Treatment Side Effects


The side effects of the following drugs will vary from person to person. Some may have all and others none at all and others will experience 1 or 2, to varying degrees of severity. Again, if you find you are suffering from any of them, be sure to talk to your doctor or nurse about any side effects or concerns you have.

Click the drug name below to take you to the details;

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Interlukin-2

Interferon

Sutent

Nexavar

Avastin

Torisel

Afinitor

Votrient

Axitinib


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Interlukin-2

Common side effects:

With this drug, many people have a temporary drop in the number of blood cells made by the bone marrow, leading to the following side effects;

Some of these side effects can be life threatening, particularly infections. You should contact your doctor if you have any of these side effects. Your doctor will check your blood counts regularly to see how well your bone marrow is working

Other common side effects include:

Occasional side effects:

Some people may have one or more of the following side effects;

Rare side effects:

A very small number of people may have hair thinning - this is more likely to happen with long courses or high doses of Interlukin-2.

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Interferon

Common side effects:

With this drug, many people have a temporary drop in the number of blood cells made by the bone marrow, leading to the following side effects;

Some of these side effects can be life threatening, particularly infections. You should contact your doctor if you have any of these side effects. Your doctor will check your blood counts regularly to see how well your bone marrow is working

Other common side effects include:

Occasional side effects:

Some people have the following side effects;

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Sutent

Common side effects:

Patients who take SUTENT have these side effects more often than other side effects.

Possible serious side effects:

Rare, life-threatening events:

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Nexavar


Common side effects:

Possible serious side effects:

When to seek medical attention:

If any of the following signs or symptoms occur, you should seek medical attention right away:

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Avastin

Common side effects:

Common side effects that occurred in more than 10% of people who received Avastin for different cancer types were nosebleeds, headache, high blood pressure, inflammation of the nose, too much protein in the urine, taste change, dry skin, rectal bleeding, tear production disorder, back pain and inflammation of the skin (exfoliative dermatitis).

More serious side effects:

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Torisel

Before you begin treatment with TORISEL, your doctor may give you an antihistamine. It is possible to have a serious allergic reaction even after you receive an antihistamine. Tell your doctor or nurse if you are allergic to antihistamines or are unable to take antihistamines for any other medical reasons. Tell your doctor or nurse if you have any swelling around your face or difficulty breathing during or after treatment.

The most common side effects:

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Afinitor

Common side effects (occurring in greater than 30% of patients):

Less common side effects (occurring in 10-29% of patients):

Contact your health care provider immediately, day or night, if you should experience any of the following symptoms:

The following symptoms require medical attention, but are not an emergency. Contact your health care provider within 24 hours of noticing any of the following:

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Votrient

Common side effects:

Seek medical attention right away if any of these SEVERE side effects:


Axitinib

How Axitinib Works – the VEGF Pathway

Axitinib is a selective inhibitor of the VEGF Receptors 1, 2, and 3. VEGF is an acronym for “Vascular Endothelial Growth Factor.” VEGF is a protein molecule secreted by cells in the human body to signal to blood vessel cells to grow and divide. VEGF molecules travel through body fluid to connect with receptors on the surface of vascular cells. Their arrival triggers a cascade of signals within the cell that leads to the activation of genes that prevent the cell from dying. The VEGF pathway is important to all blood vessel growth, but it is of particular significance in tumor growth and angiogenesis. Through this pathway tumors grow blood vessels, which provide them with nutrients to continue growing.

Axitinib works by blocking the VEGF pathway, so blood vessels sprouted by tumors are never signaled to divide. Thus, theoretically, tumor growth can be limited or eliminated entirely. Essentially, axitinib combats tumors through attrition. The drug fits into the receptors that would normally house VEGF molecules, but does so without turning on protective genes that the normal VEGF signal would. As a result, the tumor’s vascular cells cannot proliferate and the tumor has a much harder time obtaining nutrients by which to grow. Alternatively, antibody drugs like bevacizumab work by targeting the VEGF signaling molecules themselves, binding to them in a way that makes them unable to bind to their receptors; so the growth signal is interrupted.

The VEGF pathway is targeted in part by several other anti-tumor drugs, including sunitinib (Sutent) and sorafenib (Nexavar). The dosage for axitinib in this trials was 5 mg given twice a day. By contrast, the standard dosage for the other targeted oral therapies are: sunitinib 50 mg/day, two weeks on one week off, and sorafenib 400 mg given twice a day continuously. Dr. Rixe speculates in his paper that the success of axitinib compared to these drugs may be a matter of depth versus breadth: whereas sunitinib and sorafenib target many pathways employed by growing tumors, axitinib focuses specifically on VEGFR, and delivers a more concentrated and powerful dose of medicine to that specific process of tumor growth.

Tumor necrosis was even noted in several study patients, even in some with progressive disease, a response that Dr. Rixe notes demands further consideration.

Adverse Events

Almost every patient, 48 of them, had a treatment-related adverse event. 28 had a grade 3 or grade 4 treatment-related adverse event.[4]

The most common side effects recorded in the trial were :-

Hypertension is a common side effect of anti-VEGF medications and was expected as a result of axitinib. It was recorded in 30 of the 53 patients tested, with 8 experiencing it at grades 3 or 4. However, in most patients hypertension was easily managed with one or more standard blood pressure medications and the trial was able to continue safely. After going off the drug, hypertension generally dissipated. Hematological toxicity – decreased production of blood cells or platelets that can occur as a result of many different cancer treatments – was not recorded. Overall, the toxicity from treatment with axitinib was well within safe levels and could easily be controlled with additional medication.

Diarrhea was associated with positive response to the treatment and non-responders generally recorded no increase in gastrointestinal distress. As patients acclimated to the drug, diarrhea generally stabilized. The point about the diarrhea aside, there was no data available to do analysis of which base line markers could be prognostic for patient response to treatment.

Discontinuance of Treatment

Patient accrual for this trial was conducted from October 2003 to April 2004. At the time of the report preparation, April 2007, 50 of the 52 patients were off treatment. 25 patients had progressive disease or had absence of efficacy, and another 10 were removed due to adverse events. Two were still on treatment with CRs.

Conclusions

The results reported in the study are encouraging. However, Dr. Rixe cautions that the drug’s apparent success could be the product in part of patient selection bias. Among the 52 patients enrolled in the study, 22 had no unfavorable prognostic risk factors[5] in addition to their illness. Further studies would benefit from a better representation of risk factors in patient samples.

Nevertheless, the results of Dr. Rixe’s phase II trial of axitinib are encouraging and warrants a Phase 3 trial.. Axitinib could become a powerful agent in the fight against renal-cell cancer, if not in achieving tumor regression then at least in contributing to patient stabilization

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