Administration of zoledronic acid enhances the effects of docetaxel on growth of prostate cancer in the bone environment

BACKGROUND: After development of hormone-refractory metastatic disease, prostate cancer is incurable. The recent history of chemotherapy has shown that with difficult disease targets, combinatorial therapy frequently offers the best chance of a cure. In this study we have examined the effects of a combination of zoledronic acid (ZOL), a new-generation bisphosphonate, and docetaxel on LuCaP 23.1, a prostate cancer xenograft that stimulates the osteoblastic reaction when grown in the bone environment. METHODS: Intra-tibial injections of LuCaP 23.1 cells were used to generate tumors in the bone environment, and animals were treated with ZOL, docetaxel, or a combination of these. Effects on bone and tumor were evaluated by measurements of bone mineral density and histomorphometrical analysis. RESULTS: ZOL decreased proliferation of LuCaP 23.1 in the bone environment, while docetaxel at a dose that effectively inhibited growth of subcutaneous tumors did not show any effects in the bone environment. The combination of the drugs significantly inhibited the growth of LuCaP 23.1 tumors in the bone. CONCLUSION: In conclusion, the use of the osteolysis-inhibitory agent ZOL in combination with docetaxel inhibits growth of prostate tumors in bone and represents a potential treatment option

Gynecologic oncology group trials of chemotherapy for metastatic and recurrent cervical cancer

Because only 16% of patients with metastatic cervical cancer are alive 5 years after diagnosis, the Gynecologic Oncology Group (GOG) has carefully designed and conducted many phase II studies to identify promising drugs. Cisplatin has emerged as the most active single agent with overall response rates of 19%. Recent phase III trials have documented response rates of 27% and 39% when cisplatin has been combined with either paclitaxel or topotecan, respectively. The comparison of cisplatin to cisplatin plus topotecan in GOG-179 has yielded the first study to show a statistically significant impact on the overall response rate, median progression-free survival, and median survival, with all outcome measures favoring the two-drug regimen. Despite these encouraging results, however, most of the responses are partial and of short duration. The need for novel combinations and the implementation of active biologic agents is implicit. The accumulated data in this disease setting, as evidenced by the experience of the GOG, are presented in this review

Pharmacologic Management of Advanced Cervical Cancer: Antiangiogenesis Therapy and Immunotherapeutic Considerations

As a consequence of disparities in access to and utilization of preventative healthcare, the incidence and death rates from cervical cancer remain substantial in the face of indisputable evidence that screening saves lives. While disparities persist, there will be an urgent need for research into the treatment of advanced forms of this disease. In this review, we explore the evolution of the treatment of metastatic, recurrent, and persistent cervical cancer from cytotoxic agents to targeted therapy. We discuss why targeted therapies are unlikely to produce sustained responses alone but may be more successful in combination with immunotherapies. We also provide a rationale for the potential next phase in treatment of this challenging disease—combined therapy with antiangiogenic agents and immune checkpoint inhibitors. In doing so, we highlight recent paradigm shifts within cancer therapeutics, including the shift in focus from the tumor cell itself to the tumor microenvironment, and from stimulating the immune system to inhibiting the inhibitors of an adequate immune response