Report provides final results of the TROPIC trial of cabazitaxel

Cabazitaxel (Jevtana®) has recently been approved in the USA for the treatment of men with castration-resistant prostate cancer who have progressive disease following treatment with standard first-line chemotherapy (docetaxel + prednisone).

An article just published in the Lancet has now published the full and final results of the multi-center, randomized, prospective, controlled, Phase III trial (the TROPIC trial) which compared cabazitaxel + prednisone to mitoxantrone + prednisone in this group of patients. The results of this trial provided the pivotal data supporting approval of cabazitaxel in the US. Most of the data reported in this paper have been previously presented at major oncology meetings.

The final report confirms that:

  • Cabazitaxel + prednisone was associated with a 2.8 month period of progression-free survival as compared to 1.4 months for mitoxantrone + prednisone.
  • Cabazitaxel + prednisone was associated with a 15.1 month median overall survival compared to 12.7 months for mitoxantrone + prednisone (an overall survival benefit of 2.4 months, which equates to a decreased hazard ratio [HR] for mortality of 0.70).
  • Cabazitaxel is associated with a range of potentially very significant side effects, including
    • Neutropenia (a low level of neutrophils, often associated with fever) in 94 percent of patients, with severe neutropenia in 82 percent
    • Leukopenia (a low level of white blood cells) in 96 percent of patients, with severe leukopenia in 68 percent
    • Anemia (a low level of red blood cells) in 97 percent of patients, with severe anemia in 11 percent
    • Thrombocytopenia ( low level of platelets) in 46 percent of patients, with severe thrombocytopenia in 4 percent
    • Diarrhea in 47 percent of patients, with severe diarrhea in 6 percent
  • 18/371 cabazitaxel patients (5 percent) died within 30 days of initial treatment
    • 7 patients died of complications associated with neutropenia.
    • 5 patients died of heart problems.
  • Many other side effects occurred in > 10 percent of patients, so this is by no means a “benign” drug.

There is little doubt that cabazitaxel therapy needs to be managed with a great deal of attention to associated risks of severe side effects of therapy. The full prescribing information for cabazitaxel should be studied with care, and — in addition to the side effects mentioned above and in this new paper by de Bono et al. — patients and their doctors need to be conscious of the risk for severe hypersensitivity to cabazitaxel, possibly including generalized rash/erythema, hypotension (low blood pressure) and bronchospasm (a sudden difficulty with breathing). All cabazitaxel patients are advised to receive an appropriate pre-medication regimen of an antihistamine, a corticosteroid such as dexamethasone, and an H2 antagonist such as ranitidine.

In summary, while cabazitaxel does indeed offer a potential survival benefit for patients who have prostate cancer disease progression after treatment with docetaxel-based chemotherapy, this survival benefit comes with significant clinical risks, and each individual patient is advised to make careful decisions about the risk/benefit equation in conjunction with their physician. The “New” Prostate Cancer InfoLink further suggests that, because of its side effects,  a drug like cabazitaxel is probably best administered at a highly experienced chemotherapy infusion center under the oversight of experienced oncology nursing staff and a medical oncologist or hematologist/oncologist who has significant expertise in the management of advanced forms of prostate cancer.

One Response

  1. Somewhat makes one wonder if these drugs that appear to be able to extend one’s life for less than a year are worth the drastic reduction in the quality of life the patient is already experiencing. We all want to “live,” and our caregivers and family and friends want us to live, but they, and we, have to come to grips with that point in our living when it is pointless to drag out the inevitable and suffer even more while doing so.

    When I, personally, look at the cost of some of these drugs, and the expensive copay that will be required even if health insurance will pay a majority, when it comes my time, I do not want to burden my wife or whomever I have named in my will with that reduction in what will be coming to them with my demise. Please take note, that is MY opinion.

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