Diagnostic and Staging Information
Need to get PET Scan,
CEA, Surgical report and Pathology report. We also need to know more about the number and sizes of the liver lesions and the
venious involvement you described. Before chemotherapy, ask to get tested for the
KRAS gene mutation because it can affect which drugs you should be given. We know your cancer is advanced stage because of the lesions in the liver and abdomen.
The following also affect prognosis and we need to know the status to help make decisions. Differentiated histology, venous invasion of tumor and preoperative elevation of
CEA.
Carcinoembryonic Antigen (CEA Information)It is a complex
glycoprotein that is associated with the plasma membrane of tumor cells, from which it may be released into the blood.
The
CEA has been
sugested as having prognostic value for patients with colon cancer. Preoperative
CEA values have been positively correlated with stage and negatively correlated with disease free survival.
Although not satisfactory for screening a healthy population,
CEA has been used to monitor recurrence. Early data suggested that
CEA prededed clinical relapse by several months. Determinations of
CEA should be done frequently: at a minimum of every 3 months and if possible every 1 month to 2 months. Elevations above baseline should be verified rapidly to exclude laboratory error.
The
CEA is of some use as a monitor in treatment. Usually the
CEA returns to normal within 1 to 2 months of surgery, but if it returns elevated persistent disease may be indicated. The test is not infallible in patients treated with radiotherapy and chemotherapy but can be useful in those whose tumor is not measurable.
Chemo information with and without links:
Chemotherapy is used to reduce the likelihood of metastasis developing, shrink tumor size, or slow tumor growth. Chemotherapy is often applied after surgery (
adjuvant), before surgery (
neo-
adjuvant), or as the primary therapy (palliative). The treatments listed here have been shown in clinical trials to improve survival and/or reduce mortality rate and have been approved for use by the US Food and Drug Administration. In colon cancer, chemotherapy after surgery is usually only given if the cancer has spread to the lymph nodes (Stage III). At the 2008 annual meeting of the American Society of Clinical Oncology, researchers announced that
colorectal cancer patients that have a mutation in the
KRAS gene do not respond to certain therapies, those that inhibit the epidermal growth factor receptor (
EGFR)--namely
Erbitux (
cetuximab) and
Vectibix (
panitumumab). Following recommendations by
ASCO, patients should now be tested for the
KRAS gene mutation before being offered these
EGFR-inhibiting drugs.
Adjuvant (after surgery) chemotherapy. One regimen involves the combination of
infusional 5-fluorouracil,
leucovorin, and
oxaliplatin (
FOLFOX)
5-fluorouracil (5-
FU) or
Capecitabine (
Xeloda)
Leucovorin (
LV,
Folinic Acid)
Oxaliplatin (
Eloxatin)
Chemotherapy for metastatic disease. Commonly used first line
chemotherapy regimens involve the combination of
infusional 5-fluorouracil,
leucovorin, and
oxaliplatin (
FOLFOX) with
bevacizumab or
infusional 5-fluorouracil,
leucovorin, and
irinotecan (
FOLFIRI) with
bevacizumab 5-fluorouracil (5-
FU) or
Capecitabine UFT or
Tegafur-uracil
Leucovorin (
LV,
Folinic Acid)
Irinotecan (
Camptosar)
Oxaliplatin (
Eloxatin)
Bevacizumab (
Avastin)
More Chemotherapy Drug InformationCytotoxic chemotherapy drugs are taken up by dividing cells, including normal cells, such as those in the lining of the mouth, the bone marrow, the hair follicles, and the digestive system. A cytotoxic drug is often combined with others to increase the likelihood that all the cancer will be destroyed.The newer chemotherapy drug practice is called “targeted therapy”, in which the drugs attack cancer cells without destroying normal cells. These drugs are also called “
biologics.” Some targeted therapies focus on the internal components and function of the cancer cells. These therapeutic agents use small molecules that can get into the cancer cells and disrupt their function, thus causing the cancer cells to die.Other targeted therapies, including the monoclonal antibodies, focus on receptors on the outside or surface of the cancer cells. Still other targeted therapies, anti-
angiogenesis inhibitors, focus on preventing blood vessels supplying oxygen to the cancer cells, causing the cancer cells to starve and die. Biologic therapeutic agents seem to produce less severe side effects, compared to cytotoxic agents. Unfortunately, the present generation of
biologics is often not adequate to destroy all the cancer cells unless combined with
cytotoxics. The goal of research into
biologics at the moment is to find an effective combination of
biologics, without having to add
cytotoxics, to destroy the cancer.Because cytotoxic chemotherapy drugs cannot distinguish between cancerous cells and normal cells (especially the blood cells; the cells in the mouth, stomach, and bowel; and the hair follicles), side effects occur. Most normal cells will grow back and be healthy, but, during treatment, the patient may experience: low blood counts (
neutropenia, leading to infections; anemia, leading to fatigue; and low platelets, leading to bleeding); mouth sores caused by swelling of the mucous membrane (
stomatitis); nausea; vomiting; diarrhea; and/or hair loss. Each chemotherapy drug, or combination of drugs, has its own set of side effects.Research has shown that combination therapy enhances the strength of each anticancer drug administered. The regiment depends on the type of cancer being treated, the stage at which the cancer has progressed, the timing of the cell cycle, and the patient’s overall health.Other drugs, besides
cytotoxics and
biologics, are administered in conjunction with these chemotherapy agents to increase the effectiveness of the treatment. For example,
leucovorin,
citrovorum factor or
folinic acid (trade name calcium
leucovorin), is used with chemotherapy drugs, such as
fluorouracil and
methotrexate, to enhance anticancer effects or to prevent or lessen side effects, respectively.
CytotoxicsFluorouracil, 5-
fluorouracil or 5-
FU (trade name
Adrucil®): An
antimetabolite drug that attacks cells at specific phases in the cell cycle (cell-cycle specific).
Fluorouracil interferes with DNA synthesis and disrupts protein synthesis when also incorporated into RNA.
Fluorouracil is a pyrimidine antagonist.
Fluorouracil was developed nearly 40 years ago.There are numerous 5-
FU dosing schedules. In the
adjuvant setting, these include: bolus (rapid infusions) daily for five days every four weeks (the Mayo Clinic regimen); weekly for six out of every eight weeks (the Roswell Park regimen); and
infusional schedules. In the advanced disease setting, both weekly bolus and
infusional schedules have been used. The various regimens differ as to their toxicities. The bolus schedules tend to have greater bone marrow suppression and
mucositis, whereas the
infusional regimens (which require central venous access) cause more hand/foot syndrome. Overall, prolonged infusion schedules appear to be marginally more effective and less toxic.Side effects of 5-
FU include: diarrhea,
mucositis, hand/foot syndrome (plantar-
palmar erythema), and moderate bone marrow suppression.
Capecitabine (trade name
Xeloda®): An
antimetabolite drug that attacks cells at specific phases in the cell cycle (cell-cycle specific).
Capecitabine is the pill form of
fluorouracil and is a pyrimidine antagonist.The convenience of oral therapy and the prospect of avoiding long-term intravenous access complications, such as thrombosis and infections, have stimulated the development of oral
fluoropyrimidines.
Capecitabine, a
fluoropyrimidine carbamate that is converted to 5-
FU in tumor and normal tissues, is the most widely used. Twice-daily oral administration of
capecitabine simulates continuous infusion of 5-
FU without the costs and inconvenience of an infusion pump. Preclinical studies have shown that
capecitabine is an important component of targeted therapy because
capecitabine exhibits selectivity for tumor tissue.
Leucovorin (
LV), calcium
leucovorin,
citrovorum factor,
folinic acid:
Leucovorin is used in combination with other chemotherapy drugs, such as 5-
FU, to enhance effectiveness in treating advanced disease, or, as an antidote to the effects of drugs, such as
methotrexate.
Side effects of
leucovorin include: allergic reactions (rash, itching, facial flushing), and, rarely, nausea and vomiting.
Oxaliplatin (trade name
Eloxatin™): An
alkylating agent of the metal salt type that is most active in the resting phase of the cell (cell-cycle nonspecific).
Oxaliplatin was recently developed and approved by the FDA.
Oxaliplatin was initially approved as a second-line therapy with 5-
FU/
LV, but, studies established
FOLFOX as one of the preferred first-line regimens.
Oxaliplatin was recently approved for use in the
adjuvant setting after a study showed that patients who received
FOLFOX had improved, disease-free survival years later. Stage III patients derived more benefit than Stage II patients. Although no improvement in overall survival has been seen yet, this study established
FOLFOX as a solid option in the
adjuvant setting.Side effects of
oxaliplatin include: bone marrow suppression and, a sensory
neuropathy that is exacerbated by exposure to cold.
BiologicsBevacizumab (trade name
Avastin®): A monoclonal antibody, or
angiogenesis, drug that works by interfering with the process of
angiogenesis by targeting and inhibiting human vascular
endothelial growth factor (
VEGF).
Bevacizumab is used as part of a combination chemotherapy regimen.
Bevacizumab is FDA-approved for use with either
FOLFOX or
FOLFIRI (see below) as prescribed. Side effects include impaired wound healing and bleeding or clotting, so most medical practitioners wait at least four weeks after major surgery to administer it.In a randomized Phase II trial, adding low-dose
bevacizumab to weekly 5-
FU/
LV, in patients with advanced
colorectal cancer, improved the response rate, median time to progression, and, as a secondary endpoint, median survival. Two recently reported Phase III trials have confirmed these early positive findings, including the addition of
bevacizumab to
FOLFOX. Side effects of
bevacizumab include: reversible hypertension and
proteinuria, as well as rare serious side effects, such as gastrointestinal perforation, surgical wound
dehiscence (rupture), bleeding, and clotting.
Cetuximab, C225 (trade name
Erbitux™): A monoclonal antibody and signal transduction inhibitor that targets and binds to epidermal growth factor receptors (
EGFR) on the surface of the cell. By binding to these receptors,
cetuximab blocks an important pathway that promotes cell division, and causes
apoptosis (cell death).
Cetuximab is approved for use, typically as a third-line treatment, in chemotherapy-refractory disease (cancer that resists chemotherapy treatment) after
oxaliplatin and
irinotecan have failed.
Cetuximab works better when combined with
irinotecan, even after
irinotecan alone has failed.Side effects of
cetuximab include: an
acneiform rash over the face, chest, and back occurring in most patients; and, allergic reactions.
FOLFOX and FOLFIRIThe chemotherapy schedules known as
FOLFOX and
FOLFIRI are the
lynchpins of chemotherapy for advanced
colorectal cancer.
FOLFOX consists of
leucovorin (FOL),
fluorouracil (F), and
oxaliplatin (OX).
FOLFIRI consists of
leucovorin (FOL),
fluorouracil (F), and
irinotecan (
IRI).These are known as
infusional schedules because the
fluorouracil is given as an infusion over 22 to 46 hours after the other drugs are given as boluses (relatively rapid injections). Both schedules are given every two weeks. The infusion pump is usually disconnected at home by a home health care nurse, so only one visit every two weeks to the outpatient clinic is needed. Some patients even work full-time during chemotherapy.When faced with treating a patient with advanced
colorectal cancer in the first-line setting, doctors often question whether to start with
FOLFOX or
FOLFIRI. There is no direct evidence favoring one treatment over the other, although comparative trials are underway.Given the
neurotoxicity of
oxaliplatin, patients with preexisting
neuropathies, such as diabetes, should receive an
irinotecan-based treatment regimen instead. Patients who have underlying bowel dysfunction, which could be exacerbated by
irinotecan, should be started on an
oxaliplatin-based therapy. Patients with renal dysfunction may need to avoid
oxaliplatin, since the renal system is the principal route of elimination. Patients with liver dysfunction need to be wary of
irinotecan.
Multiple Targeted Therapies Not shown to be better:
For the study, Eli Lilly & Co.’s
Erbitux was added to standard treatment, which includes
Genentech Inc.’s
Avastin. Since both are “targeted” drugs and attack tumors in different ways, the thinking was that the combo would do a better job of keeping the cancer from growing.
But the results show “more is not always better,” said Dr. Robert Mayer, of Dana-
Farber Cancer Institute in Boston. He wrote an editorial published with the study in Thursday’s New England Journal of Medicine.
What makes the results even more compelling, Mayer said, is that another similar study reached the same conclusion. That study, released in December, tested another targeted drug that works the same way as
Erbitux.
“This is the first time we’
ve seen harm by combining targeted therapies and it tells us we need to be cautious,” said Dr. Jordan Berlin, a gastrointestinal cancer specialist at Vanderbilt-Ingram Cancer Center in Nashville, Tenn.
More about KRASThe
KRAS test, though, is expected to be very helpful in deciding when to use an
EGFR MAb. One reason to avoid giving
EGFR MAbs when a
KRAS mutation is present is to avoid unnecessary side effects. “About 85% of patients using
EGFR inhibitors develop a significant rash,” said Dr. Eng. While treatable with topical and oral antibiotic therapies, the rash represents a quality-of-life issue; it can be painful and
pruritic and can cause a patient to be self-conscious about his or her appearance.
A more dangerous side effect to be avoided is a severe allergic reaction. This occurs rarely in most patient groups—usually less than 5% of patients are affected.
Panitumumab, a second-generation
EGFR inhibitor under FDA review, should reduce the chance of allergic reaction in all patients to less than 1%. Still, the rash is expected to remain a problem with
panitumumab, as it occurs with all
EGFR inhibitors.
The high cost of anti-
EGFR therapy—about $10,000 a month—also makes it important to avoid treating patients who would derive no benefit. But perhaps most important of all, the time wasted on such therapy could be better used treating patients with therapies that have a possibility of producing a tumor response, such as
FOLFOX (a combination of
folinic acid [
leucovorin], 5-
fluorouracil [5-
FU], and
oxaliplatin) with
bevacizumab;
FOLFIRI with
bevacizumab; or
investigational VEGF inhibitors.
Liver metastasesAccording to the American Cancer Society statistics in 2006, over 20% of patients present with metastatic (stage IV)
colorectal cancer at the time of diagnosis, and up to 25% of this group will have isolated liver metastasis that is potentially
resectable. Lesions which undergo curative resection have demonstrated 5-year survival outcomes now exceeding 50%.
Resectability of a liver metastasis is determined using preoperative imaging studies (CT or MRI),
intraoperative ultrasound, and by direct palpation and visualization during resection. Lesions confined to the right lobe are amenable to en bloc removal with a right
hepatectomy (liver resection) surgery. Smaller lesions of the central or left liver lobe may sometimes be
resected in anatomic "segments", while large lesions of left hepatic lobe are
resected by a procedure called hepatic
trisegmentectomy. Treatment of lesions by smaller, non-anatomic "wedge" resections is associated with higher recurrence rates. Some lesions which are not initially amenable to surgical resection may become candidates if they have significant responses to preoperative chemotherapy or
immunotherapy regimens. Lesions which are not amenable to surgical resection for cure can be treated with modalities including radio-frequency ablation (
RFA),
cryoablation, and
chemoembolization.
Patients with colon cancer and metastatic disease to the liver may be treated in either a single surgery or in staged surgeries (with the colon tumor traditionally removed first) depending upon the fitness of the patient for prolonged surgery, the difficulty expected with the procedure with either the colon or liver resection, and the comfort of the surgery performing potentially complex hepatic surgery.
Therapy for Liver MetastisisSurgery is currently considered the "gold standard" treatment for stage IV patients having limited liver/lung metastases and is potentially curative (in about 1/3 of patients who are eligible for liver resection). Many patients are not eligible for this potentially curative surgery due to size/location of liver metastases. There are several new options for these patients detailed below, such as
Radiofrequency ablation, Hepatic Arterial Infusion Pump, and
Stereotactic Radioablation. Hepatic Arterial Infusion Pump (
HAI)
Go to Page Radiofrequency Ablation (
RFA)
Go to Page Stereotactic Radioablation/Conformal Radiotherapy
Go to Page Therasphere
Go to Page Intraperitoneal Chemotherapy
Go to Page The questions below are useful in engaging your Medical Oncologist about treatment options for metastatic colorectal cancer.
o Has the cancer spread to other parts of my body? If so, where?
o What are the treatment options available for my kind of cancer?
o How effective are these treatments?
o How are these treatments given?
o How long will I have to be on these treatments?
o How will I know if my treatment is working?
o Is there any way to lessen the side effects?
o Should I change my diet during treatment?
o Where can I go for more information and support?
o If I decide to receive adjuvant chemotherapy, what is my prognosis?
o If I decide not to receive adjuvant chemotherapy, what is my prognosis?
o Are there specialized tools that can help estimate survival based on my personal information?
o Given my diagnosis, what are the drug options and schedules of treatment?
o Are there any "high-risk" features of my tumor that make it more important for me to consider adjuvant therapy?
o Are there any medical factors related to my overall health that would make it harder for me to undergo adjuvant therapy?
o What are the side effects and other risks of the treatment regimen prescribed for me?
o Is there a clinical trial appropriate for my situation?
o Is there anything else I should know to help me make this decision?
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