With the introduction of rituximab to chemotherapy in lymphoma, CHOP changed to R-CHOP in elderly, intermediate risk DLBCL (diffuse large B-cell lymphoma) patients. Although the treatment is not yet standard, due to insufficient evidence, in clinical practice it is an R-containing regimen, for example, in mantle cell lymphoma, such as HyperCVAD/MA to R-HyperCVAD/MA. Recently, another group and ours reported the presence of rituximab resistance during R-containing chemotherapy. If the lymphoma is bulky,the overexpression of CD 55 (complement regulatory molecule) leads to resistance to rituximab. When the patients evidenced the loss of CD 20 antigen in refractory/relapsed lymphoma after R-containing therapy, some patients showed the presence of CD 20 point mutation. In the cases of refractory/relapsed cases, radioimmunotherapy or other monoclonal antibodies are prepared, including Zevalin and CD 22, CD 40, CD 74, and HLA-DR targeting antibodies. Not only monoclonal antibodies but also HDACI or bortezomib (NF-kappaB) and other signal inhibitors (for Akt, ERK/MAPK) have been developed. In Japan, we must consider the higher speed of infusion rituximab and we must prepare standard therapy for lymphoma because of recruiting phase I/II clinical trials after use of rituximab for easy entry.

Trastuzumab is a recombinant humanized monoclonal antibody directed against HER2. Several issues about its optimal use,mechanism of action or resistance still await convincing answers. Results of large-scale randomized trials and preclinical study might answer these questions. This review summarizes current knowledge about trastuzumab treatment.

The patient was a 64-year-old woman who had undergone partial enterectomy for a small intestinal tumor in August 2005, and gastrointestinal stromal tumor (GIST) was diagnosed. Administration of imanitib mesylate was initiated as postoperative chemotherapy in November 2005. In February 2006, a slight ground-glass opacity was noted in the right lower lobe on chest CT. In April, cough and dyspnea appeared, and non-segmental reticular ground-glass opacity was noted in bilateral lung fields. Drug-induced pneumonia associated with imatinib mesylate was suspected based on the clinical course, and administration of imatinib mesylate was discontinued. Oral administration of 30mg prednisolone was initiated, and the symptoms and shadows on X-ray films improved. The steroid dose was gradually reduced, and recovery of the patient was smooth. Imatinib mesylate is anticipated to be a good potential therapeutic drug for interstitial pneumonia because it blocks PDGF receptors. However, the risk of imatinib-induced interstitial pneumonia should be noticed.

A 55-year-old woman underwent total mastectomy and axillary lymphnode dissection in 2001. Widespread lymphnode metastasis was found histologically (26/33). Neither PgR nor ER was positive. She underwent an AC regimen and paclitaxel chemotherapy. As CEA began to rise in 2002, she was given paclitaxel and docetaxel chemotherapy sequentially. As CEA rose again in 2004, capecitabine was begun. Painful erythema of the palms and soles of the feet appeared at the end of the second cycle. After admission, severe bone marrow suppression and jaundice were found. The bilateral hands, palms and soles of the feet became bullous and erosive with desquamation. The erosive lesions began to heal with epithelization in the third week. After general conditions had improved, capecitabine was restarted at a reduced dose. This patient had continued taking capecitabine even though she noticed the occurrence of the adverse effect. Patients and doctors must share confidential information when performing chemotherapy at the outpatient clinic.

We report a case of recurrent gastric cancer with peritoneal dissemination and paraaortic lymph node metastases, successfully treated with weekly administration of paclitaxel. The patient was a 63-year-old man who underwent distal gastrectomy with lymph node dissection for advanced gastric cancer in February 2005. After the operation, adjuvant chemotherapy with S-1 was started and continued. He complained of abdominal distention, anorexia and nausea in April 2006. Therefore, paclitaxel (PTX) was administered at a dose of 60 mg/m(2)/day for 3 weeks followed by a week rest. Clinical symptoms were relieved, and abdominal X-ray findings showing intestinal obstruction disappeared after 2 courses. CT scan revealed metastatic lymph nodes were reduced after 3 courses. Grade 1 peripheral neuropathy and grade 2 leukocytopenia were noted, but no serious adverse reaction appeared. Weekly administration of PTX may be a promising regimen as second-line chemotherapy for S-1-resistant recurrent gastric cancer.

The present study investigated the efficacy and safety of weekly administration of paclitaxel (PTX) for 37 patients with advanced or recurrent breast cancer. PTX was administered at a dose of 60 mg/m(2), 6 times every 8 weeks. The mean number of treatment cycles was 2.1, and the mean number of administrations was 12.7. Response rate was 35.1%. Two patients achieved CR, 11 PR, 13 NC (3 patients of long NC), 9 PD, and 2 NE. The clinical benefit rate (CR+PR+NC) was 70.3%. Median survival time was 733 days, and median time to treatment failure was 151 days. Grade 3 or more leucopenia and neutropenia occurred in 3 of patients (8.1%), and no patients showed hypersensitivity reaction after administration of PTX. Weekly PTX (60 mg/m(2)) is one of the treatment options in advanced or recurrent breast cancer from the standpoint of palliation.

A 67-years old woman was referred to our hospital in October 1992 with thrombocytopenia and splenomegaly. A bone marrow biopsy revealed decreased cellularity, with moderately increased reticulin fibrosis and discrete dysmorphic megakaryocytes but no signs of dysplasia in the erythroid or the myeloid lineages. The karyotype of the bone marrow cells was t(12;17) (q24;q11). She was diagnosed as having agnogenic myeloid metaplasia. The patient received only blood transfusions until November 1998 when leukocytosis with immature cells started to appear. The bone marrow aspiration analysis showed increased cellularity and chromosomal analysis demonstrated the presence of t(9;22) (q34;q11) without any t(12;17) (q24;q11) abnormality. Because IFN therapy and oral administration of hydroxyurea did not show any cytological effect, administration of imatinib mesylate was started from December 2001. The Ph-positive cells as demonstrated by the FISH method had decreased to 7% by April 2003. But the t(12;17)(q24;q11) positive clones, which were observed on the first admission, again appeared in the peripheral blood, whereas Ph clones were detected in only one out of 24 cells examined. During the course of treatment with imatinib mesylate for chronic myelogenous leukemia which developed from agnogenic myeloid metaplasia accompanied with t(12;17)(q24;q11) translocation, the co-existence of two clones derived from, possibly, stem cells was identified.

An angiogenic factor, platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP), stimulates the chemotaxis of endothelial cells and confers resistance to apoptosis induced by hypoxia. 2-Deoxy-D-ribose, a degradation product of thymidine generated by TP enzymatic activity, partially prevented hypoxia-induced apoptosis. TP was expressed at higher levels in tumor tissues compared to the adjacent non-neoplastic tissues in a variety of human carcinomas. High expression of TP is associated with an unfavorable prognosis. To investigate the effect of TP on cisplatin-induced apoptosis, human leukemia Jurkat cells were transfected with wild-type or mutant (L148R) TP cDNA. Jurkat cells transfected with TP cDNA (Jurkat/TP) and mutant TP cDNA (Jurkat/TPMu) expressed high levels of TP, while Jurkat/CV cells which were transfected with a control vector did not express TP. A high TP enzyme activity was detected in Jurkat/TP cells, but not in Jurkat/CV and Jurkat/TPMu cells. Sensitivities to cisplatin of these cells were determined by MTT assay. IC50 values for cisplatin of Jurkat/CV, Jurkat/TP, and Jurkat/TPMu cells were 4.50, 14.08, 13.40 microM, respectively. Jurkat/TP and Jurkat/TPMu cells were about three times more resistant to cisplatin than Jurkat/CV cells. TP inhibited activation of caspase 3, 9 and mitochondrial cytochrome c release induced by cisplatin. These findings suggest a mechanism by which TP confers the resistance to cisplatin-induced apoptosis. Moreover, mutant TP that has no enzymatic activity also suppressed the cisplatin-induced apoptosis. These suggest that TP molecules have cytoprotective functions against cytotoxic agents.

We report on 4 children with invasive fungal infections complicated with leukemia who responded to voriconazole (VRCZ). In 3 children aged 1-6 years, the plasma VRCZ concentration was low and clinically ineffective after its administration at a dose of 4 mg/kg. Good plasma concentrations could be attained by increasing the dose to 5.3-12 mg/kg, and clinical effects were observed. In the other 13-year-old male, an adequate plasma concentration could be obtained after VRCZ administration at a dose of 4 mg/kg. Concerning adverse effects, transient visual abnormality developed in only 1 child. VRCZ may be effective and safe not only in adults but also in children with invasive fungal infection during chemotherapy for leukemia. Though the dose in adults is 3-4 mg/kg, the dose/weight in children should be higher because of the greater clearance. Since there are also individual differences in drug metabolism, the dose in children should be individually adjusted based on the plasma concentration.