Background: Penile cancer is rare and there are scant data on the optimal chemotherapy regimen. The majority of trials are single arm, non-randomized studies. Here we report on a systematic review aiming to compare taxane combination chemotherapy regimens with non-taxane regimens for APC. Methods: A systematic review was conducted in accordance with the PRISMA guidelines. Medline, Embase and Cochrane Central Register of Controlled Trials databases were searched using the following terms: penile cancer, penis, antineoplastic combined chemotherapy, taxane, docetaxel, paclitaxel, platinum, cisplatin, carboplatin. Studies were identified using preplanned eligibility criteria by 2 investigators (EA-E and JR). Data were extracted independently by EA-E and JR. Studies were weighted by study sample size and those comparing taxane-based chemotherapy were compared to non-taxane therapy using the Mann Whitney test. Results: The search identified 1929 publications and 40 were selected for further assessment. Of these, 8 met eligibility criteria (7 prospective and 1 retrospective). Three studies tested taxane combinations (docetaxel, cisplatin and 5FU [DCF] and paclitaxel, ifosfamide and cisplatin [TIP]). A total of 148 men with APC were treated with non-taxane regimens and 98 men received a taxane combination. Patient characteristics (age, ECOG status, stage, number of cycles) were comparable between the two groups. Partial response and overall response rates were significantly higher in the taxane versus the non-taxane group (35.7% vs. 24.2% p = 0.01 and 41.9% vs. 32.5% p = 0.007) respectively. Grade3/4 neutropenia was significantly higher in taxane group than non-taxane group (27.8% vs 19.4% p = 0.02). Median PFS and OS was numerically but not significantly higher in the taxane versus the non-taxane group (5.7 vs. 4.4 months, p = 0.45 and 12.1 vs 10 months, p = 0.48, respectively). Conclusions: Compared to non-taxane-based regimens, taxane combinations have higher response rates and may improve survival in APC. Hematologic toxicities are worse with taxane containing regimens. Taxane combinations should be the preferred regimen for suitable men with APC.