Phase III double-blind randomized trial of radiation therapy for stage IIIb cervical cancer in combination with low- or high-dose Z-100: treatment with immunomodulator, more is not better.

BACKGROUND: To evaluate the efficacy of low or high-dose immunomodulator, Z-100, in combination with radiotherapy for cervical cancer. METHODS: Between 1995 and 1999, 221 patients with stage IIIb squamous cell carcinoma of the cervix were randomly assigned to treatment with Z-100 either at 0.2 microg or 40 microg in a double-blind manner in combination with radiotherapy. RESULTS: The 5-year survival of patients with high-dose and low-dose Z-100 was 41.5% (95% CI: 31.7-51.3%) and 58.2% (95% CI: 48.7-67.7%), respectively, showing a 30% reduction in the death rate (hazard ratio: 0.670 [95% CI: 0.458-0.980], P = 0.039). Survival of high-dose group was equivalent to the 4-year survival of the radiotherapy plus hydroxyurea arm (49.7%) of GOG120 study, and that of low-dose group was similar to the survival of the cisplatin-based chemoradiation arm. The progression-free survival was also significantly improved in favor of low-dose group (hazard ratio: 0.667 [95% CI: 0.447-0.997], P = 0.048). The survival of low-dose group was similar to the survival of the cisplatin-based chemoradiation arms of the GOG120 study. CONCLUSIONS: Unexpectedly, the survival of patients with advanced cervical cancer treated by lower dose of Z-100 in combination with radiotherapy was significantly better than those treated with higher dose Z-100, which was equivalent to the survival with radiotherapy alone. The hypothesis that lower dose of Z-100 enhances the efficacy of radiation therapy is now being tested by placebo-controlled randomized trial.

Adjuvant oral 5-fluorouracil for cervical cancer: Japanese Gynecologic Oncology Group report.

Japanese women with low-stage cervical cancer receiving radical hysterectomy and radiotherapy have a good 5-year survival rate. However, women with risk factors such as nodal metastasis may benefit from adjuvant chemotherapy, which was studied in women having surgery alone or surgery plus radiotherapy. Patients having surgery alone (S) (n=623) or surgery and radiotherapy (SR) (n=919) were randomly assigned to receive or not receive oral 5-fluorouracil (5-FU) for 1 year. The effect of various factors on survival was studied by multivariate analysis. Patients who received S obtained no benefit from 5-FU, whereas 5-FU-treated SR patients had significantly better 5-year survival than those not receiving chemotherapy (P=0.043). The SR patients without nodal metastases had a better survival rate if they received 5-FU (P<0.001), whereas those with nodal metastases did not. Oral 5-FU after radical hysterectomy with radiotherapy appears useful for patients with low-stage cervical cancer who have some risk factors but not for those with pelvic lymph node metastases.

Differences in fractal structure of adult heart rate fluctuation between successive rapid eye movement sleeps: case report.

The dynamics of fractal structures of heart rate (HR) fluctuations in successive rapid eye movement sleeps (REMS) was investigated in a healthy male. Fractal analysis using a purposely-devised method was carried out at 10-min time series of HR, which were being recorded simultaneously by an electroencephalogram at night. Scaling relationships showed three slopes (alpha(s)). The mean alphas below one cross-over point (< 6.0 s), mean alpha(m) between two cross-over points, and mean alpha1 above another cross-over point (> 12.0 s) during REMS changed from 2.0, 1.0, and 0.3 in the third cycle to 2.0, 0.9, and 1.2 in the fourth cycle. The present study demonstrates the differences in multiscaled fractal structures of HR fluctuations between the successive REMS in a particular case.