Disseminated carcinomatosis of the bone marrow with disseminated intravascular coagulation as the first symptom of recurrent rectal cancer successfully treated with chemotherapy: A case report and review of the literature.

Disseminated carcinomatosis of the bone marrow (DCBM) is a condition in which bone marrow (BM) metastases diffusely invade the BM, and is frequently accompanied by disseminated intravascular coagulation (DIC). While prostate, lung, breast and stomach malignancies, in addition to neuroblastoma, are the most prevalent non-hematological malignancies to metastasize frequently to the BM, colorectal cancer is a malignancy that rarely metastasizes to the BM. The present case describes a 65-year-old male patient treated by resection and one course adjuvant chemotherapy for stage IIIC rectal cancer who presented with nasal bleeding at 8 months post-surgery. A blood test exhibited DIC. A BM biopsy was performed and the definitive diagnosis was DCBM with DIC. Promptly, anti-DIC treatment and chemotherapy with a modified FOLFOX6 (folinic acid, leucovorin (LV), 5-fluorouracil (5-FU) and oxaplatin) regimen was started. Following 1 cycle of chemotherapy, DIC was improved and subsequent to 2 cycles of modified FOLFOX6 the patient was discharged. The patient was alive 263 days subsequent to the diagnosis of DIC, but succumbed to carcinomatous meningitis as a result of disease progression. To the best of our knowledge, this is the first report of DCBM with DIC of curatively resected rectal cancer as the first presentation of relapse that was successfully treated with aggressive therapy, including chemotherapy.

Phase I trial of 5-FU, docetaxel, and nedaplatin (UDON) combination therapy for recurrent or metastatic esophageal cancer.

PURPOSE: The aims of this dose-escalating phase I study were to determine the maximum tolerable dose (MTD) and recommended dose (RD) of 5-fluorouracil (5-FU), docetaxel, and nedaplatin (UDON) combination therapy for future phase II studies, and to evaluate the safety and efficacy of this regimen in patients with untreated recurrent or metastatic esophageal cancer. METHODS: Patients were administered 5-FU on days 1-5, docetaxel on days 1 and 15, and nedaplatin on day 1 at 4-week intervals. The dose levels of 5-FU/docetaxel/nedaplatin were escalated as follows (mg/m(2)): level 1, 800/30/80; level 2, 800/30/90; and level 3, 800/35/90. Toxicity was evaluated using Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Overall, nine patients were enrolled in this study. All patients had an Eastern Cooperative Oncology Group performance status of 0 or 1 and were diagnosed with squamous cell carcinoma. No dose-limiting toxicity was observed at any level, and planned dose escalation was completed without reaching the MTD. No grade 4 or higher toxicity was observed in this study. The observed grade 3 hematological toxicities included neutropenia in five patients (55.6 %) and leukopenia in three patients (33.3 %). None of the patients developed febrile neutropenia, and no grade 3 or 4 non-hematological toxicities were observed. The overall response rate was 77.8 %, including two complete responses, and the disease control rate was 100 %. CONCLUSION: The RD of UDON was identified as level 3. The good tolerability and high antitumor efficacy of this regimen warrant further evaluation in this setting.

Risk factors for cisplatin-induced nephrotoxicity and potential of magnesium supplementation for renal protection.

BACKGROUND: Nephrotoxicity remains a problem for patients who receive cisplatin chemotherapy. We retrospectively evaluated potential risk factors for cisplatin-induced nephrotoxicity as well as the potential impact of intravenous magnesium supplementation on such toxicity. PATIENTS AND METHODS: We reviewed clinical data for 401 patients who underwent chemotherapy including a high dose (≥60 mg/m2) of cisplatin in the first-line setting. Nephrotoxicity was defined as an increase in the serum creatinine concentration of at least grade 2 during the first course of cisplatin chemotherapy, as assessed on the basis of National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. The severity of nephrotoxicity was evaluated on the basis of the mean change in the serum creatinine level. Magnesium was administered intravenously to 67 patients (17%). RESULTS: Cisplatin-induced nephrotoxicity was observed in 127 patients (32%). Multivariable analysis revealed that an Eastern Cooperative Oncology Group performance status of 2 (risk ratio, 1.876; P = 0.004) and the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) (risk ratio, 1.357; P = 0.047) were significantly associated with an increased risk for cisplatin nephrotoxicity, whereas intravenous magnesium supplementation was associated with a significantly reduced risk for such toxicity (risk ratio, 0.175; P = 0.0004). The development of hypomagnesemia during cisplatin treatment was significantly associated with a greater increase in serum creatinine level (P = 0.0025). Magnesium supplementation therapy was also associated with a significantly reduced severity of renal toxicity (P = 0.012). CONCLUSIONS: A relatively poor performance status and the regular use of NSAIDs were significantly associated with cisplatin-induced nephrotoxicity, although the latter association was marginal. Our findings also suggest that the ability of magnesium supplementation to protect against the renal toxicity of cisplatin warrants further investigation in a prospective trial.

MPO-ANCA-positive anti-glomerular basement membrane antibody disease successfully treated by plasma exchange and immunosuppressive therapy.

Anti-glomerular basement membrane (GBM) antibody disease is clinically manifested as rapidly progressive glomerulonephritis (RPGN) with crescentic changes. The renal prognosis is poor. We report here the case of a 61-year-old woman with myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-positive anti-GBM antibody disease. This patient was referred to our hospital because of RPGN. Anti-GBM antibody was positive with a titer of 38 EU. The MPO-ANCA titer was 65 EU. Chest imaging examination revealed pulmonary multiple nodules. ANCA-associated vasculitis was suspected. Renal pathology revealed cellular crescents in 13 out of 17 glomeruli. Immunofluorescence with anti-IgG antibody, anti-C3 antibody, and anti-fibrin antibody showed linear staining along the glomerular capillary walls. Based on these findings, the patient was diagnosed with anti-GBM antibody disease. Hemodialysis was started because of uremic syndrome with elevated serum creatinine (6.84 mg/dL). In addition, treatment with plasma exchange using 3.6 L (90 mL/kg) of fresh frozen plasma combined with an oral dose of 40 mg of prednisolone was initiated. Within 3 weeks, both types of autoantibodies became undetectable. Subsequently, this patient achieved dialysis independence and remission of glomerulonephritis. No adverse effects were observed. In patients with MPO-ANCA-positive anti-GBM antibody disease, intensive therapy predominantly with plasma exchange might be operative, even though renal function is less likely to recover.