Docetaxel, a paclitaxel antitumor drug known as Taxotere, was approved in 1995 and was initially used to treat breast and non-small cell lung cancers.
As clinical studies progressed, docetaxel was also found to be effective in advanced prostate cancer, and in 2004, the FDA approved docetaxel for first-line chemotherapy in castration-resistant prostate cancer (CRPC).
What is docetaxel?
Docetaxel is a drug synthesized on the basis of chemicals from the leaves of the European yew tree. Its mechanism of action is to enhance microtubule protein aggregation and inhibit microtubule depolymerization, leading to the formation of stable nonfunctional microtubule bundles that cause cancer cells to arrest and apoptosis in the G2/M phase, thereby disrupting tumor cell mitosis.
Docetaxel is administered by intravenous drip at a dose of 75 mg/m per dose over 1 hour. A 3-week regimen of chemotherapy in combination with oral prednisone (5 mg twice daily, days 1-21) is usually used.
To prevent fluid retention, oral dexamethasone is routinely given for 3 consecutive days at 16 mg per day, with the first day of use to be taken 1 day before the Tysodi titration.
It is important to note that dexamethasone tablets are 0.75 mg/tablet, so a total of about 21 tablets per day can be taken in 2-3 oral doses.
Docetaxel chemotherapy regimen significantly improves survival in patients with advanced disease
Inevitably, chemotherapy for advanced prostate cancer has gone through a fumbling phase, with studies of chemotherapy with other agents (such as mitoxantrone) starting in the 1980s showing an efficiency of less than 10% and an average survival time (overall survival) of only 6 to 10 months.
This situation was finally improved in 2004, precisely because docetaxel demonstrated significant efficacy in clinical use, resulting in significantly longer overall survival in patients with mCRPC. The therapeutic benefit has also been demonstrated in the Chinese population.
TAX-327 study
The results of the docetaxel pivotal clinical study TAX-327, which enrolled 1006 patients with mCRPC, showed that patients receiving a 3-week regimen of docetaxel had 2.4 months longer overall survival compared with mitoxantrone (18.9 months vs. 16.5 months), and patients with a ≥50% decrease in prostate-specific antigen (PSA) were more likely to be treated with docetaxel. More patients had a ≥50% reduction (45% vs 32%) and a higher proportion of patients achieved pain relief (35% vs 22%).
SWOG-9916 study
Another pivotal study, SWOG-9916, which evaluated docetaxel in combination with estradiol mustard versus mitoxantrone in combination with prednisone, showed that docetaxel prolonged patient survival by almost 2 months compared with the control group (17.5 months vs 15.6 months).
In both of these trials, patients in the docetaxel-treated group had an average overall survival of 17.5 to 18.9 months, which means that docetaxel-based chemotherapy regimens extended the overall survival of patients with advanced prostate cancer by an average of 8 to 12 months compared with only 6 to 10 months with earlier chemotherapy regimens, which is a remarkable improvement.
How many cycles of chemotherapy does docetaxel require?
This question also varies from person to person. According to treatment guidelines, the current more uniform opinion is as follows:
- For hormone-sensitive prostate cancer with more metastases, especially with visceral metastases (e.g., liver, lung), docetaxel chemotherapy is usually used for at least 6 cycles;
- For CRPC, docetaxel chemotherapy is usually administered for at least 10 cycles.
In fact, current research in prostate cancer suggests that the use of more cycles can further improve patient prognosis. Therefore, more aggressive therapy remains acceptable as long as the patient is generally well tolerated, tolerates the adverse effects of chemotherapy, and the disease is not progressing (effective or stable).
The PSA needs to be reviewed regularly during chemotherapy as well as imaging (e.g., MRI), and also in conjunction with the patient’s subjective symptoms. In clinical practice, “effective chemotherapy” has been defined as a decrease in PSA of ≥50% from baseline after 4 cycles of chemotherapy and no progression of imaging changes according to response evaluation criteria in solid tumors (RECIST). ) without progression.
What are the common adverse effects of docetaxel?
- Bone marrow suppression. Neutropenia is the most common adverse reaction and is usually more severe. Therefore, blood tests should be performed before the start of a new chemotherapy cycle and after the end of a cycle of chemotherapy.
- Allergic reactions. May occur in a subset of cases, manifesting as hypotension or bronchospasm, and requiring interruption of therapy in severe cases.
- Skin reactions. Often manifests as erythema and rash on the body surface, sometimes with scratching, which can recover with symptomatic treatment.
- Fluid retention. This includes edema and, in rare cases, pleural effusion, ascites, pericardial effusion, increased capillary permeability, and weight gain have been reported.
- Gastrointestinal reactions. Nausea, vomiting, or diarrhea may occur.
- Neurotoxicity. Peripheral neurotoxicity is predominant and requires attention.
- Cardiovascular adverse reactions are rare.
- Other adverse reactions include: alopecia, weakness, mucositis, arthralgia and muscle pain, hypotension, and injection site reactions.
What should I know about chemotherapy with docetaxel?
- Tesotec must be used under the supervision of a physician experienced in the use of cancer chemotherapy drugs.
- All patients need to be premedicated (glucocorticoids, such as dexamethasone tablets) before receiving Tysodicty to reduce the occurrence of fluid retention, except in cases where it is contraindicated.
- Neutropenia is the most common adverse effect and blood counts should be monitored frequently during Tysodi treatment.
- Anaphylactic reactions may occur during the first few minutes of tesotide initiation and require close monitoring by your healthcare provider during this time.
- Peripheral neurotoxicity may occur during treatment with Tysodi.
Does docetaxel treatment cost a lot? Can Medicare pay for it?
Does docetaxel (docetaxel) cost a lot?
Docetaxel (Tasutil) is now on the medical insurance list of many tertiary care hospitals at 20 mg/strips, priced at about $1500/strips, and most of the resident population is able to take advantage of the medical insurance benefits, with an out-of-pocket payment of about 30%-50%. This greatly reduces the financial burden on mCRPC patients.
For patients with mCRPC, docetaxel chemotherapy (75 mg/m, 3-week regimen) remains the standard first-line regimen for now. If disease progression occurs during or after docetaxel treatment and the patient is generally well with an appropriate life expectancy, cabazitaxel chemotherapy is recommended.
Of course new drugs that continue to emerge (e.g., abiraterone, enzalutamide, etc.) have efficacy in mCRPC, and the specific use of these new drugs should be considered in light of their high drug prices, and pharmacoeconomics is one of the issues to consider.
Cost-effectiveness analysis has been conducted in China and abroad, and the results showed that the cost-effectiveness ratio in the abiraterone group was significantly higher than that of docetaxel. The clinical recommendation is to use abiraterone acetate tablets for better-off patients and those over 80 years of age, and to use docetaxel injection if economic conditions do not allow.
What should I do if docetaxel chemotherapy is not working?
If docetaxel chemotherapy does not work, try treatment with abiraterone and enzalutamide; if the latter does not work again, try cabazitaxel chemotherapy, which can be effective in lowering PSA levels and improving symptoms and RECIST response. Studies have shown that cabazitaxel can be an effective agent after failure of docetaxel, abiraterone, and enzalutamide therapy.
For patients with advanced prostate cancer with limited survival, regardless of the treatment option, physicians should evaluate the patient’s physical status, concomitant disease, tumor characteristics, and communicate fully with the patient and his or her family to ultimately develop a treatment plan that maximizes the patient’s benefit.
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