Luteinizing hormone-releasing hormone agonist (LH-RH analogue) therapy, is one of the most widely used hormonal therapies. Recently, subcutaneous injection of a new long acting 3-month LHRH analogue depot has been developed. We investigated the adverse events induced by injection of an LH-RH analogue in 82 patients (median age was 75 year old, 59-87) using our questionnaire. Forty-eight and 34 cases had been administered leuprorelin acetate (LSR) and goserelin acetate (ZLA). The presentation rate of skin reaction was 8.8% (3/34) in the ZLA group and 14.6% (7/48) in the LSR group. There was no significant difference in rate of skin reaction between the LSR and ZLA group (p = 0.5113). Eight patients had induration (6 in LSR 2 in ZLA). We also present a case of subcutaneous granuloma formation at the injection site after using the three-month type preparation of leuprorelin acetate. We should be aware of the risk of skin reactions at the injection site and monitor carefully when using an LH-RH analogue.

Despite recent progress in diagnosis and therapy, hepatocellular carcinoma (HCC) remains among the cancers with the poorest prognoses. Vitamin K (VK) have been shown to suppress the growth of HCC cells. Long-term administration of VK(2) has established its clinical safety, but it does not appear to exhibit marked anti-tumor effects when administered alone. For more effective use of VK against HCC, co-administration of VK(2) with other proven anticancer agents or development of a new VK preparation with a modified side-chain should be investigated in the future.

A number of anticancer drugs exert their effect by causing DNA damage and subsequent apoptosis induction. Reactive oxygen species (ROS), such as hydrogen peroxide (H(2)O(2)) and super oxide anion (O(2)(-)), participate in apoptosis and DNA damage induced by some anticancer drugs, however, the precise mechanism of apoptosis via ROS formation remains to be clarified. I investigated the mechanism of apoptosis and DNA damage induced by anticancer drugs, especially topoisomerase inhibitors, using human cultured cells. TAS-103, a topoisomerase inhibitor, induces apoptosis through DNA cleavage and subsequent H(2)O(2) generation mediated by poly (ADP-ribose) polymerase (PARP) and NAD(P)H oxidase activation. Doxorubicin (DOX), an anthracycline antibiotic and topoisomerase inhibitor, induces apoptosis through direct oxidative DNA damage leading to indirect H(2)O(2) generation mediated by PARP and NAD(P)H oxidase activation. DOX caused site-specific oxidative DNA damage in the presence of copper(II), which may contribute to apoptosis. These findings suggest that ROS formation plays important roles in apoptosis induced by anticancer drugs. Furthermore, these studies may provide an insight into the development of new effective chemotherapeutic drugs.

We report a patient with gallbladder cancer and multiple liver and lymph node metastases which completely responded to S-1, an oral fluoropyrimidine anticancer drug. The patient was enrolled in the "Late phase II study of S-1 in patients with advanced biliary tract cancer". A partial response was confirmed after the first two courses of S-1 monotherapy, and anti-tumor efficacy was finally evaluated as a complete response after the 5th course. S-1 was discontinued after the 18th course because of long CR, and the patient has been alive and disease-free for more than 3 years. Grade 2 anorexia, diarrhea, hand-foot skin reaction, and tasty disturbance were observed, but no grade 3 or more toxicities were noted. S-1 appeared to be effective against advanced gallbladder cancer and showed excellent tolerability.

Chemotherapy-susceptive multiple myeloma (MM) has an indication for high-dose melphalan (HDM) followed by autologous stem cell transplantation (auto-SCT). HDM was a most simple and convenient regimen among various preparatory regimens, because of rapid infusion divided over 2 days. In order to assess the potential of auto-SCT by HDM in a outpatient setting, we evaluated the toxicities of HDM compared with the ICE regimen generally applied to patients with refractory or relapsed lymphoma. We reviewed 27 cases of auto-SCT from April 2003 to December 2004. The preparatory regimen was HDM (melphalan 200 mg/m(2)) for 18 cases of multiple myeloma and ICE therapy (ifosfamide 12 g/m (2), carboplatin 1,200 mg/m(2), etoposide 800 mg/m2) for 9 malignant lymphomas. Gastrointestinal (GI) adverse events for a patient per hospital day were 0.93 for myeloma and 0.95 for lymphoma (no significant differences), with GI toxicity of more than grade 3, 0.08 and 0.12, respectively (p=0.07). Hematological toxicity was not significantly different between the 2 therapies. The clinical toxicity of HDM was milder compared to ICE, especially regarding the speculated GI-associated nutritional disorders. We thus concluded that outpatient auto-SCT could be validated first in myeloma patients treated by HDM with careful supportive treatments, thereby avoiding regimen-related severe adverse events.

Reactive oxygen species (ROS) are implicated in many disease such as inflammation, arteriosclerosis, cancer. Therefore, a water-soluble cationic metalloporphyrins with SOD activity are studied widely as antioxidant drugs. Further, liposomes are applied to drug delivery system (DDS) as drug carriers and investigated for example disposition and stability. We designed PEG modified liposomes for avoiding reticuloendothelial system (RES) and embedded cationic metalloporphyrins for DDS, evaluated antioxidant and anticancer property. Preservation of these particle size measured DLS in an in vitro system, in order to simulate in vivo conditions of flow. Result of this measurement, we found Pluronic F-68/ liposomes have a long circulation property, and avoid fusion with plasma protein. SOD activity was determined by the stopped-flow analysis and cytochrome c assay, which allowed the evaluation of k(cat) and IC(50) for the reaction with a superoxide anion radical (.O(2)(-)). Anti cancer property was measured by cell viability test. We found that F-68/ liposomes were the most effective catalyst as antioxidant and anticancer. These results revealed that porphyrin-embedded PEG-liposomes had the property of long circulation in blood and that this compound was effective as a SOD model compound with a drug carrier capacity.

The standard chemotherapy for ovarian carcinoma is paclitaxel and carboplatin concomitant therapy. This combination is so frequently administered that a carboplatin-associated hypersensitivity reaction may occur after long-term treatment. Recently, we experienced carboplatin-associated hypersensitivity reactions in three cases. They showed symptoms of tachycardia, chest tightness, and dyspnea. We report these cases that could be readministered platinum agent using the cisplatin desensitization method. This method was relatively safe and successful for patients with platinum-sensitive disease.

Favorable results of various comparative studies have been reported in recent years regarding adjuvant chemotherapy for non-small cell lung cancer (NSCLC), resulting in an increase in the number of facilities that proactively conduct adjuvant chemotherapy in Japan. In the present study, we evaluate the tolerability of a postoperative adjuvant chemotherapy regimen conducted in our facility using paclitaxel (PTX) and carboplatin (CBDCA). Thirteen patients who received weekly PTX and CBDCA as postoperative adjuvant chemotherapy were evaluated retrospectively. PTX was administered by iv drip infusion over 1 hour at 70-80 mg/m(2), followed by CBDCA at AUC= 2 by iv drip infusion over 1 hour. This was repeated on Days 1, 8 and 15, followed by a rest on Day 22. Two to 4 cycles were conducted in each patient. Patients were admitted only the first time, and treatment was thereafter conducted on an outpatient basis. The scheduled number of cycles could be completed in all but one patient who developed interstitial pneumonia 2 days after treatment. Non-hematologic toxicities observed included peripheral neuropathy in 3 patients, nausea in 2, general fatigue in 6, stomatitis in 2, and alopecia in 11. Hematologic toxicities include leukopenia in 10, but leukopenia was not febrile, Grade 3 or more severe in any of these patients. In addition, decreases in hemoglobin and thrombopenia were observed in 10 and 2 patients, respectively, but both adverse events were mild (< Grade 3) and could be controlled on an outpatient basis in all cases. Our findings suggested that adjuvant chemotherapy using weekly PTX/weekly CBDCA for NSCLC is well tolerated and can be safely conducted on an outpatient basis.

We investigated whether the deleterious side effects of chemotherapeutic agents on the physiologic functions of fish could be modulated by lactoferrin (LF). Goldfish, weighing about 25 g, were treated intramuscularly with methotrexate (MTX: 2.5 mg/kg body weight) and fluorouracil (FU: 15 or 50 mg/kg body weight) three times every other day. In control fish fed a commercial diet, MTX induced severe immunosuppression, increased the number of total bacteria and Enterobacteriaceae in the intestinal tract, and caused intestinal damage such as lowered and thickened mucosa and thinned muscularis externa, with moderate renal dysfunction. A few fish treated with MTX died. In fish injected with FU or FU plus MTX, the side effects were slightly less in comparison with those in the MTX group. Pretreatment with LF (oral administration at 200 mg/kg body weight/day) for 3 weeks reduced the deleterious side effects of MTX and FU. One intraperitoneal injection of LF (200 mg/kg body weight) immediately after the first MTX injection also reduced the side effects. These results show that LF reduces the physiologic dysfunction of fish treated with chemotherapeutic agents.

We reported a case of acute respiratory distress syndrome (ARDS) induced by docetaxel in treating lung metastases from oral cancer. The patient was an 84-year-old man who had undergone partial mandibulectomy and radical neck dissection for lower gingival carcinoma. The patient developed ARDS after docetaxel administration (40 mg/body) for multiple lung metastases.

Cetuximab, an IgG1 chimeric monoclonal antibody directed against the epidermal growth factor receptor (EGFR), has been shown to have antitumor activity against EGFR-expressing colorectal cancer (CRC). Although the activity of cetuximab monotherapy is notable,cetuximab-based combinations have conferred greater benefit, with two-fold higher response rates and nearly three-fold longer progression free-survival with cetuximab plus irinotecan compared with cetuximab alone,even in irinotecan-refractory patients. Cetuximab monotherapy should be reserved for patients who cannot tolerate combination therapy. Interestingly, consistent with other reports of both EGFR-targeting antibodies and receptor tyrosine kinase inhibitors, the severity of the rash related strongly to both response and survival. This hypothesis was tested in the EVEREST trial, in which patients with irinotecanrefractory CRC are randomly assigned to treatment with irinotecan plus cetuximab on either a conventional dose-schedule or titrated to a maximal-tolerated rash. By increasing cetuximab doses,a slightly higher skin reaction and response rate could be induced in the experimental arm. On the other hand,important phase III trials will present results in the near future (CRYSTAL and CALGB/SWOG 80405 trial). It remains to be seen if those trials can validate the encouraging data about cetuximab in the first-line treatment.