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Abiraterone acetate is a novel irreversible inhibitor of CYP17 that was recently approved for men with post-chemotherapy or chemo-naive castration-resistant prostate cancer. Unfortunately, this agent is not curative, and patients often ultimately develop resistance. However, men who progress after treatment with this new hormonal agent may be considered for another line of chemotherapy-based treatment. In 2004, docetaxel (D) and prednisone were found to improve survival compared with older regimens. More recently, cabazitaxel (C), a novel taxane chemotherapy, has been found to prolong survival in patients who exhibit disease progression during or after D chemotherapy. Here, we review the first clinical studies in which castration-resistant prostate cancer patients received chemotherapy with D or C after progression during abiraterone acetate treatment.

Purpose: The aim of this study was to evaluate the activity and safety of epirubicin (EPI), oxaliplatin (l-OHP) and 5fluorouracil (5FU) (EOF) followed by docetaxel (D), l-OHP and 5FU (DOF) in patients with advanced gastric or gastroesophageal junction (GEJ) cancer., Methods: Forty-five patients were enrolled: 26 gastric and 19 GEJ cancer. Median age was 69 years (range 34-83); ECOG performance status was 0-1 in 37 patients. Treatment consisted of EPI 50 mg/m(2) combined with l-OHP 130 mg/m(2) on day 1 and continuous infusion 5FU 750 mg/m(2) days 1-5 (EOF), every 3 weeks for a maximum of 4 cycles. After EOF completion, patients received D 70 mg/m(2) combined with l-OHP 130 mg/m(2) on day 1 and continuous infusion 5FU 750 mg/m(2) days 1-5 (DOF), every 3 weeks for a maximum of 4 cycles., Results: After sequential EOF/DOF, the overall response rate was 51.1 % (95 % CI 35.7-66.2 %) and 93.3 % of patients were progression free 6 months after the onset of chemotherapy. The median progression-free survival was 9.5 months (95 % CI 8.0-11.9 months), and the median overall survival was 15.8 months (95 % CI 13.6-18.9 months). Grade 3 neutropenia was observed in 15 patients (33.3 %) after sequential EOF/DOF., Conclusions: The sequential treatment EOF/DOF is feasible in well-selected patients with advanced gastric or GEJ cancer and shows encouraging survival results.

Background: Single-agent gemcitabine (GEM) has been considered for many years as the standard first-line treatment for advanced pancreatic cancer. However, recently, several studies reported encouraging activity and good tolerability for some combination regimens. Considering the apparently non-overlapping toxicity and the proved individual efficacy of GEM, oxaliplatin (L-OHP), and capecitabine (CAP), this randomized phase II study compared the activity and safety of the combination GEM, L-OHP, and CAP (GEMOXEL) versus GEM alone, in patients with metastatic pancreatic cancer., Materials and Methods: The treatment in GEMOXEL arm consisted of GEM 1,000 mg/m(2) as a 30-min intravenous infusion on days 1, 8, 15, 22, L-OHP 100 mg/m(2) i.v. on day 2, and CAP 1,500 mg/m(2)/day in two divided doses on days 1-14, every 21 days (one cycle). In both treatment groups, GEM was administered weekly for seven consecutive weeks followed by 1-week rest for the first 8 weeks, and thereafter, GEM was continued on days 1, 8, 15, every 28 days. Chemotherapy was administered until disease progression or unacceptable toxicity., Results: Sixty-seven patients were enrolled in the study. Thirty-four were randomly assigned to GEMOXEL and 33 to GEM. At 4 months, disease control rate was 79.4% with GEMOXEL versus 45.4 % with GEM (p = 0.004). The median progression-free survival was 6.8 months (95% CI 5.3-7.3 months) in GEMOXEL arm and 3.7 months (95% CI 2.9-4.7 months) in GEM arm (p < 0.001). The median OS was 11.9 months (95% CI 10.6-12.9 months) in GEMOXEL arm and 7.1 months (95% CI 5.5-9.1 months) in GEM arm (p < 0.001). Hematologic and non-hematologic toxicity was more severe with combination chemotherapy, yet still tolerable. No grade 4 adverse events were observed with either regimen., Conclusion: GEMOXEL regimen seemed to be safe and more efficient than the standard therapy with GEM alone in the treatment of metastatic pancreatic cancer.

Purpose: The dose limiting toxicity of oxaliplatin (l-HOP) is neurotoxicity, which is characterized by an acute neuropathy and a clinically distinct chronic neuropathy. This randomized study evaluated if prolonged l-HOP infusion over the conventional l-HOP schedule was useful in reducing acute and possibly chronic l-HOP induced neurotoxicity in colon and gastric cancer patients receiving l-HOP-based regimen as adjuvant chemotherapy., Methods: Sixty-four patients were randomly assigned to group A (26 colon and 6 gastric cancer) and to group B (23 colon and 9 gastric cancer). Chemotherapy in both groups consisted of l-HOP 85 mg/m(2) i.v. only on day 1, with leucovorin 100 mg/m(2) i.v. as a 2-h infusion followed by bolus 5-fluorouracil (5-FU) 400 mg/m(2)/day and a 22-h infusion of 5-FU 600 mg/m(2)/day, repeated for two consecutive days every 2 weeks for a maximum of 12 cycles. Patients in group A received l-HOP as a continuous 6-h i.v. infusion, and patients in group B received l-HOP as the conventional 2-h i.v. infusion., Results: The percentage of patients presenting with grade >/=2 neurotoxicity was statistically lower in group A than in group B (28.1% vs. 59.3%: P = 0.02). There was a statistically lower percentage of cycles with grade >/=2 neurotoxicity in group A (6.1%) than in group B (18.5%) (P < 0.001)., Conclusions: This study suggests that l-HOP as a continuous 6-h infusion is useful in preventing and reducing acute l-HOP induced neurotoxicity in patients with colon and gastric cancer receiving FOLFOX-4 regimen as adjuvant treatment.

Purpose: To assess the activity and safety of combined folinic acid (FA), 5-fluorouracil (5-FU) and mitomycin C (MMC) in metastatic breast cancer patients previously treated with at least two chemotherapy regimens., Patients and Methods: A total of 104 consecutive patients were enrolled for treatment with FA 100 mg/m(2) plus 5-FU 400 mg/m(2) i.v. on days 1-5, and MMC 3 mg/m(2) on days 3-5 (FFM). The cycles were repeated every 21 days until progression, severe toxicity or patient refusal., Results: Of the 104 patients, 96 were evaluable for response and toxicity. The overall response rate was 43% (95% confidence interval 32.8-53.2%); 40 patients achieved stable disease (42%) and 15 progressed (15%). In a retrospectively defined subgroup of patients with clinical resistance to taxanes (12 patients) or anthracyclines (14 patients), the response rate was 42%. The median time to progression was 8 months (3-18 months), and the median overall survival was 10.5+ months (2-36 months). The most common treatment-related adverse events were stomatitis, neutropenia, nausea/vomiting and diarrhea. Stomatitis, neutropenia and thrombocytopenia were the only grade 4 treatment-related adverse events, and occurred in no more than 3% of patients., Conclusion: The tested FFM regimen seems to offer a valid option for patients with metastatic breast cancer who have been pretreated with two or more chemotherapeutic lines or who have failed on regimens containing anthracyclines or taxanes.