Lack of cumulative toxicity associated with cabazitaxel use in prostate cancer

Giuseppe Di Lorenzo, Sergio Bracarda, Donatello Gasparro, Angela Gernone, Caterina Messina, Vittorina Zagonel, Livio Puglia, Davide Bosso, Davide Dondi, Guru Sonpavde, Giuseppe Lucarelli, Sabino De Placido, Carlo Buonerba

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Abstract

Cabazitaxel provided a survival advantage compared with mitoxantrone in patients with castration-resistant prostate cancer refractory to docetaxel. Grade 3 to 4 (G3-4) neutropenia and febrile neu-tropenia were relatively frequent in the registrative XRP6258 Plus Prednisone Compared to Mitoxantrone Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer (TROPIC) trial, but their incidence was lower in the Expanded Access Program (EAP). Although cumulative doses of docetaxel are associated with neuropathy, the effect of cumulative doses of cabazitaxel is unknown. In this retrospective review of prospectively collected data, the authors assessed ''per cycle'' incidence and predictors of toxicity in the Italian cohort of the EAP, with a focus on the effect of cumulative doses of cabazitaxel. The study population consisted of 218 Italian patients enrolled in the cabazitaxel EAP. The influence of selected variables on the most relevant adverse events identified was assessed using a Generalized Estimating Equations model at univariate and multivariate analysis. ''Per cycle'' incidence of G 3 to 4 neutropenia was 8.7%, whereas febrile neutropenia was reported in 0.9% of cycles. All events of febrile neutropenia occurred during the first 3 cycles. Multivariate logistic regression analysis showed that higher prior dose of cabazitaxel was associated with decreased oddsofhavingG3to4neutropenia (OR=0.90; 95% CI: 0.86-0.93; P<0.01), febrile neutropenia (OR=0.52; 95% CI: 0.34-0.81; P2 m2 presented increased odds of having G 3 to 4 neutropenia (OR=0.93; 95% CI: 0.86-1; P= 0.07), but decreased odds of having G3 to 4 anemia. Among the toxicities assessed, the authors did not identify any that appeared to be associated with a higher number of cabazitaxel cycles delivered. Prior cumulative dose was associated with reduced G3 to 4 neutropenia and anemia. The apparent protective effect associated with higher doses of cabazitaxel is likely to be affected by early dose reduction and early toxicity-related treatment discontinuation. Because this analysis is limited by its retrospective design, prospective trials are required to assess the optimal duration of cabazitaxel treatment.

Original languageEnglish
Article numbere2299
JournalMedicine (United States)
Volume95
Issue number2
DOIs
Publication statusPublished - 2016

ASJC Scopus subject areas

  • Medicine(all)

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    Di Lorenzo, G., Bracarda, S., Gasparro, D., Gernone, A., Messina, C., Zagonel, V., Puglia, L., Bosso, D., Dondi, D., Sonpavde, G., Lucarelli, G., De Placido, S., & Buonerba, C. (2016). Lack of cumulative toxicity associated with cabazitaxel use in prostate cancer. Medicine (United States), 95(2), [e2299]. https://doi.org/10.1097/MD.0000000000002299