OBJECTIVES: Standard first-line treatment for patients with mHRPC is Docetaxel(D)-based chemotherapy. Published results from randomised clinical trials of second-line treatments after D failed to provide definitive conclusions about clinical efficacy largely due to paucity of data. This study sought to identify non-randomised trials of second-line chemotherapy in mHRPC patients pre-treated with D and present related survival and clinical benefits. METHODS: Pubmed and Embase were used to perform a systematic literature review (SLR) (2000 – 2010). Both comparative and non-comparative non-randomised evidence were extracted from prospective and retrospective studies. Targeted population was patients with mHRPC failing previous D-based regimens. Endpoints included Overall-Survival (OS), Progression-Free-Survival (PFS) and PSA-response rate. RESULTS: Among the 825 records screened, 30 studies met the inclusion criteria, 2 of which were comparative. Of these, 10 addressed rechallenge with D and 7 addressed mitoxantrone (MTX); the remaining 18 studies considered various other regimens. Treatment was with either single-agent or combination regimens. Ninety-three percent of studies included <50 patients. PFS and PSA response definitions varied between trials. For studies evaluating rechallenge with D, the median OS and PFS varied from 41-76 weeks and from 15-39 weeks respectively. For MTX, the median OS and PFS varied from 39-48 weeks and 13-16 weeks respectively. For other chemotherapy regimens, the median OS and PFS varied from 51-104 weeks and 9-17 weeks respectively. PSA response rates varied from 24-70% to D rechallenge, from 4-33% to MTX based regimens and from 0-60% to other regimens. CONCLUSIONS: The SLR showed a lack of available non-randomised evidence and among the selected studies evidence was not strong enough due to small sample sizes, non-comparative nature and variable PFS and PSA response definitions. This literature review demonstrates that it is difficult to infer the clinical efficacy of mHRPC 2nd line chemotherapy.