Efficacy and Safety of Monthly Minodronate Therapy in Postmenopausal Breast Cancer Patients Receiving Aromatase Inhibitors.

BACKGROUND/AIM: Post-menopausal breast cancer (BC) patients who receive adjuvant aromatase inhibitor (AI) therapy may be at increased risk of bone loss, osteoporosis, and bone fracture. We aimed to evaluate the efficacy and safety of oral bisphosphonate minodronate in preventing bone loss complications. PATIENTS AND METHODS: Patients receiving AI and 80% of those with suboptimal bone mineral density (BMD) were prescribed monthly oral minodronate 50 mg every 4 weeks for 72 weeks. BMD, bone metabolism markers, incidence of bone fractures, medication compliance, and other adverse events (AE) were examined every 24 weeks following administration. RESULTS: Fifty postmenopausal BC patients with a median age of 64.0 years were enrolled. The mean value of lumbar spine BMD was higher than that of the value before the minodronate administration at each observation point. Before and after the treatment, the median serum values of Tartrate-resistant Acid Phosphatase 5b (TRACP-5b) (mU/dl) and serum type I collagen cross-linked N-telopeptide (NTX) (nmolBCE/l) were decreased from 535.7 and 18.5 to 230.1 and 11.9, respectively. No adverse grade 2 or higher event was observed throughout this study. CONCLUSION: The combined administration of minodronate and AIs was safe and effective in preventing bone loss complications in postmenopausal BC patients.

Preclinical and clinical studies of novel breast cancer drugs targeting molecules involved in protein kinase C signaling, the putative metastasis-suppressor gene Cap43 and the Y-box binding protein-1.

Breast cancer is a common cause of tumors in women. The development of effective adjuvant therapies using drugs such as anthracyclines, taxanes, and aromatase inhibitors has improved the survival of breast cancer patients. Molecular cancer therapeutics are also attracting attention, and targeted molecular therapies, such as trastuzumab, have already contributed to effective new treatments for breast cancer. Other candidate targeted molecular therapies for breast cancer, including erlotinib, gefitinib, lapatinib, bevacizumab, and celecoxib, are currently undergoing clinical evaluation, and promising results are expected. The current review provides an up-to-date summary of the preclinical and clinical development of these drugs for breast cancer. In particular, we focus on therapies targeting protein kinase C (PKC) signaling, the putative metastasis-suppressor gene Cap43/N-myc downstream-regulated gene 1 (NDRG1)/differentiation-related gene-1 (Drg-1), and the Y-box binding protein-1 (YB-1). The PKC signaling pathway is widely considered to be a promising target for the development of novel therapeutics. Cap43 expression is significantly modulated by estrogen and/or anti-estrogens in breast cancer cells that are positive for estrogen receptor-alpha (ER-alpha). Cap43 is therefore of particular interest as a molecular indicator of the therapeutic efficacy of anti-estrogenic agents in breast cancer. The nuclear expression of YB-1 plays an essential role in the acquisition of malignant characteristics by breast cancer cells, through epidermal growth factor receptor 2 (HER2)-Akt-dependent pathways. Basic research investigating the key selective molecular changes that sustain breast cancer growth and progression, as demonstrated for PKC, Cap43, and YB-1, is allowing the development of specific targeted molecular diagnostics and therapeutics.

Advanced chemoresistant breast cancer responding to multidisciplinary treatment with hyperthermia, radiotherapy, and intraarterial infusion.

We employed multidisciplinary therapy, consisting of hyperthermia, radiotherapy, and intraarterial infusion, for a patient with progressive advanced breast cancer that was resistant to epirubicin hydrochloride and cyclophosphamide (EC) therapy as well as being resistant to docetaxel hydrate, and obtained a good therapeutic response. Because estrogen and progesterone receptors were both negative and HER2 was 3(+), administration of trastuzumab was started, and this patient has shown no signs of recurrence at 33 months after our treatment. The results suggested that our multidisciplinary therapy can be an effective method for the treatment of progressive breast cancer showing resistance to major chemotherapy agents such as anthracyclines and taxanes.

[Intra-arterial cellular immunochemotherapy for unresectable pancreatic cancer with liver metastasis].

PURPOSE: To date, no treatment has had a significant impact on pancreatic cancer with liver metastasis. We performed locoregional cellular immunochemotherapy for unresectable pancreatic cancer with liver metastasis. SUBJECTS AND METHODS: A 71-year-old man was diagnosed for unresectable stage IVb pancreatic cancer. This patient was given intra-arterial infusion of gemcitabine (GEM) 400 mg/body and intravenous infusion GEM 600 mg/body, simultaneously. The day after GEM infusion, he was given intra-arterial autologous tumor cell activated T lymphocytes (AuTL). RESULTS: Tumor markers, such as CEA and CA19-9, had decreased a little. Primary tumor and metastatic liver tumor were reduced, but he died due to intra-abdominal dissemination within 5 months after diagnosis of unresectable pancreatic cancer. CONCLUSIONS: Reduced primary pancreatic tumor and metastatic liver tumor was obtained by locoregional cellular immunochemotherapy. But we could not control intra-abdominal dissemination. In conclusion, we suggest that intra-abdominal AuLT infusion in combination with intra-arterial AuLT infusion may be advisable to patients for unresectable pancreatic carcinoma with intra-abdominal dissemination.

Adjuvant chemotherapy after radical resection of squamous cell carcinoma in the thoracic esophagus: who benefits? A retrospective study.

BACKGROUND: A definitive combined modality therapy superior to surgery alone has not yet been found for esophageal cancer. This retrospective study investigated the impact of postoperative adjuvant chemotherapy in patients who underwent curative (R0) esophagectomy with radical lymphadenectomy. STUDY DESIGN: Two hundred and eleven patients with a squamous cell carcinoma in the thoracic esophagus who underwent transthoracic curative (R0) esophagectomy with radical lymphadenectomy, such as 3-field lymphadenectomy or total 2-field lymphadenectomy, between 1988 and 2000, were retrospectively reviewed. Ninety-four patients received postoperative chemotherapy - 2 courses of cisplatin (CDDP) plus fluorouracil (5-FU) or vindesine (VDS) - while the other 117 patients received surgery alone. The overall survival rate was compared between the two groups after being stratified by the numbers of the metastasis- positive lymph nodes. RESULTS: Only in the subgroup of patients with 8 or more lymph nodes metastasis- positive, the surgery-with-postoperative-chemotherapy group had a significantly better survival than the surgery-alone group. No significant difference was found in survival between the two groups in any other stratified subgroup. CONCLUSIONS: Postoperative adjuvant chemotherapy following curative (R0) esophagectomy with radical lymphadenectomy such as 3-field lymphadenectomy or total 2-field lymphadenectomy provided a benefit only in patients having metastasis in a large number - 8 or more - lymph nodes.