Systemic chemotherapy has not seen widespread use in the treatment for hepatocellular carcinoma (HCC). Recently, it was reported that combination treatment of 5-fluorouracil (5-FU) and interferon (IFN)-alpha was effective for non-resectable HCC. The effect of 5-FU treatment is influenced by the activities of pyrimidine catabolic enzymes. The aim of this study was to investigate which IFN-alphais most effective in combination therapy via downregulation of dihydropyrimidine dehydrogenase (DPD).

Cytotoxic drug-induced emesis is the side effect most feared by cancer patients. The Acute emesis has become well controlled by the emergence appearance of 5-HT3 receptor antagonist, but control of delayed emesis (DE) is insufficient. The mechanism of DE is different from acute emesis,and the existence of a mediator different from serotonin is contemplated. There were some reports suggesting the role of substance P (SP) and its receptor, neurokinin receptor 1 (NK 1), in the development of emesis.

Monitoring the adverse reaction patterns specific to individual patients is important to avoid subsequent reactions. Gynecologic cancer chemotherapy is often implemented repeatedly with an altered protocol during prolonged terms. The purpose of this study was to develop and assess the efficacy of a worksheet that pharmacists can use to analyze adverse reaction patterns in individual patients with gynecologic chemotherapy. The worksheet which we developed consisted of multiple sections. One section is for necessary drug information for the proper use of antineoplastic agents. Another section is for the following items recorded by the pharmacists: a) patients' basic information such as stage of disease and protocol, b) state of implementation and break of chemotherapy and supportive therapy on calendar, and c) laboratory data and symptoms. We arranged the last item below the calendar and enabled pharmacists to easily assess individual adverse reactions coupled with the treatment course. Reviews of the developed worksheet indicated that the worksheet led to the convenient detection of individual adverse reaction patterns and effective prevention of additional adverse reactions. This monitoring sheet covering long-term chemotherapy which was designed to predict individual adverse reaction patterns will improve the individualization and safety of gynecologic chemotherapy.

We report herein on two rare cases of newly diagnosed chronic myeloid leukemia, which developed early blastic transformation within a year of imatinib treatment. Case 1 is a 22-year-old Japanese female, who underwent gradual blastic transformation with the increase of a resistant clone, which cytogenetically evolved right after she reached complete hematologic remission. Case 2 is a 24-year-old Japanese male, who underwent sudden transformation after 8 months treatment with imatinib mesylate following complete cytogenetic response. Although a sudden blastic transformation is extremely rare, the occurrence of such events even among the low-risk, good responding patients highlights the need for continued, rigorous monitoring by sensitive analysis, such as quantitative PCR. In order to accomplish the early eradication of minimal residual disease, the therapeutic strategy for chronic myeloid leukemia has to be defined in the era of imatinib, considering the application of allogeneic stem cell transplantation, which is currently the only curative treatment.

Methotrexate (MTX) is a major cause of treatment-related acute neurotoxicity. We report on clinical and imaging findings of reversibly restricted diffusion in a patient with transient encephalopathy after high dose MTX therapy for osteosarcoma. During the chemotherapy, a 19-year-old man was introduced for the evaluation of consciousness disturbance. Neurological examination revealed confusion, inability of speak at the onset On next day, there were still difficulties in swallowing and phonation, and furthermore deep tendon reflexes were hyperactive in bilateral lower limbs with positive Babinski responses bilaterally. By the 6th day, findings at neurological examination were completely normal. Initial imaging on presentation was performed using MRI. Diffusion weighted MRI clearly indicated areas of restricted diffusion within both centrum semiovale. These abnormalities were confirmed by the diffusion tensor (DT) technique (ADC and FA map). The follow-up MRI examinations using same protocol showed resolution of the ADC and FA abnormalities but increasing T2-signal changes. Neither contrast enhancement nor atrophy was encountered. Early detection of MTX white matter injury by DT image has the potential to alert the oncologist and neurologist to this event and provide a technique by which treatment of neurotoxicity can be monitored.

The most fatal complication in trastuzumab therapy for breast cancer is cardiac disfunction. It can be classified two patterns, early onset type and late onset type. This complication often becomes severe, but it is reversible if appropriate steps are taken. In treating patients with trastuzumab, their cardiac function must be checked by echocardiogram every three months.

An 85-year-old man, who had undergone right hemicolectomy and partial hepatectomy for caecum cancer with liver metastasis, was diagnosed with recurrent multiple liver metastasis 10 months after surgery. TS-1 administration at a dose of 80 mg/day induced grade 3 anorexia, and after complete recovery from the adverse reaction, it was converted to a low-dose TS-1 administration at 40 mg/day. This treatment reduced the diameter of the liver metastasis and was continued for ten months without any adverse reaction. Pharmacokinetic analysis in this patient on low-dose TS-1 showed that Cmax and AUC of 5-chloro-2,4-dihydroxypyridine (CDHP) were equivalent to the values reported in cancer patients with normal renal function receiving standard-dose administration. TS-1 therapy may provide a safe and effective alternative to chemotherapy for elderly patients with advanced colorectal carcinoma. Pharmacokinetic analysis could be useful for determining the ideal dose of TS-1.

Vinorelbine (VNB) is one of new semi-synthesized vinka alkaloids developed in France, of which anti-tumor activity is susceptible mainly to non-small cell lung cancer and breast cancer. Moreover, its clinical efficacy has been noted from single-agent therapy or combination therapy with taxanes. It is assumed that VNB selectively acts on tubulin which elaborates microtubules, strands the cells at G 1 phase and interferes with the mitosis. VNB has unique anti-tumor activity as an antimicrotubule agent and is expected to be available for treatment of multi-drug resistant tumors. In this report, we demonstrate that VNB, as an antimicrotubule agent, induces apoptosis in breast cancer cell line, MX-1 via a mitochondrial pathway.

Tailor-made medicine is a key concept in achieving a successful outcome for individual patients with malignant disease. Identifying the appropriate patient, i.e., "How to select patients", is the first concept of tailor-made medicine. In recent years, molecular target drugs have been developed rapidly and over a broad spectrum. The candidate patients for drugs are selected by particular biomarkers based on theoretical evidence. Moreover, conventional individualized methods such as TNM classification, pathological findings and patient background including performance status, and organ functions, are also important to correctly identify the patients. Identifying the appropriate therapy, i.e., "How to treat", is the next concept. Drug sensitivity tests and prediction models using DNA micro array are still under development and not available at bedside. Chemotherapy drug dosages are adjusted according to body surface area with a lack of scientific data. There have been some attempts to establish calculation formulas for modification of drugs. The Calvert formula is the best-known, however, it may not be used correctly in Japan because of the difference in the methods for estimating creatinine as well as ethnic differences. pharmacogenomics/pharmacogenetics is the front-line approach of modern chemotherapy that analyzes genomic information and pharmacokinetic/pharmacodynamic findings. This approach is achieving adaptable results for cancer treatment practice. Finally, for tailor-made medicine, we must develop genomic approach in both evaluating tumor characteristics and establishing adequate therapy, and have to combine all possible information including conventional TNM classification and pathological findings.

Herceptin (Trastuzumab) is a humanized recombinant monoclonal antibody that binds the extracellular domain of the human epidermal growth factor receptor 2 (HER2) and is used in the treatment of patients with HER2 overexpressing metastatic breast cancer. Treatment with Herceptin is generally well tolerated. At times, however, it exerts cardiac toxicity especially when used in combination with anthracyclines. We evaluated cardiac function before and after Herceptin treatment in nine patients with metastatic breast cancer by echocardiography, measuring ejection fraction (EF) and deceleration time (DcT). EF was significantly reduced after treatment(P<0.05). Although the present study failed to show significant changes in DcT, definite diastolic disturbance of the left ventricle did occur in a couple of patients. We conclude that cardiac dysfunction may be a common side effect of Herceptin even in early stages of treatment and that echocardiography will be a useful means of monitoring cardiac function in these patients.

We studied the efficacy and safety of docetaxel (DOC) for elderly breast cancer patients. Between September 1997 and June 2003, five consecutive women with advanced breast cancers who were 75 years of age or older received DOC at a dose of 60 mg/m(2) every three weeks. No premedications to prevent hypersensitive reactions and fluid retention by DOC were given. The number of DOC dosages per case was 5-16 times (12 times the median) and the relative dose intensity (RDI) was 80-100% (95% of medians). Objective partial responses were observed in all patients. The median time to partial response was 21 days (range: 21-50 days). The median time to treatment failure was 12 months (range: 5-22 months). The grade and the frequency of major side effects were the following: leukocytopenia of grade 3 (80%), edema of grade 2-3 (40%), and alopecia of grade 2 (100%). It was concluded from these findings that DOC could be safely and effectively administered to elderly advanced breast cancer patients.