We report a NSCLC patient effectively treated with anti-cancer agents on an outpatient basis despite chemotherapy with carboplatin and docetaxel, he relapsed after achieving a transient response. Combination chemotherapy with gemcitabine and vinorelbine administered every three weeks in an outpatient clinic caused the lung cancer volume to reduce remarkably. This regimen was well tolerated and suitable for outpatients. Its usefulness as a second line chemotherapy in the treatment of NSCLC should be investigated.

Management of the side effects of chemotherapy in cancer patients is important because side effects can affect the tolerability and continuation of therapy, in addition to lowering the quality of life of patients. A significant efficacy of serotonin receptor antagonists against nausea and vomiting due to cancer chemotherapy, and granulocyte colony-stimulating factor against neutropenia secondary to chemotherapy, has been recently demonstrated. New chemoprotective drugs have been developed, such as amifostine for cisplatin-induced nephrotoxicity and neurotoxicity, and dexrazoxane for cardiac toxicity due to anthracyclines. Antiviral agents including lamivudine and interferons suppress virus replication, preventing the development of fulminant hepatitis during chemotherapy in cancer patients who have chronic hepatitis B infection. Various supportive therapies have resulted in the advance of cancer chemotherapy.

A 54-year-old man was referred to our hospital because of petechiae and pancytopenia. Bone marrow aspiration showed a normocellular marrow with 92.4% promyelocytes. PML/RAR alpha mRNA was detected by reverse transcription polymerase chain reaction. On the basis of above data, a diagnosis of acute promyelocytic leukemia (APL) was made, and treatment with all-trans retinoic acid (ATRA) at a dose of 60 mg/day was begun. Fourteen days after the start of treatment, the patient developed paralytic ileus, accompanied by hyperleukocytosis, high fever, renal dysfunction and elevation of the serum FDP level. There was no evidence of infection. At this time, retinoic acid syndrome was suspected, and therefore steroid pulse therapy was started, which led to an improvement of the symptoms within four days. This case suggests that ATRA may have an adverse effect on the small intestine, causing paralytic ileus.

5'-Deoxy-5-fluorouridine (5'-DFUR), an oral fluorinated pyrimidine carbamate, is widely used in patients with gastrointestinal and breast cancers because of its effectiveness. However, in bladder cancer, response rates have only been reported in Phase II clinical trials. Therefore, we conducted a prospective randomized trial to investigate chemoprophylactic effect of 5'-DFUR against recurrence of superficial bladder cancer after transurethral bladder tumor resection (TUR-Bt). The subjects were grouped as follows: 1) 5'-DFUR group (n = 31), received 600 mg/day of 5'-DFUR starting 2-3 weeks after TUR-Bt for 2 years; and 2) control group (n = 31) received no 5'-DFUR. Although there was no significant difference between groups, the cumulative recurrence rates was more favorable in the 5'-DFUR group (p = 0.256) than in the controls. Results according to cancer factors showed that, in patients with G2 based on grading, those in the 5'-DFUR group tended to have a lower recurrence rate than the control group (p = 0.070). There was a 40% incidence of adverse drug reactions (12/30 patients), primarily slight gastrointestinal symptoms which disappeared or improved with drug discontinuation. The results of the present study suggest that 5'-DFUR might be the choice of treatment to prevent recurrence of superficial bladder cancer.

To reduce the number of patients treated at low and biologically inactive doses in phase I trials of anticancer agents, attempts to decrease the number of patients per dose level and to conduct a larger dose escalation have been made. Among them, accelerated titration designs were proposed and evaluated by simulation; designs 2 and 4 were reported to be acceptable (J Natl Cancer Inst 89: 1138-1147, 1997). Both designs 2 and 4 included only one patient per cohort during the initial accelerated phase. Dosage steps for the accelerated phase were defined using the modified Fibonacci method for design 2 and 100% escalation for design 4, respectively. The accelerated phase continued until one patient experienced dose-limiting toxicity or two patients experienced grade 2 toxicities. Dose escalation was conducted based on the information from the first course in design 2 and from the first three courses in design 4. In the simulation, both designs successfully reduced the total number of patients and the number of undertreated patients without increasing the number of overtreated patients. However, the safety of design 4 was assured as long as all patients received three courses of chemotherapy, which is unusual in phase I studies in Japan. Decision-making on dose escalation based on the information on toxicity in three courses might be cumbersome. Therefore, in Japan, design 2 would be recommended among the proposed accelerated designs. The performance of the design should be investigated by applying it to actual phase I studies and by evaluating the number of undertreated and overtreated patients.

A randomized crossover study between azasetron alone and azasetron combined with dexamethasone was performed to investigate the prevention of nausea and vomiting due to chemotherapy including cisplatin in patients with advanced head and neck carcinoma. The results indicated that the combination therapy with dexamethasone was more effective than azasetron alone in preventing nausea on days 1 through 5 after the administration of cisplatin and was significantly superior to azasetron alone on days 2 and 3. In addition, complete response (no vomiting) and the antiemetic and antinausea efficacy of combination therapy with dexamethasone on day 2 was significantly superior compared to azasetron alone. No adverse effect from either antiemetic therapy was observed in this study.

We discuss the basic concept of the continual reassessment method (CRM) and some modifications. The CRM has been proposed as alternatives of traditional cohort design for phase I trials in cancer. To focus on the dilemma between ethical concern and scientific purpose, we review the requirement for the phase I settings and the issues of the traditional cohort design. Then, CRM is introduced so that the essential feature is in the sequential (continual) selection of a dose level for next patients based on the dose-toxicity relationship and in updating the relationship based on patients' response date using Bayesian calculation. Finally we discuss both advantages and pitfalls in practice.

The expression of topoisomerase II alpha (Topo II alpha) was investigated in six human glioma cell lines as a function of doubling time, cell cycle distribution, and sensitivity to an antineoplastic agent, etoposide (ETP). The Topo II alpha level was determined by immunohistochemical and flow cytometric studies using monoclonal antibody, 8D2, specific for Topo II alpha. In all cell lines, the Topo II alpha level correlated directly with sensitivity to ETP, but not with doubling time or percentage of cells in any phase of the cell cycle. These findings suggest that the cytocidal activity of ETP may be mediated by qualitative and quantitative changes in Topo II alpha in human glioma cells. We speculate that better knowledge of Topo II alpha expression in surgical specimens may lead to more individualized use of ETP in patients with malignant glioma.

There is one of the big problems that endocrine therapy for prostate cancer causes to induce secondary osteoporosis. The risk factors and future treatments for osteoporosis were investigated.