if my stomach problems are from that or the drugs. Im pretty sure its the drugs because i am very carefull to not eat wheat.
Also is it safe to take peptol bismol if i get diharea i know they give me pills for when im feeling sick but i think that is more for if i have to throw up. I am okay with not taking anything and drinking water and letting it run its course just sometimes if i want to leave the house or if people come over and im feeling sick its not comfortable. i have cancer cells in my liver so i know drugs are hard on it wanted to ask before i do anything to make matters worse than they already are!
One more thing i was wondering is how much hair do people normaly lose on this combo i was told by the oncologist i would lose my hair but the nurses one said no one said i might. its been really itchy and if i run my hands through it a little sheds and when iwash it but not alot so i dont know if it gets worse the more i take the chemo or if now that i have done it twice this is how it is and it will just be like this for the next 6 months. not sure what to expect.