The importance of 3 weeks … before starting docetaxel along with ADT


A new study in BJU International has shown the importance of waiting at least 3 weeks after initiation of androgen deprivation therapy (ADT) until initiation of docetaxel chemotherapy in the treatment of men with newly diagnosed, metastatic, hormone-sensitive prostate cancer (mHSPC).

The value of combination ADT + docetaxel chemotherapy in treatment of newly diagnosed men with mHSPC and a significant number of metastases at time of diagnosis has been clearly shown in the CHAARTED and STAMPEDE trials in recent years. But what Rulach et al. have been able to show is just how important it is to wait at least 3 weeks between initiation of ADT and initiation of the chemotherapy when this type of treatment is being used out in the “real world” of clinical practice.

Any use of docetaxel is associated with a series of well-known and potentially serious side effects, including febrile neutropenia. “Neutropenia” is a condition that occurs when there is a serious reduction in the number of neutrophils (a type of white blood cell or leukocyte) in the bloodstream. Neutropenia reduces your ability to fight off bacterial infections. Febrile neutropenia occurs when a patient with neutropenia gets an infection that leads to a fever … and febrile neutropenia can be deadly. It is something that medical oncologists always watch out for in patients receiving certain type of chemotherapy (including docetaxel). Here in the US, many patients being treated with docetaxel will be given special drugs to lower the risk for neutopenia along with their chemotherapy — drugs like the granulocyte-colony stimulating factors or G-CSFs filgrastim (Neupogen) and pegfilgrastim (Neulasta).

Rulach et al. carried out a retrospective analysis of data from 270 recent, eligible patients, all newly diagnosed with mHSPC, and all treated at hospitals in the west of Scotland. Here are the basic data that they report:

  • Of the 270 patients with mHSPC who were hypothetically eligible for treatment for ADT + docetaxel chemotherapy,
    • 103 (38.1 percent) received docetaxel.
    • 167 (61.9 percent) did not.
  • Among the 103 patients treated with docetaxel,
    • 35/103 (34 percent) were hospitalized for any cause.
    • 17/103 (16.5 percent) had episodes of febrile neutropenia.
    • 2/103 (1.9% percent died within 30 days of chemotherapy.
    • The risk for febrile neutropenia was nine times greater if docetaxel chemotherapy was started within 3 weeks of ADT initiation.
  • Among the 167 patients not treated with docetaxel, compared to the patients who did get docetaxel treatment,
    • There was a significantly increased risk of prostate cancer progression (hazard ratio [HR] = 2.03).
    • There was a significantly increased risk of death for all causes (HR = 5.88).

The authors conclude very straightforwardly that:

Docetaxel chemotherapy in hormone-naïve [metastatic prostate cancer] has significant toxicities, but has a similar effect on time to progression and overall survival as seen in randomised trials. Chemotherapy should be started 3 weeks or more after androgen deprivation.

This is a critically important finding in terms of routine clinical practice. Basically, it says, “The combination of ADT + docetaxel works well in the ‘real world’ as well as in clinical trials — but don’t screw things up by starting the docetaxel too early. It takes the human body a little time to adapt to the ADT before you should start the chemotherapy.”

 

2 Responses

  1. ….. and what if either Neupogen or Neulasta is given concurrently with docetaxel without waiting 3 weeks? Does this mitigate the risk? Was this tested?

  2. Dear Rick:

    This was a retrospective data analysis. I can’t answer your question.

    As far as I know, no one has ever tested this, but I can tell you that (solely on the basis of personal knowledge at the current time) if I was diagnosed tomorrow with significant mHSPC, I would quite certainly wait for 3 weeks after starting ADT before I started docetaxel chemotherapy (whether I was getting Neupogen or Neulasta or not).

    I simply makes sense (to me) to let one’s body have a few weeks to adapt to the first biological “insult” before initiating the second one. And I know of no data that suggests better outcomes of ADT + docetaxel if one starts the docetaxel any earlier.

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