Tuesday, June 20, 2006

Living With Chemotherapy: Tips From A Survivor

Chemotherapy is a word that strikes fear into most of our hearts. We've seen the movies and heard such horrible stories about undergoing this difficult treatment for a disease that could very well kill us. I underwent chemo for breast cancer and know that, in some cases, the cancer isn't hard … it isn't painful … it doesn't make us sick. That's the case for most of us who have breast cancer, but don't have distant metastases. But then, they say we need to do chemo and we know we'll feel that.

Although chemo drugs haven't changed that much, and they're still terribly hard on our bodies, the management drugs have changed a lot. Chemotherapy, for many of us, isn't the show-stopper we thought it would be. Of course, each of us is different and the chemo drugs affect each of us in different ways, but, for the most part, chemo is definitely doable.

My breast cancer was Stage IIIa, with a 5.8 cm tumor, 8 of 10 lymph nodes positive, and I was only 39 years old. That bought me a ticket for the chemo ride. And I was scared out of my wits. But, I found an online breast cancer support group, at WebMD, and those women told me everything to expect and more. I went through four rounds of adriamycin and cytoxan. Both of them are some pretty stout breast cancer chemo drugs. After that, I did a controversial treatment that involved extremely high doses of cytoxan, taxol, and cisplatin, so I learned quite a bit about surviving chemotherapy.

First of all, I would highly recommend getting a port. This is a line that goes into a vein in your chest, the entrance to which sits just under your skin, right below your collarbone. It requires a quick surgery to put it in but, if you're having a mastectomy for your breast cancer, you can get the chemo port put in at the same time. If you choose not to do that, you'll have to get your chemo treatments through your veins and chemo is really hard on your veins. This means that you will, most likely, have to endure multiple attempts for them to find a vein, as time goes by. With the port, it's already in a vein, so all they have to do is stick the needle into the port to access it. If you find this uncomfortable, there is a cream they can give you called Emla cream. One of the first things I learned was to tell them the moment I was uncomfortable. It's all fixable. You'll put the Emla cream on a bit before you have to have your port accessed and it'll numb your skin.

Most breast cancer chemotherapy drugs will cause your hair to fall out. This is because chemo kills the rapidly dividing cells in your body. Your mucous areas and hair follicles are affected for this reason. That's why you may have nausea or develop mouth or throat sores. Again, all this sounds scary, but is totally manageable. Since you will probably be losing your hair, which can be quite traumatic, I would advise going wig or hat shopping before you even get your first chemo. Take a girlfriend with you and be adventurous. Try on different styles, and even colors. If you've always wanted to be a blonde, now's your chance! Make a day of it and have fun with it. Goodness knows, you have to look for that silver lining every chance you get. Also, make sure to have your nausea med prescription filled before you go so you'll have it waiting for you if you need it at home. You may be pretty tired, afterward, so don't wait till then to get those meds.

On your first chemo day, they will probably give you some steroids, intravenously or through your port, to help with the nausea. This may make you hungry; it sure did for me! But, I would recommend you don't eat your favorite food on chemo day. Chemo is manageable, but after you're all done, you may find that you have associations. For example, I used to love the cucumber melon fragrance when I was going through chemo. I had cucumber melon everything! But, to this day, the smell of cucumber melon makes my stomach do a little somersault because it reminds me of such an unpleasant time in my life. The same can happen with food. I still can't look a chicken burrito in the eye! But, I'm sure glad I didn't eat a taco because I would've hated for that to be ruined for me!

Many breast cancer chemo drugs are hard on your bladder, so be sure to drink, drink, drink. If you don't feel like drinking water, then broth, jello, or even popsicles will help. Since you've gotten your nausea meds all filled in advance, be sure to take them as prescribed, whether you think you need them or not. Chemo nausea isn't just any kind of nausea and it's much easier to stay ahead of it than to try to fix it once it occurs. If you do happen to get nauseated, and I can't stress this enough, call your doctor!!! There are many, many nausea meds and you do not have to feel sick just because you're doing chemo. Once they find the right drug for you, it will be so much easier. So, do not suffer this in silence! The same applies for if you get sores in your mouth or throat.

You will be tired from this treatment. Most of us get more tired as the treatments progress because they make our white blood cell counts drop really low. Because of this, it's a good idea to keep some Purell, or something similar, with you all the time for use when you've had to touch, for example, public restroom door handles. Your risk of infection will be much higher during this time.

If you lose your hair, it will typically happen in 10-14 days after your first chemo treatment. If you have long hair, you might want to cut it short in preparation. I know I felt so out of control of everything, during that time. When your hair comes out, it lets go quickly and in large clumps, getting all over your pillow and clogging your drain. For many women, that is more traumatic than even losing a breast. So, I figured that was the one thing I could control about this whole breast cancer thing … when my hair came out. I cut it really short, beforehand and, when it started to let go, I had my husband get the clippers and shave my head. My daughter helped and we did a little Mohawk and stripe action first!

That was my way of shaking my fist at this cancer … it might take my breasts, and it might take my hair for a while, but I beat it to the punch! It was my way of saying, "You cannot take my spirit!" You can do the same thing. Your breast cancer does not define you. It is but a speed bump in the course of your life. Strap on your gloves and step into the ring. This chemo is your biggest punch. Your spirit is your own and that breast cancer can't touch it!

Melissa Buhmeyer is a breast cancer survivor and has been so for seven years. She is also the founder of http://www.breastcancer-treatment.us , a site focusing on breast cancer treatment options, news, articles, and survivor experiences.

Sunday, November 06, 2005

Chemotherapy Gave Us A Gift of Time

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Chemotherapy Gave Us A Gift of Time


By Lorraine Kember


In December 1999, my beloved husband of 32 years was diagnosed with pleural mesothelioma and given a prognosis of 3 to 9 months. He was a former Wittenoom child who at the tender age of seven lived in Wittenoom for period of seven short months. Tragically it was long enough for him to inhale the deadly blue asbestos dust that would ultimately take his life.

As Brian’s disease progressed, the tumor pressed against his esophagus making it almost impossible for him to swallow. For a short period of time, dilatation was given to stretch the opening, thereby enabling him to manage a pureed diet. However when these dilations were no longer successful, we were told that chemotherapy was the only option. It was painfully obvious that unless chemotherapy could shrink the tumor, Brian’s death would be imminent.

Although we had no choice, the thought of chemotherapy was frightening. We had heard stories of extreme nausea and hair loss, and the added fear of the unknown intensified our suffering. There were many questions. How would it affect us? Would it work? How long will it go on? Will Brian ever be able to eat normally again?

For Brian, chemotherapy was never promised as a cure but as a trial, offered to him in the hope of shrinking the tumor, thereby enabling him to eat and drink and hopefully, to afford him “quality of life” for the remainder of his life.

Brian began chemotherapy in January 2001; his reaction to the first round of treatment was dramatic; he vomited continuously and was unable to retain his oral medication and needed to be hospitalized. Unable He remained in hospital for a short time during which the Pain Management Specialist attached to the Palliative Care Unit was able to bring his symptoms under control. The medication he prescribed effectively controlled Brian’s nausea and when taken prior to further chemotherapy sessions, prevented further bouts of nausea from occurring.

Without fear of side effects, Brian welcomed his chemotherapy sessions and the resulting benefits of the treatment soon became obvious. By the end of the second round of chemotherapy it was obvious that the treatment had shrunk the tumor; the changes in his condition and disposition were amazing; he felt and looked so much better, was able to eat meat and enjoy food again. I could not get over the change in him.

Excerpt from my diary:

March 2001

Brian is feeling so much better. He is able to eat meat and enjoy food again. Chemotherapy HAS shrunk the tumor. I cannot get over the change in him. It is a precious gift and I am so grateful for it. Brian has been amazing. The chemo and nausea medication tire him for a bit but within a few days he is back on top and his general well-being is amazing. Oh the joy of seeing him able to eat again! The chemo has definitely given him better quality of life. His appetite is amazing!

I realized at this time that despite all of our fears regarding chemotherapy, it had worked well for us. It had given us a precious gift of time. A special “time out” from the pain and suffering of it all. There was quality of life and we were determined to live it to the full.

Excerpt from my diary


There’s laughter now in our days for we have grown stronger. We have learned to push our grief away and to live each moment of every single day, for we know that tomorrow may never come and that our goodnight may well be our goodbye...

Article written by: Lorraine Kember – Author of “Lean on Me” Cancer through a Carer’s Eyes. Lorraine’s book is written from her experience of caring for her dying husband in the hope of helping others. It includes insight and discussion on: Anticipatory Grief, Understanding and identifying pain, Pain Management and Symptom Control, Chemotherapy, Palliative Care, Quality of Life and dying at home. It also features excerpts and poems from her personal diary. Highly recommended by the Cancer Council. “Lean on Me” is not available in bookstores - For detailed information, Doctor’s recommendations, Reviews, Book Excerpts and Ordering Facility - visit her website http://www.cancerthroughacarerseyes.jkwh.com

Article Source: http://EzineArticles.com/










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Tuesday, November 01, 2005

Are Obese Women Getting Short-Changed By Chemotherapy Treatments?

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Are Obese Women Getting Short-Changed By Chemotherapy Treatments?


By Naweko San-Joyz

How much chemotherapy does an obese woman need? Typically an obese woman with breast cancer would receive reduced doses of chemotherapy as they battle breast cancer.

Back in June of 2005, a study published in the Archives of Internal Medicine concluded that obese women should receive chemotherapy based on their actual weight, and not in reduced as amounts as it the standard practice.

And now again a study presented in the August 2005 edition of Lancet claims that doctors should not reduce chemotherapy doses for obese women when no receptors for the hormone oestrogen have been found on the breast cancer cells. This type of cancer is called oestrogen-receptor negative.

Clinicians often reduce chemotherapy doses for obese patients because of worries about how the treatment may react with the patient and affect their overall health.

According to the study’s director Marco Colleoni of the European Institute of Oncology, Italy, and his colleagues, reducing the first course of chemotherapy for obese patients with oestrogen-receptor negative breast cancer proves “detrimental”.

Colleoni and his team looked at the relation between body-mass index (BMI), chemotherapy dose reduction, oestrogen receptor expression, and outcome for pre-menopausal women with breast cancer by examining data from four randomized trials.

They found that 97 out of 249 obese patients received less than 85% of protocol specified dose during the first course of chemotherapy compared with patients with normal and intermediate BMI.

Obese patients with oestrogen-receptor negative disease that received 85% or more of the first protocol specified dose had significantly better disease-free survival and overall survival than those who received less than 85% of the normally recommended dosage.

Yet, obese patients with oestrogen-receptor positive breast cancer who had reduced doses of chemotherapy did not have a significant difference in their outcome compared with those given the recommended chemotherapy doses.

And contrary to popular practice, the researchers also noticed that obese patients initially treated with protocol doses of chemotherapy did not have more toxicity than patients who received reduced doses.

Dr Marco Colleoni concluded that, “Our findings suggest that for women with ER-absent or ER-low tumours, reduction in chemotherapy dose should be avoided.”

The message for obese women coping with cancer is to be aware of your risks and rights. Ask your doctor will she recommend lower doses of chemotherapy for you based on your weight and ask why.

Resources: Lancet, Archives of Internal Medicine

Health author and Stanford University graduate Naweko San-Joyz lovingly writes from her home in San Diego. Her works include Acne Messages: Crack the Code of Your Zits and Say Goodbye to Acne (ISBN: 0974912204) and Skinny Fat Chicks, Why We’re Still Not Getting This Dieting Thing (ISBN: 0974912212). Naweko created the Noixia philosophy to help people enhance their lives by connecting with their inner-mysteries and inner-selves. Her works take often over-looked, yet viable research and transforms in into practical tools that people can use to improve their health. Get useful, but too often ignored women’s health news by visiting http://www.Noixia.com, Where Beauty Means Health.

Article Source: http://EzineArticles.com/










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Sunday, October 16, 2005

4 Steps for You to Help Yourself During Chemotherapy

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4 Steps for You to Help Yourself During Chemotherapy
By David Saunders

Chemotherapy is a word that causes dread in most who hear it. It is a time of stress as well as risk. If you, or someone you know, are facing chemotherapy, these four simple steps may help get through the process with better spirits and better results as well.

1. Tell your doctor if you get side effects from treatment

You can't expect the possibility of relief from side effects if you do not share them with your doctor. Be sure to communicate with your doctor. Some people keep a health journal during and after treatment to improve the information you have to present to your doctor if problems arise more gradually. Discuss what you might keep in a health journal that might improve the effectiveness of your treatment.

2. Ask your doctor before you take any other medicine

All drugs operate by manipulating some normal cell function. This includes the chemotherapy drugs as well. These manipulations may conflict with the intended effects of your chemotherapy treatment. Even herbals, or an over the counter pain reliever can lead to unintended consequences. Always inform your doctor before taking any other medications.

3. Take care of your health

There are many things you can do to support the natural ability of your body to restore, protect and defend itself from the effects of injury and disease. Seek to improve your diet, find ways to reduce other sources of stress in your life and be thankful for the hope and opportunity you have because of your treatment. These things can have a remarkable affect on your body and your feeling of good health.

4. Talk about your feelings

These are stressful times. Don't keep your feelings bottled up. People you know and love are probably feeling stress too. Help each other by being open about what you are going through. By being open with others, you can feel more in control of the stress and trepidation you’re feeling, instead of those things being in control of you.

Self-help can never take the place of professional health care. Ask your doctor and nurse any questions you may have about chemotherapy. Also don't hesitate to tell them about any side effects you may have. They want and need to know.

Dave Saunders is a professional lecturer, and certified nutritional educator. He enjoys creating interconnections through his writings and lectures to help others create context and see new discoveries and technologies in more a practical light. You can find out more about new discoveries in cancer research at http://www.cancerresearchnewsonline.com

Article Source: http://EzineArticles.com/










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Wednesday, October 12, 2005

How to Avoid Weight Gain During Chemotherapy

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How to Avoid Weight Gain During Chemotherapy


By Doug Grant

For Patsy M., the cancer was bad enough.

Then came the chemo and her energy level took a dramatic tumble while her once trim figure ballooned.

She tried watching what she ate. Cut down on portions. Nothing helped. The weight kept climbing.

When she asked her doctor she was told to exercise. It was the best answer to chemo weight-gain.

This wasn’t what she wanted to hear. She didn’t feel like exercising. Some days it was all she could do to move from bed to couch.

Then a friend told her about a neighbor who was going through chemo as if it was a Sunday school picnic. She continued shopping, visiting friends AND EXERCISING. Claimed it had to do with taking some simple sugars called glyconutritionals.

"Sounds like one of those whiz-bang miracle things, if you ask me," Patsy replied. "You see them advertised all the time and most of them don’t have a stitch of healing in them."

Her friend nodded, "I agree, except glyconutritional is a scientific name not a brand name. And my neighbor claims there is a ton of medical research behind them. Not to mention a few Nobel Peace Awards in Medicine and a thousand or more medical journal reports?"

"If that’s true, how come my doctor never told me about these simple sugars?"

"Because he might not have heard about them. Doctors have a hard enough time keeping up with developments in their own field without getting into food and food supplements. Although my neighbor did say that many doctors have begun incorporating the simple sugars into their practice."

"So what’s it supposed to do for me?"

"Help create more energy so you’ll feel more like doing what your doctor told you to do...exercise."

Patsy still looked doubtful. "Why can’t I just eat an energy bar?"

"Wrong kind of sugars. They will do you more harm than good. According to my neighbor, these eight simple sugars go directly to your body cells. It has something to do with building and strengthening your cell’s communication system. This in turn enables your cells to order in whatever they need to make repairs and stay healthy."

Patsy still wasn’t convinced. "And that’s supposed to give me more energy?"

"Well, actually the simple sugars do a whole lot more than help create energy. But wouldn’t that alone be a blessing? You might feel good enough to start exercising and working off some of that bulge peeking over the top of your jeans."

Patsy glared at her friend. "Well, thank you very much. I can always count on you to make me feel good about myself. So where do I get these simple sugars?"

"I don’t really remember. As I recall, my neighbor said there was only one company making a true and all-natural blend of the simple sugars. But I don’t remember the name. I think it started with an ‘M’."

"That’s real helpful. Maybe you ought to worry less about the bulge around my middle and find yourself some brain food. Now, if you’ll excuse me, I’m worn out with all this energy and exercise talk. I think I’ll go lie down."

More information about simple sugars and how they can help reduce chemo side-effects, can be found at http://www.GrantForHealth.com/chemopg.html

Article Source: http://EzineArticles.com/








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Sunday, October 02, 2005

What Is Chemotherapy And How Does It Work?

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What Is Chemotherapy And How Does It Work?

From the American Cancer Society



Chemotherapy is the use of medicines (or drugs) to treat disease. We sometimes call this type of treatment just "chemo." Although surgery and radiation therapy destroy or damage cancer cells in a specific area, chemotherapy works throughout the body. Chemotherapy drugs can destroy cancer cells that have metastasized or spread to parts of the body far from the primary (original) tumor.

More than 100 chemotherapy drugs are used in various combinations. Although a single chemotherapy drug can be used to treat cancer, generally they are more powerful when used with other drugs. Your chemotherapy treatment probably will consist of more than one drug. This is called combination chemotherapy. A combination of drugs with different actions can work together to kill more cancer cells and reduce the chance that you may become resistant to a particular chemotherapy drug.

You and your doctor will decide which drug or combination of drugs, dosages, way it will be given, and frequency and length of treatment are best for you. All of these decisions will depend on the type of cancer, its location, the extent of its growth, how it is affecting your normal body functions, and your general health.

A Checklist of Questions to Ask Your Doctor or Nurse

Before choosing chemotherapy as a treatment option, you should understand the expected benefits, side effects, and risks. Consider asking your doctor or nurse the following questions. In fact, take these questions with you to your next appointment. Our information, along with the information you receive from your doctor, should provide you with what you need to know about your treatment and give you realistic expectations about the outcome.

What is the goal of chemotherapy for my cancer?
What are the chances that the chemotherapy will work?
After chemotherapy, will I be cured, in remission, or relieved of my symptoms?
Are there other ways to achieve the same goals?
How will I know if the chemotherapy is working?
If the chemotherapy doesn't work are there other treatments for me?
What are the potential risks and side effects of the anticancer drug(s) I will be taking? How do the side effects of this chemotherapy compare with side effects of other treatments?
How will I receive chemotherapy, how often, and for how long? Where will I be given the drugs?
Are there ways to help me prepare for treatment and decrease the chances of side effects?
Will my diet be restricted in any way? My activities? My work? Exercise? Sexual activities?
Will I be treated with surgery, radiation, or both? If so, when and why? What are the expected results of each type of treatment?
If chemotherapy is to follow surgery or radiation, will it destroy any remaining cancer cells? Could chemotherapy be used alone?
Are there any clinical trials I could take part in?
How much will chemotherapy cost and will it be covered by my insurance or health plan? If the insurance company requests a second opinion, or if I would like one, whom do you suggest I see?

Here are some tips for remembering your doctor's answers:

Take notes during your appointments. Don't feel shy about asking your doctor to slow down if you need more time to write.
If you can, use a tape recorder during your visit so you won't miss a thing.
Consider taking a friend or relative to your appointment to help you understand what your doctor says during your visit and to refresh your memory afterward.
Always ask your doctor, nurse, and pharmacist as many questions as you want. If you don't understand their answers, keep asking until you do. Keep a "running list" and write down each new question as it occurs to you.

We may be able to answer many of your questions. Please call us at 1-(800)-ACS-2345 or click on the "Contact Us" button at the top of the screen.

Last Reviewed: 2003









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Chemotherapy

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Chemotherapy
From Wikipedia, the free encyclopedia.
Chemotherapy is the use of chemical substances to treat disease. In its modern-day use, it refers almost exclusively to cytostatic drugs used to treat cancer.

In its non-oncological use, the term may also refer to antibiotics (antibacterial chemotherapy). In that sense, the first modern chemotherapeutic agent was Paul Ehrlich's arsphenamine, an arsenic compound discovered in 1909 and used to treat syphilis. This was later followed by sulfonamides discovered by Domagk and penicillin G discovered by Alexander Fleming.

Other uses of cytostatic chemotherapy agents (including the ones mentioned below) are the treatment of autoimmune diseases and the suppression of transplant rejections (see immunosuppression and DMARDs).

Contents [hide]
1 History
2 Principles
3 Types and dosage
3.1 Alkylating agents
3.2 Anti-metabolites
3.3 Plant alkaloids
3.3.1 Vinca alkaloids
3.3.2 Podophyllotoxin
3.3.3 Taxanes
3.4 Topoisomerase inhibitors
3.5 Antitumour antibiotics
3.6 Hormonal therapy
4 Delivery
5 Treatment schemes
6 Side-effects
7 See also
8 References
9 External links




History
Main article: history of cancer chemotherapy
The era of chemotherapy began in the 1940s with the first uses of nitrogen mustards and folic acid inhibitors. Cancer drug development since then has exploded into a multi-billion dollar industry. The targeted-therapy revolution has arrived, but the principles and limitations of chemotherapy discovered by the early researchers still apply.


Principles
Cancer is the uncontrolled growth of cells due to damage to DNA (mutations) and, occasionally, due to an inherited propensity to develop certain tumours. Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body - in other words, the body attacks its own cells. In a contrast, transplant rejection happens because a normal healthy human immune system can distinguish foreign tissues and attempts to destroy them. Also the reverse situation, called graft-versus-host disease, may take place.

Broadly, most chemotherapeutic drugs work by impairing mitosis (cell division), effectively targeting fast-dividing cells. As these drugs cause damage to cells they are termed cytotoxic. Some drugs cause cells to undergo apoptosis (so-called "cell suicide").

Unfortunately, scientists have yet to be able to locate specific features of malignant and immune cells that would make them uniquely targetable (barring some recent examples, such as the Philadelphia chromosome as targeted by imatinib). This means that other fast dividing cells such those responsible for hair growth and for replacement of the intestinal epithelium (lining) are also affected. However, some drugs have a better side-effect profile than others, enabling doctors to adjust treatment regimens to the advantage of patients in certain situations.

As chemotherapy affects cell division, tumours with high growth fractions (such as acute myelogenous leukemia and the lymphomas, including Hodgkin's disease) are more sensitive to chemotherapy, as a larger proportion of the targeted cells are undergoing cell division at any time.

Chemotherapeutic drugs affect "younger" tumours (i.e. less differentiated) more effectively, because at a higher grade of differentiation, the propensity to growth usually decreases. Near the center of some solid tumours, cell division has effectively ceased, making them insensitive to chemotherapy. Another problem with solid tumours is the fact that the chemotherapeutic agent often does not reach the core of the tumour. Solutions to this problem include radiation therapy (both brachytherapy and teletherapy) and surgery.


Types and dosage
The majority of chemotherapeutic drugs can be divided in to: alkylating agents, antimetabolites, plant alkaloids, topoisomerase inhibitors, and antitumour agents. All of these drugs affect cell division or DNA synthesis and function in some way.

Some newer agents don't directly interfere with DNA. These include the new tyrosine kinase inhibitor imatinib mesylate (Gleevec® or Glivec®), which directly targets a molecular abnormality in certain types of cancer (chronic myelogenous leukemia, gastrointestinal stromal tumors).

In addition, some drugs may be used which modulate tumour cell behaviour without directly attacking those cells. Hormone treatments fall into this category of adjuvant therapies.

Dosage of chemotherapy can be difficult: if the dose is too low, it will be ineffective against the tumor, while at excessive doses the toxicity (side-effects, neutropenia) will be intolerable to the patient. This has led to the formation of detailed "dosing schemes" in most hospitals, which give guidance on the correct dose and adjustment in case of toxicity. In immunotherapy, they are in principle used in smaller dosages than in the treatment of malign diseases.

In most cases, the dose is adjusted for the patient's body surface area, a composite measure of weight and height that mathematically approximates the body volume. The BSA is usually calculated with a mathematical formula or a nomogram, rather than by direct measurement.


Alkylating agents
Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumour growth by cross-linking guanine nucleobases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. These drugs acts mainly nonspecifically, some of them requires conversion into active substances in vivo (e.g. cyclophosphamide).

Cyclophosphamide is one of the most potent immunosuppressive substances. In small dosages, it is very efficient in the therapy of systemic lupus erythematosus, autoimmune hemolytic anemias, Wegener's granulomatosis and other autoimmune diseases. High dosages cause pancytopenia and hemorrhagic cystitis. Other selected examples: cisplatin, carboplatin, ifosfamide, chlorambucil, busulfan, thiotepa, nitrosoureas and others.


Anti-metabolites
Anti-metabolites masquerade as purine ((azathioprine, mercaptopurine)) or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. They also affect RNA synthesis. Due to their efficiency, these drugs are the most widely used cytostatics. An important example is 5-fluorouracil (5FU), which inhibits thymidylate synthase. Fludarabine inhibits function of multiple DNA polymerases, DNA primase, DNA ligase I and is S phase-specific (since these enzymes are highly active during DNA replication).

Methotrexate, a folic acid analogue, prevents the formation of tetrahydrofolate, essential for purine and pyrimidine synthesis, by inhibiting dihydrofolate reductase. This leads to inhibited production of DNA, RNA and proteins (as tetrahydrofolate is also involved in the synthesis of amino acids serine and methionine).

Azathioprine is the main immunosuppressive cytotoxic substance. It is widely used in transplantations to control rejection reactions. It is nonenzymatically cleaved to 6-mercaptopurine that acts as a purine analogue and an inhibitor of DNA synthesis. By preventing the clonal expansion of lymphocytes in the induction phase of the immune response, it affects both the cell and the humoral immunity. It also successfully suppresses autoimmunity.


Plant alkaloids
These alkaloids are derived from plants and block cell division by preventing microtubule function. Microtubules are vital for cell division and without them it can not occur. The main examples are vinca alkaloids and taxanes.


Vinca alkaloids
Vinca alkaloids bind to specific sites on tubulin, inhibiting the assembly of tubulin into microtubules (M phase of the cell cycle). They are derived from the Madagascar periwinkle, Catharanthus roseus (formerly known as Vinca rosea). The vinca alkaloids include: -

Vincristine
Vinblastine
Vinorelbine
Vindesine

Podophyllotoxin
Podophyllotoxin is a plant-derived compound used to produce two other cytostatic drugs, etoposide and teniposide. They prevent the cell from entering the G1 phase (the start of DNA replication) and the replication of DNA (the S phase). The exact mechanism of its action still has to be elucidated.

The substance has been primarily obtained from the American mayapple (Podophyllum peltatum). Recently it has been discovered that a rare Himalayan Mayapple (Podophyllum hexandrum) contains it in a much greater quantity, but as the plant is endangered, its supply is limited. Studies have been conducted to isolate the genes involved in the substance's production, so that it could be obtained recombinantively.


Taxanes
Taxanes are derived from the Pacific yew tree, Taxus brevifolia. Taxanes enhance stability of microtubules, preventing the separation of chromosomes during anaphase. Taxanes include: -

Paclitaxel
Docetaxel

Topoisomerase inhibitors
Topoisomerases are essential enzymes that maintain the topology of DNA. Inhibition of type I or type II topoisomerases interferes with both transcription and replication of DNA by upsetting proper DNA supercoiling. Some type I topoisomerase inhibitors include camptothecins: irinotecan and topotecan. Examples of type II inhibitors include amsacrine, etoposide, etoposide phosphate, and teniposide. The latter are semisynthetic derivatives of epipodophyllotoxins, alkaloids naturally occurring in the root of mayapple (Podophyllum peltatum) .


Antitumour antibiotics
There are many differing antitumour antibiotics, but generally they prevent cell division by several ways: (1) binding to DNA through intercalation between two adjacent nucleotide bases and making it unable to separate, (2) inhibiting ribonucleic acid (RNA), preventing enzyme synthesis, (3) interfering with cell replication. They are products of various strains of the soil fungus Streptomyces. Examples are anthracyclines (doxorubicin, daunorubicin and epirubicin, which also inhibit topoisomerase II), actinomycin, bleomycin, mitomycin and plicamycin. Bleomycin acts in unique way through oxidation of a DNA-bleomycin-Fe(II) complex and forming free radicals, which induce damage and chromosomal aberrations. The most important immunosuppressant from this group is dactinomycin, which is used to in kidney transplantations.


Hormonal therapy
Several malignancies responds to hormonal therapy. Strictly speaking, this is not chemotherapy. Cancer arising from certain tissues, including the mammary and prostate glands, may be inhibited or stimulated by appropriate changes in hormone balance.

Steroids (often dexamethasone) can inhibit tumour growth or the associated edema (tissue swelling), and may cause regression of lymph node malignancies.
Prostate cancer is often sensitive to finasteride, an agent that blocks the peripheral conversion of testosterone to 5-hydroxy-testosterone.
Breast cancer cells often highly express the estrogen and/or progesterone receptor. Inhibiting the production (with aromatase inhibitors) or action (with tamoxifen) of these hormones can often be used as an adjunct to therapy.
Gonadotropin-releasing hormone agonists (GnRH), such as goserelin possess a paradoxic negative feedback effect followed by inhibition of the release of FSH (follicle-stimulating hormone) and LH (luteinizing hormone), when given continuously.
Some other tumours are also hormone dependent, although the specific mechanism is still unclear.


Delivery
Most chemotherapy is delivered intravenously, although there are a number of agents that can be administered orally (e.g. melphalan and gemcitabine). Depending on the patient, the cancer, the stage of cancer, the type of chemotherapy, and the dosage, IV chemotherapy may be given on either an inpatient or outpatient basis. For continuous, frequent or prolonged IV chemotherapy administration, various systems may be surgically inserted into the vasculature to maintain access. Commonly used systems are the Hickman line, the Port-a-Cath or the PICC line. These have a lower infection risk, are much less prone to phlebitis or extravasation, and abolish the need for repeated insertion of peripheral cannulae.


Treatment schemes
There are a number of strategies in the administration of chemotheraputic drugs used today. Chemotherapy may be given with a curative intent or it may aim to prolong life or to palliate symptoms.

Combined modality chemotherapy is the use of drugs with other cancer treatments, such as radiation therapy or surgery. Most cancers are now treated in this way. Combination chemotherapy is a similar practice which involves treating a patient with a number of different drugs simultaneously. The drugs differ in their mechanism and side effects. The biggest advantage is minimising the chances of resistance developing to any one agent.

In neoadjuvant chemotherapy (preoperative treatment) initial chemotherapy is aimed for shrinking the primary tumour, thereby rendering local therapy (surgery or radiotherapy) less destructive or more effective.

Adjuvant chemotherapy (postoperative treatment) can be used when there is little evidence of cancer present, but there is risk of recurrence. This can help reduce chances of resistance developing if the tumour does develop. It is also useful in killing any cancerous cells which have spread to other parts of the body. This is often effective as the newly growing tumours are fast-dividing, and therefore very susceptible.

Palliative chemotherapy is given without curative intent, but simply to decrease tumor load and increase life expectancy. For these regimens, a better toxicity profile is generally expected.

Most chemotherapy regimens require that the patient is capable to undergo the treatment. Performance status is often used as a measure to determine whether a patient can receive chemotherapy, or whether dose reduction is required.


Side-effects
The treatment can be physically exhausting for the patient. Current chemotheraputic techniques have a range of side effects mainly affecting the fast-dividing cells of the body. Important common side-effects include (dependent on the agent):

hair loss
nausea and vomiting
diarrhea or constipation
anaemia
depression of the immune system hence (potentially lethal) infections and sepsis
hemorrhage
secondary neoplasms
cardiotoxicity
hepatotoxicity
nephrotoxicity
ototoxicity
Virtually all chemotherapeutic regimens can cause depression of the immune system, often by paralysing the bone marrow and leading to a decrease of white blood cells, red blood cells and platelets. The latter two, when they occur, are improved with blood transfusion. Neutropenia (a decrease of the neutrophil granulocyte count below 0.5 x 109/litre) can be improved with synthetic G-CSF (granulocyte-colony stimulating factor, e.g. filgrastim, lenograstim, Neupogen®, Neulasta®.)

In very severe myelosuppression, which occurs in some regimens, almost all the bone marrow stem cells (cells which produce white and red blood cells) are destroyed, meaning allogenic or autologous bone marrow cell transplants are necessary. (In autologous BMTs, cells are removed from the patient before the treatment, multiplied and then re-injected afterwards; in allogenic BMTs the source is a donor.) However, some patients still develop diseases because of this interference with bone marrow.

Nausea and vomiting induced by chemotherapy can be alleviated with antiemetics. Usually metoclopramide, dexamethasone or 5 hydroxytryptamine 3 (5-HT3) receptor antagonists (dolasetron, granisetron, ondansetron) are used.

Some studies[1] and patient groups claim that the use of cannabinoids derived from marijuana during chemotherapy greatly reduces the associated nausea and vomiting, and enables the patient to eat. Some synthetic derivatives of the active substance in marijuana (tetrahydrocannabinol or THC) are in development for this indication.

In particularly large tumors, such as large lymphomas, some patients develop tumor lysis syndrome from the rapid breakdown of malignant cells. Although prophylaxis is available and is often initiated in patients with large tumors, this is a dangerous side-effect which can lead to death if left untreated.

Chemotherapy may increase the risk of cardiovascular disease and occasionally leads to secondary cancer.


See also
Cancer
Gene therapy
Experimental cancer treatments

References
^ Tramer MR, Carroll D, Campbell FA, Reynolds DJ, Moore RA, McQuay HJ. Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ 2001;323:16-21. PMID 11440936.

External links
Chemotherapy Regimens Database
Chemocare.com chemotherapy drug information
Retrieved from "http://en.wikipedia.org/wiki/Chemotherapy"










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