Phase II Study of Weekly Cabazitaxel for Advanced Prostate Cancer in "Unfit" Hormone-Refractory Patients Previously Treated With Docetaxel
The efficacy of three-weekly cabazitaxel is accompanied by an appreciable rate of serious
side effects and toxic deaths. The toxicity rates observed, including grade III-IV
neutropenia, febrile neutropenia and diarrhea, could be an obstacle to the use and
management of a drug that, on the other hand, has demonstrated great activity. In the
treatment of patients with prostate cancer, who have a larger number of morbidities than
patients with breast cancer, we assume the risk that in the transition from clinical trial
to clinical practice the drug will not be used much because of the risk of side effects,
cost, the discomfort derived from the routine use of G-CSF and the lack of patient
compliance with this type of regimens.
Rates of neuropathy, nail and conjunctive toxicity with this new taxane are not relevant,
which suggests that weekly administration will not produce relevant toxicity problems.
Weekly administration of other taxanes improved hematologic tolerance along with a better
therapeutic range in some cases, increasing the dose intensity and activity without
increasing the associated toxicity.
Phase I study has been reported studying weekly administration of cabazitaxel, recommended
dose is 10 mg/m2, administered on days 1, 8, 15 and 22 every 5 weeks in a 1-hour infusion,
being diarrhea the dose-limiting toxicity observed in this study.
Given the pharmacokinetic characteristics of this taxane and its activity and toxicity
profile, cabazitaxel might be a good candidate for studying in a weekly administration
regimen in patients with prostate cancer with a greater risk of toxicity associated with
treatment every 3 weeks, such as patients who have received previous pelvic radiation
therapy that affects more than 25% of the bone marrow reserve, patients over 75 years with a
worse performance status (ECOG 2) or who have already experienced important hematologic
toxicity in the previous treatment with docetaxel.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Time to progression by PSA at week 12, according to the PCCTWG II criteria.
Time to progression by PSA at week 12. PSA progression defined as an increase of ≥25% over nadir PSA concentration provided that the increase in the absolute PSA value was ≥5 μg/L for men with no PSA response, or ≥50% over nadir for PSA responders and PSA responders defined as a reduction in serum PSA concentration of ≥50% in patients with a baseline value of ≥20 μg/L.
Miguel A Climent, MD
FUNDACIÓN INSTITUTO VALENCIANO DE ONCOLOGÍA, Servicio de Oncología Médica, Profesor Beltrán Báguena, 11, 8 y 19, Valencia, 46009
Spain: Agencia Española de Medicamentos y Productos Sanitarios