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Docetaxel Side Effects Prostate Cancer

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Drugs Into Your Bloodstream

Docetaxel in Metastatic Prostate Cancer

You might have the treatment through a drip into your arm. Your nurse puts a small tube into one of your veins and connects the drip to it.

Or you might need a central line. This is a long plastic tube that gives the drugs into a large vein, either in your chest or through a vein in your arm. It stays in the whole time you are having treatment.

Each treatment takes about an hour and you have it once every 3 weeks.

Subcellular Fractionation And Western Blotting

Subcellular fractionation was performed using Subcellular fractionation was conducted using NE-PER Nuclear and Cytoplasmic Extraction Reagents according the manufacturers recommendations. Western blotting was performed. Briefly, the protein was separated by SDS-PAGE and transferred into nitrocellulose transfer membrane to further incubation with 5% milk in PBS/0.05% Tween20 for 1 h, the incubation for the membrane with the indicated antibody overnight at 4 °C, subsequently followed by incubation with a horseradish peroxidase secondary antibody for another 1 h at room temperature. Proteins were showed using an enhanced chemiluminescence .

What Drugs Interact With Taxotere

  • Docetaxel is a CYP3A4 substrate. In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant administration of compounds that induce, inhibit, or are metabolized by cytochrome P450 3A4.
  • In vivo studies showed that the exposure of docetaxel increased 2.2-fold when it was coadministered with ketoconazole, a potent inhibitor of CYP3A4.
  • Protease inhibitors, particularly ritonavir, may increase the exposure of docetaxel. Concomitant use of Taxotere and drugs that inhibit CYP3A4 may increase exposure to docetaxel and should be avoided.
  • In patients receiving treatment with Taxotere, close monitoring for toxicity and a Taxotere dose reduction could be considered if systemic administration of a potent CYP3A4 inhibitor cannot be avoided.

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Numbness Or Tingling In Fingers Or Toes

Numbness or tingling in fingers or toes is often temporary and can improve after you finish treatment. Tell your doctor if youâre finding it difficult to walk or complete fiddly tasks such as doing up buttons.

Nail changes

During treatment your nails may change colour. This gradually goes after treatment as your nails grow.

Your nail might separate from the nail bed and look white or yellow. The nail may eventually fall off but usually grows back.

Improving How Long Patients Live

Docetaxel

The ENZAMET trialfunded in part by the drugs manufacturer, Astellas Pharma, as well as government health agencies in Canada and Australiaenrolled more than 1,100 men with hormone-sensitive metastatic prostate cancer. The men were randomly assigned to ADT combined with enzalutamide or with any of three other androgen-blocking drugs.

At a median follow-up of nearly 3 years, men who received ADT plus enzalutamide had a 33% reduced risk of death, with 80% still alive compared with 72% of men treated with ADT plus another antiandrogen drug, reported the trials lead investigator, Christopher Sweeney, M.B.B.S., of the Dana-Farber Cancer Institute.

Men in the enzalutamide group also had better clinical progression-free survival , which the research team defined as the time until the return of disease-related symptoms, the detection of new metastases on imaging scans, or the initiation of another cancer treatment for prostate cancer, whichever came first. At 3 years, 63% of men in the enzalutamide group were alive without clinical progression of their disease, compared with 33% in the standard treatment group.

Although enzalutamide appeared to be effective regardless of whether men had high- or low-volume disease, one apparent differentiating factor was planned early treatment with docetaxel. Nearly half of the men in both treatment groups received early treatment with docetaxel and, for those men, enzalutamide was not associated with longer overall survival.

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Monitoring And Combination Use

Docetaxel is administered via a one-hour infusion every three weeks over ten or more cycles. Treatment is given under the supervision of an oncologist. Strict monitoring of blood cell counts, liver function, serum electrolytes, serum creatinine, heart function, oxygen saturation and fluid retention is required detect adverse reactions and toxicity so that treatment can be modified or terminated if necessary.

Premedication with corticosteroids is recommended before each administration of docetaxel to reduce fluid retention and hypersensitive reactions. Other medications will often be given to aid pain management and other symptoms. The treatment of breast cancer with doxorubicin and cyclophosphamide is enhanced by adjuvant treatment with docetaxel. Docetaxel is also used in combination with capecitabine, a DNA synthesis inhibitor.

What Are The Side Effects Of Docetaxel

You may have a life-threatening allergic reaction or a severe skin reaction. Get emergency medical help if you have signs of an allergic reaction: hives, burning eyes, skin pain, red or purple skin rash with blistering and peeling fever, sore throat, wheezing, chest tightness, trouble breathing feeling like you might pass out swelling of your face, lips, tongue, or throat.

You may have swelling in your intestines, which could cause death quickly. Call your doctor right away if you have stomach pain or tenderness, diarrhea, or fever.

Some side effects may occur during the injection. Tell your caregiver if you feel light-headed, or if you have trouble breathing or fast or irregular heartbeats.

Also call your doctor at once if you have:

Side effects may be more likely in older adults.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Common side effects may include:

  • allergic reactions
  • fingernail or toenail changes.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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Docetaxel In Pivotal Trials

Docetaxel was the first active cytotoxic treatment in mCRPC. Its approval in 2004 is based on 2 landmark phase III trials showing significant improvement in overall survival and quality of life . The SWOG 9916 trial is a phase III study of 770 mCRPC patients who were randomized to docetaxel and estramustine or mitoxantrone plus prednisone . The docetaxel arm achieved better OS and biochemical recurrence . The TAX 327 trial is a phase III study of 1,006 mCRPC patients who were randomized to receive docetaxel with prednisone or mitoxantrone with prednisone. In comparison to mitoxantrone, docetaxel yielded better OS , BR , and symptomatic relief . More than one third of the patients discontinued docetaxel after a maximum of 810 cycles without disease progression. Quality of life evaluation favored docetaxel for symptomatic control .

Questions To Ask Your Doctor Or Nurse

Docetaxel (Taxotere) for Progressive, Metastatic Prostate Cancer
  • How can chemotherapy help?
  • How long will the treatment last, and how many sessions will I need?
  • What are the possible side effects of chemotherapy, and how long will they last?
  • Can I stop the treatment if I find the side effects difficult to deal with?
  • Are there any other treatments available to me?
  • Who should I contact if I have any questions during my treatment and how do I contact them?
  • What happens if chemotherapy doesnt work? Are there other treatments I can have later on?
  • Are there any clinical trials I can take part in?

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Dr Claire Vale Who Presented The Data At Asco Said:

Research into new prostate cancer treatments can be incredibly expensive and can take a long time, so this type of analysis that makes the best use of the information we already have, can make a big difference.

Even then, its extremely rare to find such clear links between the characteristics of the patient and how effective their treatment is going to be. In this case, the evidence is clear, and we want to make sure its incorporated into clinical practice as soon as possible.

Docetaxel Use In High

The phase 3NRG Oncology/RTOG 0521 trial aimed toevaluate if there was any benefit to adding docetaxel chemotherapy tostandard treatment with long-term androgen suppression plus radiotherapy in men with prostate cancer considered to have high-risk disease withoutevidence of metastasis.1 Docetaxel had been routinely used in menwith metastatic castration-sensitive prostate cancer with improvements in overallsurvival , therefore, there was interest to study its impact in a differentsubgroup of men with prostate cancer.1

Thisinitial study led by Rosenthal and colleagues found that docetaxel improved OSfrom 89% to 93% 0.69 90% CI, 0.49 to 0.97 one-sided P = .034). There was also a decrease inthe 6-year rate of distant metastasis in the docetaxel group compared with the AS + RT-only group . Finally, thedocetaxel group had a higher 6-year disease-free survival rate of 65%compared with 55% in AS + RT . This study had a medianfollow-up of 5.7 years. Recently, new longer-term data from the same study witha median follow-up among survivors of 10.4 years was published by Sandler andcolleagues.2

Similarly,the cumulative incidence of distant metastasis was lower in the docetaxelCT + AS + CT group at 20% compared with theAS + RT only group at 22% , although this againwas not statistically significant . There was no statistical difference in the number ofpatient deaths between the 2 groups, and no new treatment-related grade 5toxicities were reported.

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Dr Following Progression In Mcspc

The activity of DR following progression in mCSPC is addressed in only one retrospective analysis of the GETUG-AFU trial . The first DR at the time of castration resistance achieved a BR of 20% and a median PSA-PFS of 4.1 months. In the first- or second-line setting, DR yielded a BR of 14% which did not correlate with PFI . The PSA-PFS in the second line was only 3.4 months. Overall, severe adverse events occurred in 16% in the first- and second-line treatment with DR .

Both CHAARTED and STAMPEDE reported that patients progressing to mCRPC received DR in 1423% of cases, but the efficacy outcomes in this subgroup have not been reported .

Treating Smarter Not Harder: Thousands Of Men Could Be Spared Side Effects Of Docetaxel Chemotherapy

What Is Docetaxel Chemotherapy

Results from an international study funded by Prostate Cancer UK could change the way we treat advanced prostate cancer, enabling healthcare teams to target those men who will benefit most from chemotherapy, and to reduce side effects in others.

A key part of our research strategy is developing better treatments. Often, this means developing new medicines that are more effective at treating prostate cancer.
But it also means finding better ways to use existing treatments, so that men with prostate cancer can live longer lives with fewer side effects.

As part of this work, and thanks to your support, weve invested more than £2.5m into researchers analysing the results of the STAMPEDE trial, which aims to find the best way to treat men with advanced prostate cancer .

Now, new analysis of STAMPEDE and two other trials has showed that some men with advanced prostate cancer benefit much more than others from the chemotherapy docetaxel.

Men with large prostate tumours, who also had many secondary tumours, were almost three times as likely to be alive after five years when given docetaxel chemotherapy alongside the usual hormone therapy.

Presented at the American Society of Clinical Oncology conference, the results pave the way for more personalised treatments, enabling healthcare teams to target docetaxel at those who will benefit the most, while moving others more quickly onto different treatments that will work for them.

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Possible Side Effects Of Chemotherapy

Chemo drugs attack cells that are dividing quickly, which is why they work against cancer cells. But other cells in the body, such as those in the bone marrow , the lining of the mouth and intestines, and the hair follicles, also divide quickly. These cells can also be affected by chemo, which can lead to side effects.

The side effects of chemo depend on the type and dose of drugs given and how long they are taken. Some common side effects can include:

These side effects usually go away once treatment is finished. There are often ways to lessen these side effects. For example, drugs can be given to help prevent or reduce nausea and vomiting.

Along with the risks above, some side effects are seen more often with certain chemo drugs. For example:

  • Docetaxel and cabazitaxel sometimes cause severe allergic reactions. Medicines are given before each treatment to help prevent this. These drugs can also damage nerves , which can cause numbness, tingling, or burning sensations in the hands or feet.
  • Mitoxantrone can, very rarely, cause leukemia several years later.
  • Estramustine carries an increased risk of blood clots.

If you notice any side effects while getting chemo report them to your cancer care team so that they can be treated promptly. In some cases, the doses of the chemo drugs may need to be reduced or treatment may need to be delayed or stopped to prevent the effects from getting worse.

Chemotherapy For Prostate Cancer

Chemotherapy refers to any type of therapy that uses chemicals to kill or halt the growth of cancer cells. While chemotherapy is unlikely to cure prostate cancer, it may provide some benefits to patients. For example, it may be used:

  • To relieve symptoms associated with very advanced or metastatic disease, improving the patients quality of life

  • To improve the outcome of prostate cancer surgery if administered for a short time after the procedure

  • To work in conjunction with hormone therapy and improve the patient outcome

  • To prolong the life of a prostate cancer patient who no longer responds to hormone therapy

  • To treat men with advanced prostate cancer who carry the AR-V7 gene variant

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Antiandrogens For Prostate Cancer

These prostate cancer drugs work by blocking the effect of testosterone in the body. Antiandrogens are sometimes used in addition to orchiectomy or LHRH analogs.This is due to the fact that the other forms of hormone therapy remove about 90% of testosterone circulating in the body. Antiandrogens may help block the remaining 10% of circulating testosterone. Using antiandrogens with another form of hormone therapy is called combined androgen blockade , or total androgen ablation. Antiandrogens may also be used to combat the symptoms of flare . Some doctors prescribe antiandrogens alone rather than with orchiectomy or LHRH analogs.

Available antiandrogens include abiraterone acetate , apalutamide , biclutamide , darolutamide , enzalutamide , flutamide , and nilutamide . Patients take antiandrogens as pills. Diarrhea is the primary side effect when antiandrogens are used as part of combination therapy. Less likely side effects include nausea, liver problems, and fatigue. When antiandrogens are used alone they may cause a reduction in sex drive and impotence.

Side Effects Of Chemotherapy

Dr. Agarwal on the Advantages of Docetaxel in Prostate Cancer

All chemotherapy drugs work in slightly different ways, making it challenging to predict side effects for individual patients. Dosages, drug combinations and drug responses will vary from patient to patient.

The American Cancer Society lists the following as the most common side effects of chemotherapy:

  • Increased risk of infections

  • Easy bruising or bleeding

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In Five Years A Major Treatment Shift

In men diagnosed with metastatic hormone-sensitive prostate cancer, the cancer is typically driven to grow and spread by androgens that are produced largely in the testes. For many years, treatments that block androgen production have been a mainstay for men initially diagnosed with metastatic prostate cancer.

Starting in 2014, that began to change after a large clinical trial showed that adding the chemotherapy drug docetaxel to ADT improved how long men with hormone-responsive disease lived. Shortly after, another clinical trial showed that adding abiraterone to ADT also improved survival in these men, although primarily in men with many metastatic tumors, known as high-volume disease.

However, docetaxel, which works by directly killing cancer cells, can have substantial side effects, and some patients arent healthy enough to tolerate it. And abirateronewhich blocks androgen production throughout the bodycan also cause side effects, including those that affect the liver. It also has to be given in combination with the steroid prednisone, which carries its own toxicity.

Doing so, Dr. Chi said during a presentation of the TITAN data at the ASCO meeting, might help stave off the typically inevitable development of hormone-resistant cancer, which is more difficult to treat and a key driver of prostate cancer deaths.

Discovery Regulation And Marketing

Docetaxel is marketed worldwide under the name Taxotere by Sanofi-Aventis as well as Docefrez by Sun Pharma Global and Zytax by Zydus. Annual sales of Taxotere in 2010 were 2.122 billion . The patent expired in 2010.

Taxotere was developed by Rhône-Poulenc Rorer following from the discoveries of Pierre Potier at CNRS at Gif-sur-Yvette during his work on improvements to the production of Taxol.

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Combination Radiation And Endocrine Therapy

Sometimes, patients receive hormone therapy in combination with external beam radiation therapy for the treatment of prostate cancer. This treatment uses a high-energy X-ray machine to direct radiation to the prostate tumor. For patients with intermediate or high risk prostate cancer, studies show this combination is more effective at slowing the disease than endocrine therapy or radiation therapy alone.

Radiation can also come in the form of a monthly intravenous drug called Xofigo. Xofigo is approved for use in men who have advanced prostate cancer that has spread only to the bones. Candidates should have also received therapy designed to lower testosterone. The drug works by binding to minerals within bones to deliver radiation directly to bone tumors. A study of 809 men showed that those taking Xofigo lived an average of 3 months longer than those taking a placebo.

Two other similar drugs are samarium-153 and strontium-89 .

Docetaxel Continues To Show Profound Benefits In Prostate Cancer

Docetaxel Injection at best price in Mumbai by CSC Pharmaceuticals ...

Targeted therapies and immunotherapy are revolutionizing oncology, however, chemotherapy retains a key role in the treatment of advanced prostate cancer, with recent data showing profound benefits with docetaxel in newly diagnosed patients.

William Oh, MD

Targeted therapies and immunotherapy are revolutionizing oncology, however, chemotherapy retains a key role in the treatment of advanced prostate cancer, with recent data showing profound benefits with docetaxel in newly diagnosed patients, according to William Oh, MD.

The recent positive findings seen with docetaxel come from 2 randomized trials: CHAARTED and STAMPEDE. In the largerSTAMPEDE trial, adding docetaxel to standard hormonal therapy significantly improved survival among men with newly diagnosed, hormone-naïve advanced prostate cancer. The median overall survival was 81 months with docetaxel plus standard of care versus 71 months with standard of care alone . In the CHAARTED study , the median OS was 57.6 months with the combination of docetaxel and androgen-deprivation therapy versus 44 months with ADT alone .

In an interview withTargeted Oncologyat the 2016 Chemotherapy Foundation Symposium, Oh, chief, Division of Hematology and Medical Oncology, professor of Medicine and Urology, Mount Sinai School of Medicine, discussed the continued significance of docetaxel in advanced prostate cancer.

TARGETED ONCOLOGY:Can you provide an overview of the role of docetaxel in metastatic prostate cancer?

References:

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