A 74-year-old man was diagnosed as having Sézary syndrome in 1999. Treatment with combination chemotherapy could not completely control both the erythroderma and Sézary cells. However, treatment with oral administration of etoposide was able to maintain the patient in a good condition for about 4 years. In June 2004, he developed topoisomerase II inhibitor-related acute promyelocytic leukemia. Chromosomal analysis demonstrated abnormalities of t(1;10) (q21;q26) and t(15;17) (q22;q12) in 17 of 20 cells. Despite treatment with ATRA and combination chemotherapy, the patient died of brain hemorrhage.

We report a case of non-curatively resected gastric cancer successfully treated over 3 years with biweekly administration of paclitaxel. A 69-year-old man underwent non-curative resection with distal gastrectomy for advanced gastric cancer with remarkable lymph node metastasis on June 10, 2002. The metastatic lymph node (No. 8 a, 8 p and 12 a) linked up with the retroperitoneal node, making resection impossible. Postoperatively, he was initially treated with weekly administration of paclitaxel 100 mg/body (68 mg/m(2)) per week. However, due to grade 3 neutropenia in the first course, weekly administration was changed to biweekly administration with dose reduction to 60 mg/body (41 mg/m(2)), resulting in the continuation of paclitaxel therapy. Since then, no grade 3 or more severe adverse reactions have been observed. He has maintained NC for 3 years, and is still being treated on an outpatient basis at present. We believe that, in paclitaxel therapy for advanced gastric cancer, it is important for long-term survival to continue it perseveringly by dose reduction or change of schedule, when major adverse reactions are seen.

To explore the frequency and prognosis of neurological complications of acute lymphocytic leukemia, retrospective studies were made of patients with acute lymphocytic leukemia. Neurological complications were found in 13 of 100 patients during and after treatment. They were caused by chemotherapy in 8 patients, irradiation therapy in 2, vitamin B1 deficiency in 1, and unknown in 2. Medications primarily relevant to these complications were methotrexate in 5 patients, L-asparaginase in 2, cytosin arabinoside in 1. The patients were diagnosed as having leukoencephalopathy (8), cerebrovascular injury (4), and Wernicke's encephalopathy (1). Symptomatic epilepsy was found in one patient, and mental retardation was seen in three patients during a 2-year course of treatment. We conclude that careful management is required in the treatment of acute lymphocytic leukemia, because of the persistence of neurological complications, although their severity is decreasing with advances in treatment.

For postoperative adjuvant chemotherapy, UFT was administered to 69 cases of stage II and III colonic cancer following surgery with a radical curability of A. Among these patients, 8 developed hyperbilirubinemia. UFT administration was discontinued for those who developed overt jaundice or dermatological symptoms, experienced a relapse of an earlier asthmatic respiratory difficulty, or for those who were found with multiple hepatic metastases. For the 4 who had developed subclinical jaundice with a total bilirubin level of 1.6 to 2.2 mg/dl, UFT was combined with taurine. The combination successfully eliminated hyperbilirubinemia. All 4 are currently alive with no recurrence at this writing. Taurine ameliorates one's capacity to excrete bile, blood flow, and augments the actions of hepatocytes. It is effective in treating the hyperbilirubinemia that develops during UFT therapy.

Paclitaxel is one of the new drugs against advanced/recurrent gastric cancer. We report its efficacy and toxicity with weekly administration for advanced/recurrent gastric cancer. We administered 26 patients (postoperative/non-operation=9/17) PTX 80 mg/m(2)by 1-hour intravenous infusion once a week for 3 weeks followed by one week rest. Median PTX administrations were 2.0 cycles (range:1-22). Characteristics of the patients were median age of 62 (range: 37-78) and PS 0/1/2:2/17/7, male/female:18/8. Over grade 3 toxicities did not occur. The overall response rate was 14.3%, and the non-PD rate was 66.8%. Median time to treatment failure was 61 days and median survival time was 221 days. These results suggest that weekly PTX has modest activity with a favorable toxicity profile in patients with advanced/recurrent gastric cancer, and so this regimen may thus might be recommended in an outpatient treatment setting.

Multimodality therapy incorporated with radiotherapy, surgery and chemotherapy are used in the treatment of head and neck cancer in order to improve the local control and survival rate. TS-1, a newly developed oral antitumor agent which could achieve the same therapeutic concentration as that of 5-FU under continuous and intravenous treatment, has been used as adjuvant therapy for carcinomas in recent years. We presented our experience applying a new regimen of TS-1 and its side effects. TS-1 has been applied for head and neck carcinomas since 2001. The oral application of TS-1 has been used in 32 cases of head and neck cancer in our department since 2003, and the agent has been applied in 22 of 32 cases as adjuvant therapy. The primary sites of malignancy included hypopharyngx (7 cases), larynx (6 cases), maxillary sinus (2 cases), oropharynx (2 cases), oral cavity (4 cases), submandibular gland (1 case) and one case in which the primary site was unknown. A regimen of four-week application followed by two-week rest had been used in 6 cases in the first part of this trial. However, a high frequency of blood toxicity was found from the third week, requiring alteration of the protocol. Thus, a new regimen of two-week application followed by one week rest was thereafter used in the other 16 cases. Blood toxicity was found in 66.7% of those cases receiving a four-week application followed by two-week rest regimen. In the 16 cases receiving the two-week application followed by one-week rest regimen, only one case showed grade 2 leucopenia while continuous application for more than eight weeks was possible in 9 cases. Mild macrocytic anemia was found in some of these cases, however none of which required any necessary interruption of the treatment. Side effects other than blood toxicity, such as edema or pigmentation of lower limbs, erythema of skin and diarrhea, were found in the other cases, requiring suspension of the treatment. But the subsequent application was possible after a break or decreasing the dosage. We concluded that the new regimen of two-week application followed by one-week rest is less likely to be interrupted by the side effects and is safer to be used outpatiently, compared with the four-week application followed by two-week rest.

Metastatic activity is one parameter indicating the malignancy of tumor cells. Angiogenesis has now been extensively studied to clarify the mechanisms of tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is an angiogenic cytokine expressed by many human and animal tumors. We studied the role of VEGF in tumor growth by transfecting the VEGF gene into tumor cells and analyzing the survival period of nude mice implanted with these transfected tumor cells.

The objective of this study was to evaluate the efficacy and toxicity of gefitinib as a first-line therapy in patients with advanced non-small cell lung cancer (NSCLC).

Drug-induced allergic adverse events including rash, interstitial pneumonia and hepatic injury are often observed in a few patients treated with anticancer drugs that are 5-FU derivatives, including TS-1. In patients suspected to be liable to develop allergic reactions, the drug-induced lymphocyte stimulation test (DLST), based on the (3)H-thymidine incorporation ratio into the DNA of lymphocytes derived from the patients, is generally employed to identify drugs that could induce allergy. In this case report, we conducted the DLST on 20 healthy volunteers without TS-1 treatment in order to obtain reference data on the evaluation of TS-1-induced allergy. Even though all 20 volunteers were healthy, there were 6 positive responses to the DLST. In view of the positive response to TS-1 in healthy volunteers undergoing the DLST, it is suggested that the DLST could show a false positive response through an intracellular function that accelerates incorporation of thymidine in the lymphocytes by the salvage pathway after inhibition of DNA de novo synthesis caused by 5-FU derivative anticancer, including TS-1. Therefore, such a positive response to the drugs is considered, in fact, to be false-positive in the DLST. In view of the occurrence of false-positive results, the possibility of drug-induced allergy in patients receiving TS-1 should be carefully evaluated using a combination of other clinical examinations.

The antitumor effect of docetaxel against cultured human esophagus tumor cell lines and tumor xenografts in nude mice was investigated. In the in vitro study, docetaxel showed concentration-dependent inhibition of the growth of 4 tumor cell lines having different degrees of differentiation (T. T, TE-5, TE-9 and TE-15) with IC(50) values ranging from 0.84 to 1.68 ng/ml when exposed for 72 h. These values represent ca. 1/2,700-1/1,400 of the mean maximum plasma concentration of 2.27 microg/ml attained in the clinical setting. In addition, the activity was found to be ca. two-fold stronger than that of paclitaxel, and much more potent than fluorouracil and cisplatin. The in vivo antitumor effect of docetaxel was also investigated against xenografts of human esophagus squamous cell carcinoma H-190 (highly differentiated) and H-204 (moderately differentiated) in nude mice. Docetaxel at its Maximum Tolerated Dose (MTD) and the lower dose (4.5, 6.7 mg/kg/dose, q 4 d x 3, iv) showed a significant growth inhibition of ca. 100% against H-190 tumor, resulting in the tumor shrinkage. Paclitaxel (6.7, 10 mg/kg/dose, q 4 d x 3, iv) showed a tumor-shrinking effect similar to that seen with docetaxel. In the H-204 xenograft model, docetaxel (4.5, 6.7, 10 mg/kg/dose) exhibited a dose-dependent effect in delaying the tumor growth, while paclitaxel failed to suppress the tumor growth even at its MTD. These results demonstrated that docetaxel has potent antitumor efficacy against human esophagus tumor cells, leading to the expectation that it will be useful as a therapeutic agent for esophagus cancer.

We present a 12-year-old girl with acute lymphoblastic leukemia (ALL) complicated by osteonecroses of the bilateral tali. She was diagnosed as having ALL at 11 years old and was classified as extremely high risk ALL according to the criteria of Japan Association of Childhood Leukemia Study. She complained of pain around the bilateral ankles during maintenance therapy on 86-88 and 96-98 weeks. Magnetic resonance imaging study demonstrated osteonecroses of bilateral tali. Nonweight-bearing (crutches and wheelchair) over 1 year did not improve osteonecrotic lesions. She had all of the recently identified risk factors for osteonecrosis, including higher cumulative dose of corticosteroid, female gender, age over 10 years, and specific genetic polymorphisms (2/2 enhancer repeat genotype of thymidylate synthase, C/C genotype of vitamin D receptor start site). Early indication of ALL patients predisposed to genetic, treatment-related risk factors for osteonecrosis and appropriate preventive strategy for such patients await a further multicenter study in Japan.

Sex steroid hormones such as testosterone and estrogen are involved in bone metabolism. In addition, various growth factors and cytokines also participate in the metabolism. However, their involvement remained to be determined. Androgen deprivation therapy (ADT) has a potential to induce osteoporosis and bone fracture. Their incidences clearly increase over time after the therapy. Bisphosphonate treatment is clinically expected for improvement of bone lesion induced by ADT, which will be determined by future clinical studies. Androgen replacement therapy (ART) has not been established for bone-related symptoms and findings in partial androgen deficiency of the aging male. Although evidence that ART may have favorable clinical effects on bone pathology has been accumulated, further studies including those for drug preparations should be needed.

The management of conjunctival malignant melanoma remains controversial. Interferon-beta (IFN-beta) is a well-known antineoplastic agent against cutaneous malignant melanoma.

A 77-year-old man suffered from acute pancreatitis during the treatment of relapsed acute promyelocytic leukemia with As2O3. He presented with epigastralgia on day 25 during the treatment with As2O3. Pancreatic enzyme levels were elevated and the computed tomography scan of the abdomen showed swelling of the pancreas. As acute pancreatitis due to As2O3 was suspected, As2O3 was discontinued. Intravenous gabexate mesilate was administered, and the pancreatitis improved. Acute pancreatitis should be considered as a possible complication during treatment with As2O3.