title: Lack of Cumulative Toxicity Associated With Cabazitaxel Use in Prostate Cancer.
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 neutropenia 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 odds of having G3 to 4 neutropenia (OR = 0.90; 95% CI: 0.86-0.93; P < 0.01), febrile neutropenia (OR = 0.52; 95% CI: 0.34-0.81; P < 0.01) and G3 to 4 anemia (OR = 0.93; 95% CI: 0.86-1; P = 0.07). Patients with a body surface area >2 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.
authors.affiliation: From the Department of Clinical Medicine, Federico II University, Naples (GDL, LP, DB, SDP, CB); Department of Oncology, Medical Oncology Unit, San Donato Hospital, Arezzo (SB); Department of Oncohematology, University Hospital of Parma, Parma (DG); Policlinico Hospital, Bari (AG); Ospedale Papa Giovanni Paolo XXIII Hospital, Bergamo (CM); Medical Oncology Unit, Istituto Oncologico Veneto-IRCCS, Padua (VZ); Medical Affairs Oncology Division, Sanofi, Milan, Italy (DD); Department of Medicine, Urologic Oncology, Division of Hematology & Oncology, University of Alabama at Birmingham, Birmingham, AL (GS); and Department of Emergency and Organ Transplantation, Urology, Andrology and Kidney Transplantation Unit, University of Bari, Bari, Italy (GL).
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Lorenzo
authors.forename: Sergio
authors.initials: S
authors.lastname: Bracarda
authors.forename: Donatello
authors.initials: D
authors.lastname: Gasparro
authors.forename: Angela
authors.initials: A
authors.lastname: Gernone
authors.forename: Caterina
authors.initials: C
authors.lastname: Messina
authors.forename: Vittorina
authors.initials: V
authors.lastname: Zagonel
authors.forename: Livio
authors.initials: L
authors.lastname: Puglia
authors.forename: Davide
authors.initials: D
authors.lastname: Bosso
authors.forename: Davide
authors.initials: D
authors.lastname: Dondi
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lucarelli
authors.forename: Sabino
authors.initials: S
authors.lastname: De Placido
authors.forename: Carlo
authors.initials: C
authors.lastname: Buonerba
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D012189:Retrospective Studies; D043823:Taxoids / Q000009:adverse effects*
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; C552428:cabazitaxel