The incidence of prostate cancer is increasing and the patients are generally of relatively advanced age. There has been an increase in the use of hormonal therapy in such cases. However, hormonal therapy for prostate cancer increases the risk of fracture. Bisphosphonates have been reported to prevent the bone loss caused by hormonal therapy. Therefore, oral bisphosphonates will play an important role in preventing bone loss in prostate cancer patients undergoing hormonal therapy.

Paclitaxel, one of the taxanes, has been used to treat malignant tumors such as breast cancer. It is known to cause cystic maculopathy as an unusual ocular side effect. Here, we describe the clinical features of a patient who suffered cystic maculopathy during paclitaxel therapy.

In May 2007, a 48-year-old woman was admitted to our hospital for acute intestinal obstruction, and she was subsequently diagnosed with metastatic colorectal cancer in the sigmoid colon. Jejunum-ileum anastomosis and colostomy were performed as palliative surgery because the locally-advanced primary tumor had involved the ileum and other surrounding organs and formed huge mass. After placement of a central venous port, palliative chemotherapy mFOLFOX6 was commenced. In May 2008, mFOLFOX6 was replaced with FOLFIRI because of progression of both the metastasized and the primary tumors. On November 20, 2008, cetuximab was added to FOLFIRI because of the further disease progression. However, on December 24, 2008, the patient presented with sudden-onset dyspnea. Her blood gas analysis revealed severe hypoxemia and metabolic acidosis, and CT scan showed bilateral pulmonary artery embolism. After intensive treatment, the patient was able to walk under the room-air condition. However, on January 19, 2009, she died of pneumonitis. We believe that this is an interesting case with respect to the relationship between pulmonary embolism and malignancy and may hint at a causal relationship between pulmonary embolism and cetuximab, which is currently uncertain. We report this case herein along with a literature review.

The patient was a 70-year-old woman, who had undergone total gastrectomy and splenectomy with D2 lymph node dissection, for stage II gastric cancer. We admitted S-1 of 80 mg/day in adjuvant chemotherapy on postoperative day 28. There were no adverse events for one week, and she was discharged. Severe diarrhea occurred 6 days following discharge, but she continued to take S-1. Two weeks after discharge, she visited our hospital, suffering from severe dehydration (grade 4), leucopenia (grade 4)and thrombocytopenia (grade 3). Unfortunately, she died of lung edema and multiple organ failure 28 days after chemotherapy. We measured the mRNA expression level of dihydropyrimidine dehydrogenase (DPD) of the patient's liver by the Dannenberg Tumor Profile method. The expression level of DPD was significantly low, so we suggested that the severe bone marrow suppression might have been caused by the disordered metabolism of 5-FU.

Paclitaxel (PTX) is one of the most important breast cancer treatment drugs. However, severe hypersensitivity reactions such as decreases in blood pressure and impaired breathing occur with high frequency. For the prevention of such hypersensitivity reactions, administration of a premedication composed of three components, diphenhydramine, ranitidine (or famotidine), and dexamethasone, has been advised in package insert information of medicine. Administration of diphenhydramine is difficult in breast cancer patients complicated with closed-angle glaucoma, because diphenhydramine has a weak anticholinergic adverse effect which can induce mydriasis and glaucoma attack. We studied the prevention of severe hypersensitivity reactions and of glaucoma attack in 2 breast cancer patients complicated with closed angle glaucoma at our hospital from April 2007 to March 2008. We switched from diphenhydramine to fexofenadine as the medicine to prevent hypersensitivity reactions. Hypersensitivity reactions were not observed throughout all courses in both patients, and no glaucoma attack was observed.

Rituximab, a chimeric monoclonal antibody against the CD20 protein, has an antineoplastic effect resulting from antibody dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). In patients with rituximab-combined chemotherapy, a decline in immunoglobulin can be observed. This is more likely to cause virus reactivation, such as Herpes (H) zoster. However, this fact has not reported in a large-scale study. In order to research immunodeficiency conditions in patients with rituximab-combined therapy, we examined the alteration in immunoglobulin level throughout the treatment among 205 cases with B-cell lymphoma. We also studied the prevalence of H. zoster in those cases. The IgG level throughout the treatment was measured in 89 patients in the research. The median post-chemotherapy IgG level was 41.1% lower than its pre-chemotherapy IgG level. In 58 cases, the IgG level following chemotherapy was below the normal level. In 22 cases, the IgG level dropped to less than half of the pre-chemotherapy level. H. zoster developed in 17 cases (8.3%). There was no significant difference in IgG level between H. zoster-onset cases and non-H. zoster-onset cases. Antibody-mediated immunity can decrease greatly and prolong in cases with rituximab in combination with chemotherapy. Therefore, infection control is considered to be important.

Recently, Bevacizumab became one of the major therapeutics in the care of advanced and recurrent colorectal cancer patients in Japan. The present study evaluated the efficacy and the adverse events in 23 patients who were treated with Bevacizumab.

A 59-year-old woman began to complain of cough, dyspnea, and fever 2 weeks after 3 courses of chemotherapy with cyclophosphamide (800 mg) and adriamycin (80 mg) for breast cancer. Chest radiography showed diffuse ground-glass shadows in the central areas of bilateral lung fields. Chest CT also showed diffuse ground-glass opacities in the central areas of bilateral lung fields. Arterial blood gas analysis revealed mild hypoxia. A lymphocyte stimulation test with peripheral blood lymphocytes for cyclophosphamide was negative. A mild increase of lymphocytes was observed in the cell population of bronchoalveolar lavage fluids and no microorganisms were detected. Her respiratory condition improved after glucocorticoid therapy. A rechallenge test with cyclophosphamide was performed after obtaining informed consent. There was no significant change in symptoms or chest radiography results 24 hours after intravenous administration of cyclophosphamide (100 mg). However, a transient decrease of PaO2 with peripheral eosinophilia was observed. Thus, a diagnosis of early-onset cyclophosphamide-induced pneumonitis was established.

The study aimed to assess our newly devised CDDP delivery system designed to provide targeting potential and a sustained release of the anticancer agent. Seventy percent deacetylated chitin was applied as a drug carrier. We prepared two different types of systems with two different procedures: namely, system A with direct method and system B with indirect method. The targeting property of the system was evaluated ex vivo with measuring adhesive force between each system and human colonic mucosa. The release behavior of the CDDP from the system was examined in vitro. The anticancer activities of the released CDDP were also examined in vitro using human gastric cancer cell line, MKN-45. Each system was a viscose elastic solution. The adhesive forces of the novel systems were stronger at 37 degrees C than that of 25 degrees C. Each system provided a sustained release of CDDP. The released CDDP demonstrated effective growth suppression activity against the MKN-45 cancer cells. The novel systems basically showed a favorable targeting function and a sustained release of CDDP, which effectively provided a growth inhibition potential against human cancer cell line. Our newly devised CDDP delivery systems are promising as a novel approach to cancer chemotherapy.

To compare mRNA levels in cancer cells and protein levels in cancerous tissue in order to evaluate the expression of dihydropyrimidine dehydrogenase (DPD).

The operation for liver metastases from colorectal cancer is increasing due to a progress of chemotherapy. On the other hand, the live damage induced by chemotherapy affects on post operative course. We studied histopathological liver injury on the patients who received preoperative chemotherapy. Between January 2004 and May 2009, forty seven patients underwent hepatectomy for colorectal liver metastases after systemic chemotherapy, and the remnant liver was histopathologically investigated about sinusoidal dilatation and non-alcoholic steatohepatitis. As a result, chemotherapy including irinotecan or oxaliplatin was significantly associated with sinusoidal dilatation, and female gender or higher body mass index was correlated with non-alcoholic steatohepatitis. These results should be taken into consideration before liver resection in patients who have received preoperative chemotherapy.

A 67-year-old woman with acute Philadelphia-chromosome-positive mixed phenotype leukemia developed bilateral periorbital ecthyma gangrenousum (EG) subsequent to periorbital edema while undergoing combined imatinib mesylate (imatinib) chemotherapy. Although initial periorbital edema was considered an imatinib side effect, the lesion deteriorated rapidly with high fever in the neutropenic phase, and the woman died of septic shock. Cultures from blood and exudative fluid grew Pseudomonas aeruginosa, after which EG was diagnosed. EG is a well-recognized emergent cutaneous infection most commonly associated with Pseudomonas aeruginosa bactremia. Because some patients present with EG a few days prior to developing life-threatening septicemia, it is important that EG be diagnosed correctly. Imatinib side effects such as edema are usually tolerable, and imatinib is widely used to treat Philadelphia-chromosome-positive leukemia, particularly in those with acute lymphoblastic leukemia, and neutropenic patients undergoing imatinib therapy are expected to increase in number. Delay in initiating appropriate therapy is correlated with poor outcome, so drug side effects and EG must be carefully differentiated when skin edema with surrounding erythema is noted in neutropenic patients undergoing imatinib therapy.

A modified diet in renal disease (MDRD), a formula to estimate glomerular filtration rate (GFR), was proposed by Levey in 2006. In this study, we compared the dosage of carboplatin (CBDCA) calculated using MDRD with that calculated by conservative creatinine clearance (Ccr), and investigated the actual dosage given and the incidence of its adverse effects. In the 101 patients undergoing chemotherapy including CBDCA, the dosage calculated from the estimated GFR was 16% lower than that based on the estimated Ccr. This difference was greater in those under 65 years, women and those with a body mass index (BMI) > or =25. The most prominent incidence of adverse effects was thrombocytopenia in patients with lung cancer. In men, a serum creatinine level of > or =0. 6 mg/dL, GFR of <50 mL/min/1. 73 m(2) and a combined use of gemcitabine were cited as the factors responsible for the development of thrombocytopenia. It was concluded that the MDRD formula is an effective tool for evaluating patients with impaired renal function. It was suggested, on the other hand, that the dosage for medication should be decided by giving due consideration to factors other than renal functions.

A 79-year-old woman with colon cancer and multiple liver metastases was admitted to our hospital for systemic chemotherapy. She underwent first cycle of modified FOLFOX6 chemotherapy. She was confused on treatment day 5. Blood test revealed her serum ammonia level to be 121 microg/dl. We diagnosed 5-fluorouracil (5FU)-induced hyperammonemia. Conservative treatment resulted in improvement of metal status. The reason for hyperammonemia after administration of 5FU was the excess production of ammonium from metabolites of 5FU.

This study was aimed to propose a novel dosing schedule of docetaxel based on alpha(1)-acid glycoprotein (AGP)as an index. For this purpose, we performed Monte Carlo simulation using a population pharmacokinetic/pharmacodynamic (PPK/PPD) model, which we previously developed to estimate the ANC Nadir distribution after docetaxel administration. AGP values, which were incorporated in PPK/PPD, were sampled from normal distributions (S.D. 44, range from 19 to 259), as various mean levels of 125, 150, 175 and 200 (mg/dl). Monte Carlo simulation was conducted using docetaxel doses of 40, 50 and 60 (mg/m(2)) for each AGP distribution. Simulation was performed 200 times, and distributions of ANC Nadir median were obtained from simulations. We accepted a dose when 20 percentile of the distribution of ANC Nadir median was greater than 500 (counts/microl), in order to avoid the grade 4 neutropenia. From the results of simulations, 40, 50, 60 and 60 doses (mg/m(2)) were recommended for 125, 150, 175, and 200 AGP mean (mg/dl) respectively. Secondly, to evaluate this dosing schedule, we adopted these recommended doses to 16 patients whose ANC Nadir observed is lesser than 500, and simulated the ANC Nadir. The number of patients whose simulated time below ANC=500 was higher than 6 days decreased from 8 to 2, implying that this dosing schedule might be effective to avoid neutropenia induced by docetaxel. In conclusion, we proposed a novel dosing schedule of docetaxel using AGP as an index, which might be effective to avoid neutropenia induced by docetaxel.

Taste disorders are a common complaint among cancer patients undergoing chemotherapy on an ambulatory basis. We conducted a survey on the incidence of such disorders among 74 patients, and 45.95% (34 of 74 patients) developed taste disorders. When stratified by medication into a regimen including 5-FU and one including taxanes, taste disorders were found in 59.0% (23 of 39 patients) of the former and 60.0% (9 of 15) of the latter. The survey also included the effects of taste disorders on patients appetites. Both regimens led to reduced appetite in a number of these patients (39.1% and 44.4%, respectively). Among patients on the 5-FU-containing regimen, the FOLFOX/FOLFIRI therapy was found to be responsible for loss of appetite. Regarding change in tastes, many patients stated that the medication dulled their taste sensation except for bitterness; their capacity to sense intensity of taste remained unchanged. It was found that acute taste disorders develop frequently among patients on a high dosage of 5-FU or a taxane-containing regimen.

A paclitaxel injection NK (NK) is a generic product containing the same amount of ingredients as a Taxol Injection. We examined the safety of NK in clinical practice compared to the original drug. Our results suggested that the safety of NK and the original drug are similar in adjuvant therapy for breast cancer.

We examined the association between chemotherapy-induced myelosuppression and prognosis in extensive-stage small cell lung cancer (ED SCLC). We retrospectively analysed 91 patients with ED SCLC who received a combination of cisplatin or carboplatin, etoposide or irinotecan between November 1995 and December 2007. Patients were categorized into two groups (grade 0 to 2 or grade 3 to 4) according to the worst neutropenia, thrombocytopenia, or anemia during first-line chemotherapy and were analysed for overall survival (OS) and time to progression (TTP). By univariate analysis, OS and TTP were significantly better in patients who developed grade 3 to 4 neutropenia than those who developed grade 0 to 2. Additionally, performance status (PS), LDH (lactate dehydrogenase), and neuron-specific enolase were prognostic factors for OS. By multivariate analysis, PS was an independent prognostic factor for OS. There were no independent prognostic factors for TTP. Myelosuppression during chemotherapy is not a prognostic factor in ED SCLC.

We performed combination chemotherapy using S-1 and CPT-11 for advanced and recurrent stomach carcinoma in order to study the clinical efficacy thereof. The subjects comprised 13 patients aged 55 to 78 with a PS of 0 to 2, who had histologically confirmed unresectable stomach carcinoma or who had undergone a non curative resection with postoperative recurrence, all having measurable or assessable lesions with no severe damage in the principal organ, and from whom informed consent in writing had been obtained. 80 to 120 mg/day of S-1 were orally administered daily for 21 days according to the body surface area. 60 mg/m2 of CPT-11 was administered on Days 1 and 15. After the administration of S-1 for 3 weeks, from 1- to 2-week-long drug holidays were provided, thereby establishing a total of 4 to 5 weeks as 1 course. This was repeated as many times as possible. Thirteen subjects were registered during the period from November 2001 to February 2004. The details thereof are as follows: 9 male subjects and 4 female subjects with a median age of 65 years, wherein 1 subject had a PS of 0, 3 subjects had a PS of 1, and 9 subjects had a PS of 2. The results for all of the subjects showed that 5 subjects had PR, and the response rate was 38%. Grade 3 or higher adverse events consisted of leucopenia in 38.5%, neutropenia in 46.2%, anemia in 15.4%, and diarrhea in 7.7%. The median survival time (MST) for all of the subjects was 259 days. Specifically, the MST was 248 days for the subjects with a PS of 2 for whom 2 drugs were concomitantly used, and it was equal or longer for the subjects with a PS of 2 who were treated under the sole regimen of S-1. A review of this study showed that side effects were more frequently observed in the subjects with a PS of 2 than in those with a PS of 0 to 1. Furthermore, the average number of courses that were administered to the subjects with a PS of 0 to 1 was 8.5, against 3.6 courses on average in subjects with a PS of 2, thus showing a significant difference between the 2 groups. According to the above results, it is believed that there is a difference in the tolerability of the anticancer drugs between subjects with a PS of 0 to 1 and those with a PS of 2. It is also considered necessary to adjust the dosage of the anticancer drugs and the dosing period for patients with a PS of 2 when preparing a chemotherapeutic regimen for digestive carcinoma, including stomach carcinoma. The present regimen will be further studied to evaluate its potential use after second-line therapy for advanced and recurrent stomach carcinoma.