Cancer Treatment Today » Colon Cancer

Capsule Endoscopy

M Levin, MD — Thu, 26 Dec 2013 16:28:20 +0000

Capsule Endoscopy(CE) is a procedure in which a capsule with a miniature camera is swallowed and it transmits images as it goes through the gastrointestinal tract. It has advantages and disadvantages. While easier on the patient, it does not allow for a biopsy, and if it shows a suspicious findings, full endoscopyto perform a biopsy will still be required. A recent European guideline says that patients at high risk for CRC, because of symptoms or signs consistent with cancer, or a family or personal history of CRC, are at increased risk of advanced colorectal neoplasia and cancer. These patients should be referred to colonoscop, so a biopsy can be immediately performed. However, in patients for whom colonoscopy is inappropriate or not possible, the use of CE could be discussed with the patient (Evidence level 4, Recommendation grade D). A recent review of various guidelines by Shim et al, confirms this recommendation.

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Weekly 5 FU

M Levin, MD — Thu, 21 Feb 2013 03:19:15 +0000

Fluoropyrimidine (5-fluorouracil [5-FU] is the oldest chemotherapy drug for colon cancer and it is usually given with leucovorin [LV]. , It has a long history of its use for colorectal metastatic cancer and support from many older papers.

Unfortunately, the issue ofweekly versus every three weeks schedule for 5FU.leukovorin has not been resolved, and with the appearance of many new drugs, has receded into the past and is no longer of actual importance to a significant number of patients. Older evidence from phase II trials suggests that weekly 5-fluorouracil and leucovorin have lower toxicity.

The FDA has not weigned in on the schedule. The indication states that Fluorouracil is effective in the palliative management of carcinoma of the colon, rectum, breast, stomach and pancreas.

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Gemzar for colon and rectal cancer

M Levin, MD — Fri, 09 Nov 2012 19:17:56 +0000

Gemzar( gemcitabine) has been tested for colon and recatl cancer. A 1992 study found that Gemcitabine did not demonstrate activity against advanced colorectal adenocarcinoma. ON teh other hand,a much later study found that Gemcitabine has a modest activity in heavily pre-treated colorectal cancer patients and may be an option in good performance status patients. There are a number of reports and ongoing studies of gemcitabine in combination for colorectal cancer. A recent study, Gemcitabine in Treating Patients With Advanced Colorectal Cancer, NCT00007943, was completed in 2009 but not published as of 2012.

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Colovantage test

M Levin, MD — Sun, 28 Oct 2012 16:12:23 +0000

ColoVantage is a new test available from Quest. Although it is a screening test, Quest says that it is not meant to be a substitute for colonoscopy. It was approved by NY State in March of 2011. It detects circulating methylated DNA from the SEPT9 gene, which is involved in cell frowth and cell cycle control. A case-control study performed at Quest Diagnostics showed that the ColoVantage test is 70% sensitive for colorectal cacner detection at a specificity of 89%. ColoVantage has successfully detected cancer at all stages; however, the number of patients at each stage of cancer was too small to derive stage-specific sensitivity data. A similar test demonstrated a sensitivity of 67% and a specificity of 88% in a prospective study of almost 8000 people. Unfortinately, at this time, it remains a proprietary test that has not been sufficiently studied. These findings need to be confirmed in larger studies that evaluate the clinical utility of this test. Support for this test in guidelines from professional organizations is lacking.

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PET for possibly recurring colon cancer

M Levin, MD — Sun, 23 Sep 2012 18:38:25 +0000

After definitive treatmetn of colon cancer, patients are followed with CEA levels. When they begin to rise, a recurrence is suspected. PET is being more frequenlty used to detect and identify recurrence in this situation. More recently NCCN has been more supportive of PET in this setting. It used to support PET only in the situation of rising CEA and no identified recurrence for localization of disease recurrence in patients with rising CEA level and non-diagnostic CT scans. However, PET scan can potentially identify occult disease in this setting that CT may miss. Therefore, PET scans can led to more potentially curative resection in patients with elevated CEA and patients who are candidates for resection of isolated colorectal cancer liver metastases. PET scan prior to attempted resection also reduces the number of unnecessary surgeries.

On p. Col-9, 2012 NCCN recommends the use of CT scans of chest and abdomen in the situation of serial CEA elevations but also says “Consider PET/CT scan”.

CMS guidelines state that PET would rarely be used in the diagnosis of colorectal cancer. However, starting July 1, 2001, HCFA, now called the Centers for Medicare and Medicaid Services (CMS), is covering FDG-PET imaging for diagnosis, staging, and restaging of colorectal cancer.

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Xeloda and irinotecan for second or later lines in colorectal cancer

M Levin, MD — Sun, 23 Sep 2012 17:53:29 +0000

The issue that we will discuss is Xeliri (Xeloda and irinotecan) in second or later line of therapy. It is a tempting regimen because Xeldoa is an generally effective drug for colorectal cancer and it is oral. We start by pointing out that there are now six different classes of drugs with significant antitumor activity in colon cancer:

Fluoropyrimidine (5-fluorouracil [5-FU] which is usually given with leucovorin [LV], capecitabine, tegafur plus uracil [UFT]). Irinotecan, Oxaliplatin, Cetuximab and panitumumab. The latter two are monoclonal antibodies (MoAbs) directed against the epidermal growth factor receptor (EGFR), and bevacizumab, is a monoclonal antibody targeting vascular endothelial growth factor (VEGF). Zaltrap was recenlty(2012) also approved.

The best way to combine and sequence all of these drugs to optimize treatment is not yet established, although for intial treatment of metasatic colorectal cancer NCCN recommends combinations of 5FU and Lekovorin with oxaliplatin or irinotecan with or without Avastin, CAPEOX, 5FU/Leukovorin, Xeloda and Avastin or Folfoxiri.

For second or third line therapy, single agents are acceptable and NCCN lists irinotecan as a single agent. It also lists combinations, see p. COL-C of the NCCN guideline for colon cancer. NCCN has a complex schema when to give what for second line and also lists irinnotecan or Folfiri with Erbitux, Zaltrap or Vectbix. However, it does not list irinotecan with Xeloda.

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Afinitor for colon cancer

M Levin, MD — Fri, 21 Sep 2012 18:08:24 +0000

Afinitor is a new exciting drug that is approved for breast and kidney cancer and other conditions. Evidence for using Afinitor for colorectal cancer is weak – one small trial with weak results. There is some evidence from this trial ( Altomare et al) reported in ASCO 2012 that some colorectal cancer patients whose tumors had gotten worse on all standard treatments can benefit from a combination of Afinitor® (everolimus) and Avastin® (bevacizumab). This was a small trial in 50 patients. It showed a tumor control rate of 47%. Median progression-free survival time was 2.28 months, median overall survival time was 7.87 months. 46 percent of patients had disease control that lasted a median of 6.1 months. There were no complete or partial responses. 8 had a minor response lasting median 4.1 months. 15 had stable disease lasting median 6.7 months.

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Posttreatment surveillance after hepatic metastases resection for colorectal cancer

M Levin, MD — Fri, 24 Aug 2012 19:54:24 +0000

Since the appearance of effective new drugs for colorectal cancer and more aggressive surgical approaches to resecting isolated metastases, many patients who had metastatic cancer are now free of disease for an extended period of time. There are few guidelines on how to follow such patients it is fairly new situation and there are no mature studies. For high risk non-metastatic colon cancer, NCCN guidelines recommend annual CT of chest, abdomen and pelvis. Post-surgery surveillance is similarly warranted following resection of isolated colorectal cancer metastases because a minority of the recurrent patients can be treated with metastatectomy from the liver and lung, and some of them will enjoy long-term survival and even cure. The liver is the only site of recurrence in approximately 35 to 40 percent. Five-year survival rates up to 43 percent are reported following repeat liver resection for a second recurrence, with acceptable morbidity and perioperative mortality. Clearly, these patients need to be followed so as to intervene early after new metastases appear.

The impact of CT-based follow-up for the detection of resectable disease recurrence was addressed in a review of 705 patients who underwent resection of isolated colorectal cancer liver metastases at a single institution over a 14-year period. All were followed with a similar surveillance protocol, which included outpatient clinical examinations at 3, 6, 12, 18, and 24 months, and annually thereafter, with measurement of CEA and CA 19-9 levels at each visit. In addition, all patients had CT of the thorax, abdomen and pelvis every three months for the first two years, at six monthly intervals for three more years, then annually from year six to ten.

Of the 444 patients with a recurrence diagnosed on a surveillance CT, 404 were detected within two years. The site of recurrent disease was liver only in 36 percent, outside of the liver only in 38 percent, and both in the liver and in other organs in 26 percent. The authors did not report how many recurrences were detected by serum tumor markers versus CT scans.

In total, recurrent disease was treated surgically in 124 patients. At every time point (within one year of original surgery, one to two years, beyond two years), those patients treated by liver and/or lung resection had significantly better median survival than did those who received palliative chemotherapy alone. The mean number of scans performed per resectable recurrence was 35.3, and the cost per life-year gained was £2883, a value that compares favorably to other cost-effectiveness ratios that are considered acceptable in the US and elsewhere. UPTODate recommends the following surveillance strategy for patients with stage IV disease who are rendered surgically NED (no evidence of disease):

CEA every three months for two years, then every six months for three to five years

CT of the chest/abdomen and pelvis every three to six months for two years, then every 6 to 12 months up to a total of five years
Colonoscopy in one year; if no advanced adenoma repeat in three years, then every five years; if advanced adenoma is found, repeat in one year

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Zaltrap: A new drug for colon cancer

M Levin, MD — Fri, 24 Aug 2012 16:57:15 +0000

Zaltrap was approved by the FDA in the beginning of August 2012. It is also known as aflibercept, VEGF trap or, when used for macular degeneration, Eylea. By binding to and inhibiting vessel growth(angiogenic) growth factors, aflibercept inhibits tumor vessel production and supply.

Aflibercept has demonstrated efficacy in treating metastatic colorectal cancer in a recent randomized Phase III trial. The approval for colon cancer was based on a phase III trial. ZALTRAP, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is indicated for patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin-containing regimen.

Ith hs not fared as well in ither cancertypes. Aflibercept failed its primary endpoint of overall survival in the Vital phase III trial for second-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), although it improved the secondary endpoint of progression-free survival. It is also in trials for prostate cancer.

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FAP and AFAP testing: Genetic colon cancer

M Levin, MD — Fri, 24 Aug 2012 13:48:34 +0000

A small proportion of colon and rectal cancers arise in individuals who have genetic mutations. Familial Adenomatous Polyposis(FAP) and AFAP are autosomal dominant disorders with 50% risk of inheritance and about 75–80% of individuals with these conditions have an affected parent. Autosomal dominant inheritance means that an offspring of an affected individual has a 50% risk of inheriting the altered APC gene.
Adenomas develop in approximately half of all patients with FAP by age 15, and in 95% by age 35. Without intervention, most individuals with FAP will develop colon or rectal cancer by the fourth decade of life. Thus, screening and intervention for at-risk persons is critical and typically begins at puberty (National Comprehensive Cancer Network® [NCCN®], 2012). AFAP is an attenuated variety of FAP. Evidence in the published, peer-reviewed scientific literature indicates that genetic testing for mutations in the APC gene is appropriate for a specific subset of individuals who have been identified as at high-risk for FAP or AFAP. Among the specialty organizations that have recognized the role of FAP and AFAP genetic testing are the American Gastroenterological Association (AGA), American College of Medical Genetics (ACMG), NCCN and National Cancer Institute (NCI). It is generally accepted that genetic testing for FAP and AFAP is appropriate for the following purposes:
• to confirm the diagnosis of FAP and AFAP in an affected patient
• to provide predictive testing for at-risk relatives of AFAP and FAP-affected patients with known APC gene mutation.
MYH-Associated Polyposis (MAP), also known as MUTYH-associated polyposis, is a recently described syndrome that is related to FAP and that is also characterized by adenomatous polyps. It is, however, an autosomal-recessive syndrome, in which half of the affected individuals are carriers of the disease but are not affected, unless they receive one gene from each parent.

American College of Medical Genetics (ACMG) and the American Society of Human Genetics (ASHG) and American Gastroenterological Association (AGA) also offer guidelines. For genetic counseling and testing for adenomatous polyposis syndromes, including FAP, and AFAP, the guidelines include the following (NCCN, 2012):
• FAP Inclusion criteria include:
Presence of over 100 polyps, or fewer polyps at younger ages, especially in family known to have FAP
Autosomal dominant inheritance
Possible associated additional findings, including:
o Congenital hypertrophy of retinal pigment epithelium (CHRPE)
o Osteomas, supernumerary teeth, odontomas
o Desmoids, epidermoid cysts
o Duodenal and other small bowel adenomas
o Gastric fundic(body) gland polyps
increased risk of medulobastoma, papillary carcinoma of the thyroid (<2%) or hepatobalstoma (usually ?age 5 years)
Pancreatic cancers (<1%)
Gastric cancers (<1%)
• AFAP inclusion criteria include:
Fewer than 100 adenomas (range 0 – >1000) (average of 30 polyps)
Frequent right-sided distribution of polyps
Adenomas and cancers at age older than classic FAP (i.e., mean cancer age greater than 50)
Upper GI findings and thyroid cancer risk is similar to classic FAP
?Other extraintestinal manifestations, including CHRPE and desmoids are rare
• If personal history is positive, then refer to genetic screening
• If family mutation is known, then refer at-risk family members to genetic screening
For genetic counseling and testing for MAP, the guidelines include the following (NCCN, 2012):
• MAP inclusion criteria include:

Polyposis or colon cancers consistent with autosomal recessive (i.e., parents unaffected, siblings affected)
Fewer than 100 adenomas (range 0–100s and uncommonly >1000)
Adenomas and colorectal cancer at age older than classical FAP (median age >50)
Duodenal adenomas are uncommon
Attenuated polyposis with negative APC gene mutation

• If personal history is positive, then refer to genetic screening
• Testing for APC gene mutations usually precedes testing for MYH mutations, except in families in which only siblings are affected
• Recommend genetic counseling and testing for germ line MYH mutations for siblings of affected patients
• If family mutation is known, then refer at-risk family members to genetic screening

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