Cancer Treatment Today » Gastrointestinal Diseases

Xifaxin

M Levin, MD — Fri, 27 Dec 2013 17:53:24 +0000

Xifaxin ( rifaximin) is approved by the U.S. Food and Drug Administration to treat traveler’s diarrhea caused by E. coli. It is especially effective for prophylaxis. It is not effective against Campylobacter jejuni, and there is no evidence of efficacy against Shigella or Salmonella species. It is, therefore, narrower in scope than other drugs used for these conditions.

There is evidence that it may be efficacious in relieving chronic functional symptoms of bloating and flatulence that are common in irritable bowel syndrome (IBS). Rifaximin is licensed by the U.S. Food and Drug Administration to treat traveler’s diarrhea caused by E. coli. Clinical trials have shown that rifaximin is highly effective at preventing and treating traveler’s diarrhea among travelers to Mexico, with few side effects and low risk of developing antibiotic resistance. It is not effective against Campylobacter jejuni, and there is no evidence of efficacy against Shigella or Salmonella species.

It may be efficacious in relieving chronic functional symptoms of bloating and flatulence that are common in irritable bowel syndrome (IBS). There was recently a pilot-study done on the efficacy of rifaximin as a means of treatment for rosacea, according to the study, induced by the co-presence of small intestinal bacterial overgrowth.

In the United States, rifaximin has orphan drug status for the treatment of hepatic encephalopathy.

There was recently a pilot-study done on the efficacy of rifaximin as a means of treatment for rosacea, according to the study, induced by the co-presence of small intestinal bacterial overgrowth.

For Professional version see here

Prophylaxis for stress ulcers – pro

M Levin, MD — Wed, 13 Feb 2013 21:21:43 +0000

A variety of medical factors can create stress and place a patient at at risk of gastroduodenal ulcerations and bleeding. Among teh most common are prolonged mechanical ventilation, coagulopathy, multiple injuries, spinal cord injury, injury, acute renal failure, and administration of high-dose steroids. The latter usually ocurrs in the setting of chemotherapy.

A variety of interventions have been studied, including: Histamine-2 receptor antagonists, Proton pump inhibitors , Cytoprotective agents. All of these options are supported by published clinical studies. Several have been found to be ineffective or harmful: Use of antacids has been associated with a potential increase in the risk of hemorrhage. Enteral feeding also has failed to show significant increases in gastric PH but some proponents remain.

Guillamondegui OD, Gunter OL Jr, Bonadies JA, Coates JE, Kurek SJ, De Moya MA, Sing RF, Sori AJ. Practice management guidelines for stress ulcer prophylaxis. Chicago (IL): Eastern Association for the Surgery of Trauma (EAST); 2008. 24 p. [58 references]
http://www.east.org/resources/treatment-guidelines/stress-ulcer-prophylaxis

ASHP therapeutic guidelines on stress ulcer prophylaxis. ASHP Commission on Therapeutics and approved by the ASHP Board of Directors on November 14, 1998. Am J Health Syst Pharm. 1999;56:347-379.(note will be updated in 2012)

For Lay version see here

Octreotide in gastrointentinal angiodysplasia – pro

M Levin, MD — Tue, 18 Dec 2012 22:40:34 +0000

Angiodysplasias are usually asymptomatic but they can cause of GI bleeding in 3–6% of all patients and are a more common cause of beeeding in the elderly. It is notoriously difficult to treat. A number of reports suggest that it is a valuable adjunct in the treatment of gastro-inestinal dysplasia and can decrease bleeding. There are no supportive guidelines to my knowledge but the role of somatostatin analogues for refractory bleeding GI angiodysplasias has been systematically reviewed by Brown et al.
He concluded: “A significant number of patients with bleeding gastrointestinal angiodysplasia respond to treatment with octreotide by reducing the need for blood products. As all the included studies had small sample sizes, multicenter randomized trials are needed to confirm these findings. However, it seems reasonable to administer octreotide especially in patients with refractory bleeding, inaccessible lesions and in patients at high risk for other interventions.”.

Rivera M, Lucero J, Guerrero A, Márquez JL, Montes R, Suñer M, Ruiz A, Valdivia MA, Mateos J. Octreotide in the treatment of angiodysplasia in patients with advanced chronic renal failure.Nefrologia. 2005;25(3):332-5.

Junquera F, Saperas E, Videla S, et al. Long-term efficacy of octreotide in the prevention of recurrent bleeding from gastrointestinal angiodysplasia. Am J Gastroenterol 2007; 102:254.

Brown C, Subramanian V, Wilcox CM, Peter S. Somatostatin analogues in the treatment of recurrent bleeding from gastrointestinal vascular malformations: an overview and systematic review of prospective observational studies. Dig Dis Sci 2010; 55:2129.

Scaglione G, Pietrini L, Russo F, et al. Long-acting octreotide as rescue therapy in chronic bleeding from gastrointestinal angiodysplasia. Aliment Pharmacol Ther 2007; 26:935.

Molina-Infante J, Perez-Gallardo B. Somatostatin analogues for bleeding gastrointestinal angiodysplasias: when should thalidomide be prescribed?. Dig Dis Sci. Jan 2011;56(1):266-7.

Bon C, Aparicio T, Vincent M, et al. Long-acting somatostatin analogues decrease blood transfusion requirements in patients with refractory gastrointestinal bleeding associated with angiodysplasia. Aliment Pharmacol Ther 2012; 36:587.

For Lay version see here

For a discussion of thalidomide see here

Stem and mesenchymal cell transplantation for Crohn’s disease and Ulcerative colitis – pro

M Levin, MD — Sun, 02 Sep 2012 13:01:04 +0000

The incidence and prevalence of Crohn’s disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel diseases (IBD), are rising in western countries. At the same time, stem cell therapies are gaining a prominent place of interest among clincal investigator. at this time, only phase I studies have been performed and are ongoing in patients with Crohn’s disease. Clinical improvements in some IBD patients have been reported after allogeneic and autologous transplantation of stem cells. In addition, various paremeters of immune functions have improved or normalized in several reported patients.

Experimental and clinical data indicate that both hematopoietic and mesenchymal stem cells(MSC, which are present in the marrow or are marrow derived, have great potential for those clinical applications that require tissue regeneration or repair promotion, owing to their plasticity and their immunomodulatory properties. Bone marrow transplantation from an unaffected donor is able to ameliorate pathology in a mouse model of chronic genetic-based colitis. Moreover, CD34- bone marrow- and peripheral blood-derived stem cells contributed to mucosal repair via neoangiogenesis in moderate-severe murine colitis and were effective in reducing the pathologic features associated with IBD. Both HSC and MSC transplantation in IBD are currently being evaluated in Phase III clinical trials.

Giacomo Lanzoni, Giulia Roda, Andrea Belluzzi, Enrico Roda, and Gian Paolo Bagnara Inflammatory bowel disease: Moving toward a stem cell-based therapy World J Gastroenterol. 2008 August 7; 14(29): 4616–4626.

Julián Panés et al, Mesenchymal stem cell therapy of Crohn’s disease: are the far-away hills getting closer?
Gut 2011;60:742-744

CA-19-9 for gastric cancer – pro

M Levin, MD — Tue, 28 Aug 2012 01:11:41 +0000

CA 19-9 is elevated in some cases of gastric cancer and in those cases it is often used to monitor response to chemotherapy. Approximately one third of patients with gastric cancer will have elevated levels of CEA and one third will have elevated levels of CA 19-9; Ca 19-9 is more commonly elevated in pancreatic and biliary cancer. It can be used for detecting early relapse or to monitor therapy. Unfortinately, there is not much credible medical literature defining these used for specifically gastric cancer and many plans, including Anthem do not consider 19-9 to be a medically necessary marker to follow gastric cancer. This approach is defensible based on the literature. Although there is set of Japanese guidelines that recommends Ca 19-9, gastric cancer in Japan is a differently behaving disease than in the West, as is widely recognized, and Japanese practice in gastric cancer is not followed in the USA.

M.J. Gaspara, I. Arribasa, M.C. Cocaa, M. Díez-AlonsobPrognostic Value of Carcinoembryonic Antigen, CA 19-9 and CA 72-4 in Gastric Carcinoma Tumor Biology Vol. 22, No. 5, 2001

V Heinemann, J Stemmler, M Schermuly, P Stieber, K Niebler, R Wilkowski, T Helmberger, M Garbrecht, A Schalhorn CA 19-9: An Early Indicator of Response to Chemotherapy in Advanced Pancreatic Cancer. Proc Am Soc Clin Oncol 19: 2000 (abstr 1076)

PET for pancreatic cancer – pro

M Levin, MD — Tue, 28 Aug 2012 01:10:31 +0000

Pancreatic carcinoma is common in the United States, with approximately 30,000 patients each year diagnosed with pancreatic adenocarcinomas. Patients with inflammatory processes in the pancreas (pancreatitis) but no cancer can sometimes have high FDG uptake that is indistinguishable from cancers and, thus, must be differentiated from patients with cancer. FDG PET is being applied increasingly in pancreatic cancer diagnosis.
A recent literature review of all available studies found this:
For diagnosis: An estimated 50% change was noted in management effect, based on 26 patient studies. For diagnosis/staging: An estimated 43% change was noted in management effect, based on 65 patient studies. For staging: An estimated 36% change was noted in management effect, based on 33 patient studies. For recurrence: An estimated 53% change was noted in management effect, based on 19 patient studies. For monitoring response: An estimated 16% change was noted in management effect, based on 19 patient studies.

Considering the very poor prognosis of pancreatic carcinomas, PET´s greatest role may prove to be in helping to characterize masses appearing in the pancreas, as opposed to more general tumor staging. This is an active area of current investigation.

In terms of distinguishing between benign and malignant disease, the gold standard is percutaneous or open biopsy. If PET were to be used to allow patients with scans suggesting benign masses to avoid biopsy, a very high negative predictive value would be required. The key statistic underlying the negative predictive value is the false negative rate. Patients with false negative results are incorrectly assumed to have benign disease, and are thus not promptly treated for pancreatic cancer. Based on the literature review, the negative predictive value ranged between 75% and 92%, depending on an underlying prevalence of disease ranging from 50%-75%. This level of diagnostic performance may not be adequate to recommend against biopsy. The gold standard is endoscopic ultrasound.NCCN does not recommend PET in the initial workup. On p. PANC-A(2011) it says: “The role of PET/CT remains unclear. PET/CT may be considered after formal pancreatic protocol in high risk patients to detect extra-pancreatic massess. It is not a substitute for high quality contrast enchanced CT”.
The use to diagnose should be considered investigational. Special care is needed to avoid false positives that are common from infection and inflammatioin in this area.

A 2009 guideline says: ” At this time, there are insufficient treatment options that improve the outlook in patients who recur after surgical resection that would allow PET to contribute to management. PET imaging in recurrent disease should be restricted to clinical trials.”

NCCN PANC-2020 says: ” PET/CTcan be considered after formal pancreatic CT protocol in high-risk patient. It isn’t a substitute for high-quality, contrast-ecnchanced CT”.

Recurrence/Restaging

PET is not recommended for clinical management of suspected recurrence, nor for restaging at the time of recurrence, due to insufficient evidence and lack of effective therapeutic options.

Surveillance

NCCN advises suveillance 3-6 months for 2 years, then annually, but with CT and not PET.

http://www.petscaninfo.com/zportal/portals/phys/clinical/jnmpetlit/index_html/JNM_OncoApps

Matchar DB, Kulasingam SL, Havrilesky L, et al. and the Duke Center for Clinical Health Policy Research and Evidence Practice Center. Positron emission testing for six cancers (brain, cervical, small cell lung, ovarian, pancreatic and testicular). Technology Assessment. Prepared for the Agency for Healthcare Research and Quality (AHRQ). Rockville, MD: AHRQ; February 12, 2004.

Kanjeekal S, Biagi J, Walker-Dilks C. PET imaging in pancreatic cancer: recommendations. Toronto (ON): Cancer Care Ontario (CCO); 2009 Jan 19. 20 p. (Recommendation report – PET; no. 5). [34 references]

Ana Beatriz Kinupe Abrahao, Yee Ung, Yoo-Joung Ko, Scott R. Berry; FDG PET/CT in pancreatic cancer staging and management: A retrospective study. Journal of Clinical Oncology 35, no. 4_suppl (February 2017) 464-464.

M. Ducreux et al, Cancer of the pancreas: ESMO Clinical Practice, Guidelines for diagnosis, treatment and follow-up. Annals of Oncology
26 (Supplement 5): v56

Gemcitabine and irinotecan for pancreatic cancer – pro

M Levin, MD — Tue, 28 Aug 2012 01:08:45 +0000

Lay Summary: Gemcitabine and irinotecan appears to be no better than gemcitabine alone

The combination of irinotecan and gemcitabine has been studied in pancreatic cancer. Rocha Lima and colleagues randomized 360 patients to either gemcitabine 1000 mg/m2 and irinotecan 100 mg/m2 on days 1 and 8 every 21 days (gem/irino) or the standard gemcitabine regimen (gem). The arms were well balanced as to age, performance status, metastatic disease, and prior radiotherapy. Diarrhea and nausea/vomiting were worse for patients on the gem/irino arm. While the gem/irino combination was associated with a higher response rate, overall survival and time to tumor progression were similar in both groups. The overall survival for the gem/irino and gem arms was 6.3 months and 6.6 months, respectively. Except for diarrhea, toxicity was very similar between both groups.

The combination of gemcitabine and irinotecan was clearly no better than single-agent gemcitabine. The study that compared the regimens should serve as a cautionary note to investigators regarding phase 2 results. While promising results from the phase 2 study of gemcitabine and irinotecan prompted the launch into this phase 3 trial, it is becoming increasingly clear that response rates in phase 2 trials for pancreatic cancer are often unreliable surrogates for overall survival. For example, in the phase 2 study, the median survival was 5.7 months, which is very similar to the 6.3-month median survival seen in the phase 3 study.

Rocha Lima CM, Sherman CA, Brescia FJ, Brunson CY, Green MR.Irinotecan/gemcitabine combination chemotherapy in pancreatic cancer.Oncology (Williston Park). 2001 Mar;15(3 Suppl 5):46-51.

PET for GIST – pro

M Levin, MD — Tue, 28 Aug 2012 01:06:19 +0000

Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal tract (GIT). About 5000 to 6000 new cases of GISTs are diagnosed in the United States annually. Response to conventional chemotherapeutic agents and radiation therapy is disappointing. Early experience with the tyrosine kinase inhibitor, STI-571 (Gleevec, imatinib mesylate), has been extremely encouraging and it is now an FDA approved treatment.

The role pf PET is udner investigation. Positron emission tomographic scanning with the radiotracer 18F-FDG can reveal early functional changes in tumor glucose metabolism that appear to correlate closely with metabolic response to imatinib mesylate. When compared with CT alone, PET with FDG and PET/CT provided valuable additional information about the extent and metabolic activity of the disease process. The response to drug therapy could be shown as early as 24 hours after completion of a therapeutic regimen.Though very promising, the number of reporteds and the number of published papers is too small to definitely assess sensitivity of PET and PET/CT in evaluating GIST response, as this malignancy is rare. A larger, multicenter study is required.

Antoch G, Kanja J, Bauer S, et al. Comparison of PET, CT, and dual-modality PET/CT imaging for monitoring of imatinib (STI571) therapy in patients with gastrointestinal stromal tumors. J Nucl Med.2004;45:357-365.

Van den Abbeele AD, for the GIST Collaborative PET Study Group. F18-FDG-PET provides early evidence of biological response to STI571 in patients with malignant gastrointestinal stromal tumors [abstract]. Proc Am Soc Clin Oncol. 2001;20:362a; Abstract 1444.

Pancreatic cancer treatment based on BRCA mutations status – pro

M Levin, MD — Tue, 28 Aug 2012 01:03:52 +0000

The concept of individualized therapy is being tested ina clinical trial. One such trial in patients with pancreatic cancer is being run by researchers at Johns Hopkins University:

Olaparib in gBRCA Mutated Pancreatic Cancer Whose Disease Has Not Progressed on First Line Platinum-Based Chemotherapy (POLO)

NCT02184195.

There are other clinical trials of the strategy to target BRCA in pancreatic cancer.

A recent report showed that Olaparib produced a tumour response rate of 26.2% in several advanced cancer types associated with BRCA1 and BRCA2 mutations. The response rate provides new hope for patients with ovarian, breast, pancreatic and prostate cancers whose disease has not responded to standard therapies. The trial enrolls patients with previously untreated, advanced or recurrent pancreatic cancer and a mutation in the BRCA2 gene. The BRCA2 gene confers greatly increased risk of breast and ovarian cancer in addition to a substantial increase in pancreatic cancer risk. At this time,pending more published date, the strategy of diagnosing BRCA in order to provide individualized therapy remains investigational.

NCCN.ORG. Pancreatic Cancer 2017

Kaufman B, Shapira-Frommer R, Schmutzler RK, et al. Olaparib Monotherapy in Patients With Advanced Cancer and a Germline BRCA1/2 Mutation. JCO 2014; Published online before print November 3. doi: 10.1200/JCO.2014.56.2728

Julia B Greer, David C Whitcomb et al, Role of BRCA1 and BRCA2 mutations in pancreatic cancer Gut 2007;56:601-605

Intrahepatic chemotherapy for colon cancer metastases – pro

M Levin, MD — Tue, 28 Aug 2012 01:01:19 +0000

The potential value of hepatic intra-arterial chemotherapy (HIAC) can be considered from several different perspectives. A fundamental assumption for this discourse requires that, in this evaluation, HIAC is being provided with the intent of providing regional hepatic therapy for metastatic hepatic disease. Despite advances in colon cancer (CRC) screening, surgical techniques, and several novel adjuvant agents, CRC continues to be a significant medical challenge. In the United States, approximately 130,000 cases of colon cancer are diagnosed annually. Of these patients, approximately 60% will ultimately develop metastatic disease, and <30% of the initial patient population will have disease confined to the liver.

Ample evidence exists in support of HIAC as the preferred route of administration of regional hepatic chemotherapy: it achieves higher intrahepatic drug concentrations and excellent tumor response rates when compared with other routes of administration. HIAC is an effective form of regional chemotherapy for hepatic metastases. Nearly all studies demonstrate a tendency toward or a significant decrease in hepatic tumor progression when HIAC is used. It is also clear from the data reviewed that regional control of hepatic disease without or independent of systemic disease control does not confer a survival advantage.

To date, the QOL of patients undergoing HIAC has not been adequately evaluated or compared with other treatment modalities. The studies available do not permit any conclusions about the QOL of patients receiving HIAC. Future studies should include QOL among the secondary outcomes in evaluating HIAC.

To date, 10 RCTs have been published, for a total of 1,277 patients enrolled. For tumor response rates, relative risks (RR) and their 95% CIs were obtained from raw data; for OS, hazard ratios (HRs) and their 95% CIs were extrapolated from the Kaplan-Meier survival curves.

Currently available evidence does not support the clinical or investigational use of fluoropyrimidine-based HAI alone for the treatment of patients with unresectable CRC liver metastases, at least as a first-line therapy.

Going to a different setting, the use of HAI of FUDR and systemic 5-FU/LV following resection of hepatic metastases clearly decreases local recurrence and can improve 2-year survival, and further study of HAI in this setting is warranted. Both hepatic and extrahepatic relapses remain a problem and, therefore, initial studies combining HAI with newer systemic agents, such as irinotecan and oxaliplatin, are under way. These should provide a framework to guide us as to which combination regimens are the most effective and well-tolerated. Ultimately, this should lead to randomized trials of HAI therapy plus systemic chemotherapy versus our most active systemic chemotherapy alone in order to determine the best approach to treating hepatic CRC metastases.

http://www.annalssurgicaloncology.org/cgi/reprint/13/2/142.pdf

Evan S. Ong, MD, Madeleine Poirier, MDCM, MSc, FRCS(C) and N. Joseph Espat, MD, MS, FACS
Hepatic Intra-Arterial Chemotherapy Annals of Surgical Oncology 13:142-149 (2006)

S. Mocellin, P. Pilati, M. Lise, and D. Nitti
Meta-Analysis of Hepatic Arterial Infusion for Unresectable Liver Metastases From Colorectal Cancer: The End of an Era?
J. Clin. Oncol., December 10, 2007; 25(35): 5649 – 5654.