Immunotherapy with Immunomodulatory Agents Prolong Survival of Advanced Ovarian Cancer with Brain Metastatis

Abstract

The prognosis of patients with metastatic ovariancancer is poor. Treatment with surgery and chemotherapeutic drugs alone is rarely curative. In the past few years, the development of immunotherapy, targeted therapy, angiogenesis inhibitors, and tyrosine kinase inhibitors has provided better treatment choices for patients with metastatic ovarian cancer. A 62-year-old woman was diagnosed on October 2008, with advanced ovarian cancer, stage IIIc. She underwent maximal debulking surgery (including abdominal total hysterectomy, bilateral salpingo-oophorectomy, total omentectomy, excision of multiple peritoneal carcinomatosis, bilateral pelvic lymph node dissection, and end-to-end enteroanastomosis) with concurrent intraperitoneal treatment by hyperthermia lavage (5000 ml, 43 cesium degree) with immunomodulatory agent celecoxib (cyclooxygenase-2 inhibitor) to create host immunosurveillance for consolidation therapy. The standard pacitaxol-based chemotherapy totally 6 times were given monthly, combined with immunotherapy. The immunomodulatory agents used were picibail (OK-432), interferon-alpha, celecoxib (cyclooxygenase-2 inhibitor), and aldeleukin (IL-2). We checked her immune risk profiles (IRP) before and after therapy. We found that the operative stress rendered host immunosurveillance switch less immunogenicity [CD4/CD8 ratio less 1] to mimic immunocompromised status. She had relapse of ovarian cancer with brain metastasis about 28 months later (on Feb 2011). She received surgery, chemo-radiation therapy and immunotherapy (ICRT) for multiple brain metastasis. Later, she had relapse of new lesions over right cerebellum on August 2012 and she received concurrent immunochemoradiotherapy. After whole brain radiotherapy (3000 cGY/ per time) totally 10 times and “add on” standard dose avastin 15 mg/kg and single or combined chemotherapy and dose dense chemotherapy, the metastatic cerebellum tumor had complete remission. Unfortunately, she was found to have huge right frontal and temporal brain metastasis with extended to 4th ventricle on May 2015. She received manitol and dexan to control her increased intracranial pressure, and followed by avastin (bevacizumab) and immunochemotherapy. Immunomodulatory agents, including picibanil (OK-432), pamidronate, interferon-alpha, celecoxib (cyclooxygenase-2 inhibitor) and chemotherapies (paclitaxol 135 mg/m2- based chemotherapy per 3 weeks for 6 times) were given. Later, she underwent craniotomy to removal of suspect residual brain metastasis lesion and the pathology showed necrosis brain tissue. The patient achieved a dramatic remission of metastatic brain lesions after “obapac” (OK-432, bevacizumab [avastin], pamidronate, intereferonalpha, and celecoxib) and chemotherapies. Our case demonstrates the dramatic promise of immunomodulatory therapy to induce complete remission of a metastatic cancer nodule. This case suggests the potential value of immunotherapy to augment host immunosurveillance to improve survival of metastatic ovarian cancer.