Mucositis induced by chemoradiotherapy is one of the serious side effects of cancer therapy for oral cancer. It is caused by toxic free radicals(activated oxygen)produced by these therapeutic modalities. Rebamipide is a novel anti-ulcer drug which possesses various cytoprotective activities such as free radical scavenging, induction of prostaglandin-E and acceleration of ulcer healing. We report the results of a pilot study on rebamipidegargle for inhibition of mucositis induced by chemo-radiotherapy.

The frequency of polymorphisms of CDA was analyzed and the correlation between polymorphisms of CDA and toxicity was evaluated. CDA*3 genotype strongly influenced the metabolism of the drugs and patients with CDA*3 homotype experienced severe toxicity, and the frequency differed among persons of different ethnic origin. Ethnic differences in PK and PD were demonstrated by common arm trials in USA and Japan. Pharmacogenomic differences which determine them should be more intensively been studied.

We analyzed the correlation between serum zinc levels and taste disturbance, and between patient backgrounds and serum zinc levels or taste disturbance, and evaluated the effects of polaprezinc oral disintegrating tablets on taste disturbance in 29 patients with lung cancer and one patient with malignant pleural mesothelioma who were receiving chemotherapy. Taste disturbance developed in 11 (36.7%) out of 30 patients. Serum zinc levels significantly correlated with taste disturbance (p=0.0227). Serum zinc levels were significantly lower (p=0.0235) and taste disturbance tended to be more frequent (p=0.0625) in males. Polaprezinc improved taste disturbance in 5 of 8 patients.

The feasibility and anti-tumor activity of gemcitabine (GEM) as postoperative adjuvant chemotherapy were evaluated retrospectively. Between September 1998 and June 2007, patients with resected invasive pancreatic cancer (stage III, IVa, IVb) were given adjuvant chemotherapy with GEM (GEM group, n=10) or did not receive chemotherapy (n=11). Started the administration of GEM 38.5 days after surgery, and the mean duration was 15.4 months. Grade 3 or 4 adverse event was not observed in the GEM group. There was a significant difference in overall survival between the GEM group and the no-chemotherapy group (p=0.037), but there was no significant difference in disease-free survival between the two groups. Adjuvant chemotherapy with GEM was feasible and showed a benefit in patients with invasive pancreatic cancer.

Cardiac tamponade is an emergency situation that warrants immediate evacuation of the pericardial fluid. Since the fluid tends to recur only by pericardiocentesis, various agents have been instilled into the pericardium to promote adhesion and obliteration of the cavity. Comparative studies of sclerosing agents for the management of malignant pericardial effusion include that comparing the Bleomycin group and non-administered group (JCOG) and another comparing bleomycin and doxycycline in 1996. Both studies recommended Bleomycin to control malignant pericardial effusion. Although instillation of drugs into the pericardium are reportedly safe, paracentesis or tube pericardiostomy are sometimes associated with an incidence of complications, some of which are fatal. These complications are assumed to occur in about 3% of the cases, even if an experienced physician proceeds using an echo guide. Though bleomycin is the recommended drug for the initial sclerosing agent in malignant pericardial effusion, physicians should consider the status and the prognosis of each case in the treatment of malignant pericardial effusion.

One of the specific forms of progression of malignant tumors of the central nervous system is meningeal dissemination. Meningeal dissemination is a condition in which tumor cells migrate to the brain surface and sub arachnoid space via cerebrospinal fluid and then infiltrate there. This condition can arise from both primary and metastatic brain tumors, with reported incidences of 4.2% for primary tumors and 5.1% for metastatic tumors. Meningeal dissemination frequently arises from germinoma, medulloblastoma, ependymoma and glioblastoma in cases of primary brain tumors and frequently arises from breast cancer, lung cancer and gastric cancer in cases of metastatic brain tumors, known as meningeal carcinomatosis. The prognosis of meningeal dissemination is poor, and conventional treatments such as systemic chemotherapy and radiation therapy are ineffective. Intrathecal infusion of anti neoplastic agents is one of the options for treatment of meningeal dissemination. The advantage of intrathecal chemotherapy is that the anti neoplastic agent is rapidly diffused in the sub arachnoid space, and its duration of activity is long due to its slow clearance and metabolism. Routes of administration include infusion into the lateral ventricle by puncture of the Ommaya reservoir, infusion into the sub arachnoid space by lumbar puncture, or both of these procedures performed alternately or simultaneously, and methods of infusion include bolus injection and ventriculo lumbar perfusion. Commonly used drugs include methotrexate (MTX), cytarabine (Ara-C), and 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)- 1-nitrosourea hydrochloride (ACNU), and some new drugs have also begun to be used clinically. Although there are differences depending on the histological type of the tumor, the anti neoplastic agent administered and the method of administration, the response rate is about 40-80% and mean survival time is about 4-25 months. Although side effects of the anti neoplastic agents are not as severe as with agents used for systemic chemotherapy, specific side effects include nonspecific drug-induced meningitis or ventriculitis, transient or permanent paralysis and leukoencephalopathy. These side effects can be alleviated by reducing the dose or discontinuing the anti neoplastic agents, and a small dose of an adrenocorticosteroid is sometimes administered simultaneously. Bacterial meningitis is another complication and requires discontinuation of anti neoplastic agents, removal of the Ommaya reservoir, or systemic or intrathecal administration of antibiotic agents. Although meningeal dissemination is a rare metastatic condition with a poor prognosis, there have been some reports of successful treatment using this method, which is expected to be widely used in the future.

The efficacy of anti neoplastic agents for chest catheter pleurodesis remains controversial, and little is known regarding the optimal treatment protocol. Of the various anti neoplastic agents, bleomycin and cisplatin are preferred for intrapleural therapy in Japan, and a wide variation among institutions is evident in agent doses and medication methods for pleurodesis. In many reported trials of anti neoplastic pleurodesis, problems exist such as disease heterogeneity, small sample size and differences in response criteria, and randomized control trials (RCTs) are needed to establish evidence. The JCOG 9515 trial randomly assigned patients to either the bleomycin (BLM) arm, the OK-432 arm, or the cisplatin+etoposide (PE) arm. Among them, OK-432 was demonstrated to be more effective than BLM or PE in terms of pleural progression-free survival. Intrapleural combination therapy (chemotherapy plus biological response modifiers) appeared to be superior to either alone, and further randomized studies are warranted.

Standard therapy for advanced ovary cancer is T-C chemotherapy (paclitaxel, carboplatin) after initial cytoreductive surgery. Intraperitoneal (i.p.) chemotherapy has been studied for several decades to improve the survival rate in ovarian cancer. The results of the Gynecologic Oncology Group (GOG) 172 trial comparing i.p. vs intravenous administration(i.v.) of cisplatin and paclitaxel chemotherapy were published in 2006. It showed a survival benefit in favor of the i.p. arm. The NCI (National Cancer Institute) and GOG have conducted a meta-analysis on the past seven phase III trials comparing i.p. vs i.v. that showed significant improvement in survival. NCI advised i.p. as the treatment of choice for patients with advanced ovarian cancer optimally operated. However, there are many problems that make it difficult to compare the complex regime of i.p. arms with the control arm, including the low completion rate of the i.p. and the fact that the control arm was not the present standard chemotherapy (T-C). Although it has a possibility to become the standard therapy for advanced ovarian cancer, the optimal i.p. regimen remains unclear. Clinical trials are needed to determine the optimal drug for i.p. and optimal number of i.p. administrator in order to improve the survival rate in patients with advanced ovarian cancer.

Bortezomib, a proteasome inhibitor, has been used for patients with refractory multiple myeloma. We present a 58-year old man who had IgG-gamma-type multiple myeloma, refractory for MP (melphalan-predonisolone) and VAD (vincrisitine-doxorubicin-dexamethasone) therapy. He was complicated with reactivation of varicella-zoster virus (VZV) 4 weeks before bortezomib administration. Two weeks of consolidation treatment with standard dose valaciclovir caused VZV infection to settle down and, after a further 2 weeks, VZV remission was confirmed. Bortezomib was started at a dose of 1.3 mg/m2 with prophylactic use of valaciclovir for VZV reactivation, post-herpetic neuralgia exacerbated the following day and grade 3 neuralgia developed the following week without recurrence of skin eruption. Neuralgia improved after the cessation of bortezomib with various supportive treatments and interventions. Although the reactivation of VZV was suspicious, no apparent skin lesions were observed. Although the mechanisms of post-herpetic neuralgia and chemotherapy-induced neuropathy are different, bortezomib might enhance post-herpetic neuralgia independent of the manner of viral reactivation.

A 37-year-old woman was diagnosed with therapy-related acute promyelocytic leukemia (t-APL) in May 2006 after chemotherapy that included etoposide for ovarian cancer in November 2003. After treatment with all-trans retinoic acid in combination with chemotherapy, complete remission was attained. The patient was admitted on March 19, 2007 due to cerebral infarction and it was found that t-APL had recurred. Induction therapy with gemtuzumab ozogamicin (GO) was attempted. Molecular remission was attained without serious complication. GO is considered a promising agent to achieve molecular remission in patients with relapsed t-APL.

Oxaliplatin in combination with infusional 5-fluorouracil/Leucovorin (FOLFOX) has emerged as the treatment of choice for advanced-stage colorectal cancer. Sensory neurotoxicity is its dose-limiting toxicity. We decided to use Gosha-jinki-gan for prevention of oxaliplatin-related neurotoxicity following the report of Fushiki et al.

The efficacy of the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) was estimated clinically among breast cancer patients to select a rational chemotherapy. Twenty-five specimens of breast cancer (n=21) or lymph nodes (n=4) were investigated. Four anticancer drugs (5-Fluorouracil, Adriamycin (ADM), Docetaxel (DOC), Paclitaxel (PTX)) were estimated for CD-DST. Sixteen samples among 25 samples (64.0%) seemed to be worth estimation. The chemosensitivity values were as follows: 5-FU 30.8%, ADM 30.8%, DOC 53.8% and PTX 46.2%, respectively. Thus, CD-DST may predict the chemosensitivity with high accuracy in breast cancer patients and seems to be superior to the conventional predictors.

Early glottic carcinoma has a good prognosis compared to other head and neck carcinomas, but we must aim for larynx preservation in the treatment. Regarding T1N0, larynx preservation rates are favorable even with radiotherapy alone. However for T2N0, the treatment strategies differ in each institution, and larynx preservation rates range from 72% to 85%, and are not high enough. We conducted a study to determine the efficacy of the concurrent chemoradiotherapy with S-1 for T2N0 glottic carcinoma. In this study, 12 patients with T2N0 glottic type laryngeal squamous cell carcinoma enrolled from the year 2004 to 2006, received one reduction dose of S-1 (80 or 100 mg/day) with concomitant irradiation with a total dose of 60-70 Gy (2.0 Gy/fr). The 2-week administration of S-1 followed by one-week rest was repeated during irradiation. In terms of adverse events of Grade 3 and above, Grade 3 mucositis and dermatitis were found in 2 patients each, but there was no cancellation nor interruption of S-1 or irradiation. All patients achieved pathological CR at the time of evaluation after the primary treatment, and no recurrences have been seen yet in any of the primary sites. Concurrent chemoradiotherapy with S-1 showed efficacy in T2N0 glottis carcinoma. Further investigation of this treatment with long-term follow up results is warranted.

In this study we evaluated the efficacy and toxicity of transcatheter arterial chemoembolization (TACE) with Cisplatin (CDDP)-Lipiodol (LIP) suspension in 24 patients with advanced hepatocellular carcinoma (HCC). Eligibility criteria were as follows; unresectable HCC, age <75 years, performance status (PS) 0-2, Child-Pugh A or B and adequate heart and renal function. When TACE was performed, the catheter was placed selectively in feeding arteries of the tumors, and CDDP-LIP suspension (20 mg/mL) was injected followed by gelatin sponge particles. The direct and total effect on tumors were evaluated 3 and 6 months after TACE, respectively. As for a direct effect, complete and partial response rates were 54.2% and 25%, respectively. As for a total effect, complete and partial response rates were 41.7% and 4.1%, respectively. Grade 3/4 drug-related toxicities were as follows: thrombocytopenia (13%), appetite loss (8%) and nausea (4%). These severe side effects disappeared within 10 days after TACE. No renal and hepatic dysfunction was encountered, and no drug-related deaths occurred. TACE with CDDP suspended in LIP may provide some clinical benefits with relatively tolerable toxicities.

A 70-year-old Japanese man was re-admitted because of relapse of adenocarcinoma of the lung. He received daily administration of gefitinib as second-line chemotherapy. He was given a diagnosis of drug-induced lung disease due to gefitinib on day 6 because of hypoxemia and ground glass opacities in the bilateral lung fields. There was no response to corticosteroid pulse therapy. Continuous administration of sivelestat was intravenously added from day 9. Although mechanical ventilation was required for 10 days, lung infiltrates and hypoxia gradually improved. Sivelestat and corcicosteroid was apparently effective in this case and may be useful treatment for drug-induced lung disease due to gefitinib.

Recently, ambulatory treatment centers (ATC) are markedly increasingboth in number and scale. It is therefore important to consolidate an efficient therapeutic system. A decrease in both treatment time and waitingtime leads to not only the improvement of the quality of life (QOL) for patients but also the efficient use of personnel and running costs for medical institutions by reducingthe bed occupation rate. In ATC, 5-HT3 receptor antagonists are extensively used for high emetic risk patients. However, their high cost and prolonged treatment causes one of the problems in improvingthe efficiency of the therapeutic system when they are administered by intravenous infusion. Amongthe 4 types of 5-HT3 receptor antagonists (injections) currently available in Japan, azasetron is the only drugthat is not designated as a powerful drug and that can be administered by bolus intravenous infusion. In this study, we investigated azasetron and granisetron from the standpoint of pharmacoeconomics with a simulation model using the results of clinical studies in Japan. Accordingto the results of cost-effectiveness analysis, therapeutic and time costs per patient for azasetron 10 mgand granisetron 2 mg (calculated in consideration of both medical institutions and patients) was 8,219 and 10,193 yen, respectively. This gap was attributable to the time loss due to the difference in administration methods. The result suggests that this time loss is more significant not only for patients but also for medical staff than the loss attributable to the drugcost. Furthermore, the bolus intravenous infusion of azasetron is considered superior to the non-bolus intravenous infusion of granisetron from a pharmacoeconomic standpoint. It is desirable to choose the appropriate administration method of 5-HT3 receptor antagonists in various chemotherapy regimens for the purpose of reducingthe treatment time and promotingthe efficiency of the therapeutic system at ATCs.

To provide effective and safe cancer treatment, the medical staff must form a team with patients and their family. Pharmacists have to be responsible for verifying chemotherapy prescription orders, mixing of anticancer drugs, management of adverse drug reactions, patient education, while providing drug information and participation in palliative care. To promote pharmacists who have acquired advanced knowledge and skills, The Japanese Society of Hospital Pharmacists started and educational program and established the certification of board-certified oncology pharmacy specialists (BCOPS) and board-certified pharmacists in oncology pharmacy (BCPOP). As of November 2007, 56 pharmacists were qualified as BCOPS.

Recent progress in pharmacogenetic research has made "personalized medicine" a reality, where a suitable drug at the appropriate dosage is prescribed based on individual genetic factors. Irinotecan, an anticancer drug, is one of the models for personalized medicine, and a number of clinical studies have revealed significant associations between UGT1A1(*)28 and irinotecan toxicity. Based on the cumulative evidence, clinical tests for the UGT1A1(*)28 marker have started in the United States since 2005. However, the appropriate criteria for irinotecan dose adjustments have not yet been fully established. Since there are considerable differences in genetic polymorphisms among different ethnic groups and in approved irinotecan-containing regimens between countries, the criteria for the choice of suitable genetic markers and dose adjustments should be standardized in each country. This mini-review outlines our recent studies on irinotecan pharmacogenetics and discusses the clinical significance of UGT1A1(*)6 and (*)28 markers for personalized irinotecan therapy in Japanese cancer patients.