Background: Cabazitaxel (C), a novel taxane developed to overcome D resistance, showed an overall survival improvement after D in metastatic castration-resistant prostate cancer (mCRPC) in a three-weekly schedule. Its main toxicity is hematological, especially in unfit patients. We aimed to evaluate efficacy and safety of weekly C/prednisone (P) schedule in "unfit" mCRPC previously treated with D. Methods: Unfit pts defined as ECOG 2, dose reduction due to febrile neutropenia during D treatment or radiation therapy affecting more than 25% of bone marrow reserve, with mCRPC progressing after D treatment with adequate bone marrow, liver and kidney functions were included. C 10 mg/m2 was administered on days 1, 8, 15 and 22 of 5-week cycles with P (5 mg b.i.d.). Radiological and PSA response were evaluated according to the PCWG2 (Scher H, 2008) criteria and toxicity according NCI-CTC AE. Results: To date 70 pts have been enrolled and data are available for 66. Median age was 73 y (range 54-84), 67% pts had ECOG 2, 87% had bone, 14% liver and 11% lung metastases. Half of pts had Gleason >7. Treatment: 271 cycles (median: 3; range: 1-12); 1002 weekly infusions (median 11; range 1-48). Median dose intensity was 93%. Eighteen of 55 pts (32.7%) achieve ≥50% PSA response and 5 (9.1%) ≥80% PSA response. Radiological response was evaluable in 56 pts. PR was observed in 4 pt (7.1%) and SD in 29 pts (51.8%). Median PFS was 3.9 months. Median OS was 14.2 months. Most frequent toxicities of all grades as % of pts were: anemia (71.2%), asthenia (43.9%), thrombocytopenia (15.1%), leukopenia (24.2%), diarrhea (27.3%), nauseas (18.2%), neutropenia (12.1%), peripheral neuropathy (7.6%), and anorexia (18.2%). Grade 3-4: thrombocytopenia (4.5%), anemia (6%), neutropenia (3.0%), asthenia (10.6%), diarrhea (1.5%), anorexia (1.5%), No grade IV diarrhea nor febrile neutropenia were observed. Conclusions: Weekly cabazitaxel (10 mg/m2) plus prednisone administered to unfit pts seems a highly effective treatment and safe, with no grade 4 neutropenia, diarrhea or febrile neutropenia reported. Clinical trial information: NCT01518283