#docetaxel

In a recent randomized clinical trial, the PRESIDE Trial, Enzalutamide (Xtandi) showed that chemotherapy with docetaxel (Docetaxel) not only improved survival in men with metastatic castration-resistant prostate cancer (mCRPC), it sometimes reversed enzalutamide resistance. 

 PRESIDE was a randomized clinical trial that treated 687 men with mCRPC across 123 European sites. All the men were administered enzalutamide in addition to hormone therapy (ADT). After 13 weeks, 271 men had an increase in their PSA and/or an increase in tumor size based on scans. At this point, they were randomly assigned to have either: 

 A. Triplet therapy, combining enzalutamide, docetaxel, and ADT, or

B. Docetaxel, ADT, and placebo. 

 The men receiving the triplet therapy outperformed those receiving only docetaxel plus ADT in progression-free survival. This finding indicates that the enzalutamide was still efficacious for those who were also receiving ADT and docetaxel. The difference was modest but statistically significant. 

 Both experimental groups had similar treatment-related side effects, primarily caused by the chemotherapy, docetaxel. However, the triplet group experienced more significant incidents (49% vs 39%). 

 A similar randomized trial (ABIDO) used abiraterone along with ADT and chemotherapy as an alternate triplet therapy. Data showed that this triplet had considerably worse toxicity, particularly causing neutropenia, the presence of abnormally few white blood cells in the blood leading to an increased susceptibility to infection. 

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Astellas Pharma S.p.A. ha annunciato che AIFA ha riconosciuto la rimborsabilità di un’ulteriore indicazione per la somministrazione una volta al giorno della terapia orale enzalutamide negli uomini adulti con cancro della prostata metastatico sensibile agli ormoni (mHSPC, conosciuto anche come carcinoma prostatico metastatico sensibile alla castrazione o mCSPC). Gli uomini che ricevono una…

Chemotherapy has a bad reputation, but is it as bad as many of us expect? Are all chemotherapies the same? Do they all come with the same level of side effects? The answer to these questions is probably not and no.  

When we hear the word chemotherapy, the most natural response is that it will be terrible, it will lead to all types of nasty side effects and the total disintegration of a person’s quality of life. There is no denying that chemotherapy has side effects, but like all other advanced prostate cancer treatments, the side effects can differ from one man to the next.

At Cancer ABCs, we see men who do stop chemotherapy or have a dose reduction because the side effects become intolerable. Still, we also see this in many men who use primary ADT and the new, more advanced second-generation hormone manipulation drugs like Zytiga, Xtandi, Apalutamide, and Darolutamide.   

Quality of life (QoL) is important; for many of us, QoL is more important than its length.  

 Prostate cancer treatment currently has two (2) different chemotherapy drugs approved by the FDA; docetaxel (Taxotere) and cabazitaxel (Jevtana). Taxotere was approved before Jevtana so it is often given before Jevtana. However, over time there has been some thinking out of the box; what has been asked is, what if we gave Jevtana before Taxotere?

Examining this question was an abstract (abstract 5017) at the most recent ASCO virtual meeting. The abstract reported the final results from the randomized CABADOC trial. Patient preference was evaluated between Jevtna and Taxotere for first-line chemotherapy in men with metastatic castrate-resistant prostate cancer (mCRPC). The abstract was authored by: G Baciarello, R Delva, G Gravis, et al

The CABADOC Trial was a randomized study of 195 men who had not had any chemotherapy. It asked whether patients prefer Taxotere or Jevtana since both treatments have very similar clinical outcomes. The study was conducted in 17 different centers.

The study concluded that significantly more men preferred Jevtana compared with Taxotere (43% vs 27%), whereas 30% of the men had no preference. The most common factors influencing preferences were fatigue, pain, hair loss, and patient-defined life quality. There was a slightly reduced incidence of diarrhea in the first 3-month period in men receiving G-CSF and Jevtana (32.1% vs 24.3%) but not in men receiving docetaxel (23.8% vs 25%). Median progression-free and overall survival were similar in both groups.

There has been historical evidence showing that in men with metastatic castration-resistant prostate cancer (mCRPC) when Taxane based chemotherapy like docetaxel or cabazitaxel is given along with a platinum chemotherapy drug, there is increased positive activity. This activity has not been evaluated in any randomized trial. 

A study, reported in the Lancet, evaluated whether adding Carboplatin (a platinum drug) to cabazitaxel would improve outcomes.

The study involved a phase 1–2, open-label, randomized study in men with progressing metastatic castration-resistant prostate cancer. 

In the phase 1 part of the study, the subject men were given intravenous cabazitaxel and intravenous Carboplatin. All of the participating men received growth factor support and oral prednisone 10 mg daily. The primary endpoints of this phase 1 study were to determine the maximum tolerated dose of the combination. The phase 2 involved evaluating investigator-assessed progression-free survival. This trial is registered at ClinicalTrials.gov, number NCT01505868.

The study period ran between Aug 17, 2012, and May 11, 2015. In the phase 1 study, nine men completed as planned. In the phase 2 trial, one hundred and sixty (160) men were randomly assigned to receive either cabazitaxel (n=79) or cabazitaxel plus Carboplatin (n=81). 

During phase I, grade 3 adverse events were anemia (n=2), fatigue (n=1), thrombocytopenia (n=1), hypomagnesaemia (n=1), diarrhea (n=1), hypokalemia (n=1), anorexia (n=1), and dehydration (n=1), and no grade 4 adverse events occurred. 

No dose-limiting toxicities were observed.  

In the phase 2 study, the most common grade 3–5 adverse events were fatigue (7 [9%] of 79 in the cabazitaxel group vs 16 [20%] of 81 in the combination group), anemia (3 [4%] vs 19 [23%]), neutropenia (3 [4%] vs 13 [16%]), and thrombocytopenia (1 [1%] vs 11 [14%]). There were no treatment-related deaths.

A maximum tolerated dose of cabazitaxel of 25 mg/m 2 and Carboplatin of AUC 4 mg/mL per min was selected for phase 2. At a median follow-up of 31 months, the combination improved the median progression-free survival (PFS) from 4.5 months to 7.3 months. 

The study concluded that adding Carboplatin to cabazitaxel showed improved clinical efficacy compared with cabazitaxel alone for men with metastatic castration-resistant prostate cancer. Although adverse events were more common with the combination, the treatment was safe and generally well-tolerated.