Although the same treatment strategy as used for small cell lung cancer, including second-line chemotherapy, is generally applied to metastatic neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma (MANEC) of the gastrointestinal tract (GIT; GIT-NEC/MANEC), the efficacy of amrubicin (AMR) for GIT-NEC/MANEC is not well known. We retrospectively analyzed platinum-refractory GIT-NEC/MANEC patients who received AMR between February 2004 and July 2012 at the National Cancer Center Hospital. The AMR dose administered was 30-45 mg/m on days 1-3 every 3-4 weeks. The overall response rate according to Response Evaluation Criteria in Solid Tumors guidelines, version 1.0, progression-free survival, overall survival, and adverse events by National Cancer Institute-Common Terminology Criteria for Adverse Events guidelines, version 4.0 were evaluated. Nineteen patients received AMR. The response rate for 16 assessable patients was 18.8% (95% confidence interval, 4.1-45.7), the median progression-free survival was 3.8 months (2.3-5.3), and the median overall survival was 7.7 months (7.1-8.2). Grade 3/4 neutropenia occurred in 52.6% of patients and febrile neutropenia occurred in 10.5%. Other nonhematological toxicities were mild and treatment-related deaths were not observed. AMR may have a modest effect, with tolerable toxicities, on patients with platinum-refractory GIT-NEC/MANEC. Further prospective evaluations are warranted.

PolyADP-ribosylation is a post-translational modification of proteins, and poly(ADP-ribose) (PAR) polymerase (PARP) family proteins synthesize PAR using NAD as a substrate. Poly(ADP-ribose) glycohydrolase (PARG) functions as the main enzyme for the degradation of PAR. In this study, we investigated the effects of Parg deficiency on tumorigenesis and therapeutic efficacy of DNA damaging agents, using mouse ES cell-derived tumor models. To examine the effects of Parg deficiency on tumorigenesis, Parg+/+ and Parg−/− ES cells were subcutaneously injected into nude mice. The results showed that Parg deficiency delays early onset of tumorigenesis from ES cells. All the tumors were phenotypically similar to teratocarcinoma and microscopic findings indicated that differentiation spectrum was similar between the Parg genotypes. The augmented anti-tumor therapeutic effects of X-irradiation were observed under Parg deficiency. These results suggest that Parg deficiency suppresses early stages of tumorigenesis and that Parg inhibition, in combination with DNA damaging agents, may efficiently control tumor growth in particular types of germ cell tumors.

A 57-year-old woman was admitted with lower abdominal pain and bloody bowel discharge. She was diagnosed with rectal tumor by colonoscopy, and a biopsy was performed. Surgery was performed, resulting in a diagnosis of rectal paraganglioma. Since recurrence was confirmed three years later, reoperation was done, and chemotherapy with cyclophosphamide, vincristine and dacarbazine (CVD) was subsequently carried out for further recurrence. After the administration of up to 15 courses of CVD, we delivered best supportive care due to disease progression. She died a year and a half after starting chemotherapy. We herein report this rare disease with a review of the relevant literature.