A phase III randomized, double-blind, placebo-controlled trial of gabapentin in the management of hot flashes in men (N00CB).

INTRODUCTION: Hot flashes represent a significant problem in men undergoing androgen deprivation therapy. MATERIALS AND METHODS: Via a prospective, double-blind, placebo-controlled clinical trial, men with hot flashes, on a stable androgen deprivation therapy program for prostate cancer, received a placebo or gabapentin at target doses of 300, 600, or 900 mg/day. Hot flash frequencies and severities were recorded daily during a baseline week and for 4 weeks while the patients took the study medication. RESULTS: In the 214 eligible patients who began the study drug on this trial, comparing the fourth treatment week to the baseline week, mean hot flash scores decreased in the placebo group by 4.1 units and in the three increasing dose gabapentin groups by, 3.2, 4.6, and 7.0 units. Comparing the three combined gabapentin arms to the placebo arm did not result in significant hot flash differences. Wilcoxon rank-sum P values for change in hot flash scores and frequencies after 4 weeks of treatment were 0.10 and 0.02, comparing the highest dose gabapentin arm to the placebo arm, respectively. The gabapentin was well tolerated in this trial. CONCLUSION: These results support that gabapentin decreases hot flashes, to a moderate degree, in men with androgen ablation-related vasomotor dysfunction.

Effect of dose fractionation on the enhancement by radiation or cyclophosphamide of artificial pulmonary metastases.

Thoracic irradiation or cyclophosphamide (CP) treatment of mice before an i.v. injection of tumour cells enhances the number of lung colonies produced by a factor of up to 100+. The effect of fractionation of the X-ray or CP dose on this phenomenon was investigated in several ways.The dose-response curve for the number of lung colonies as a function of the dose of thoracic irradiation was linear, and the degree of enhancement was independent of the number of tumour cells injected. Splitting a dose of 1,000 rad into 2 equal fractions separated by times varying from 1 to 24 h gave the same enhancement as that produced by a single dose of 1000 rad. Similarly, fractionation of 1000 rad into 5 × 200 rad, or 2000 rad into 5 × 400 rad (each interval between fractions being 3 h) had no effect on the radiation enhancement of colony formation.A single dose of 200 mg/kg of CP was compared with 3 doses of 66·7 mg/kg (each dose separated by 12 h) and with a continuous infusion of 200 mg/kg given over 24 h. In this case, fractionation and infusion produced a small reduction in the CP-induced increase, but the factor of colony enhancement compared to control mice remained >100.These data emphasize the potential hazard of prophylactic treatment of pulmonary metastases by X-rays or CP in clinical situations in which control of the primary tumour is not achieved.

The effects of single and multifraction radiation courses on the mouse spinal cord.

Thoraco-lumbar spinal cord segments of C3H mice were irradiated with 250 kVp x rays and the acute and late effects of several variables were compared: single and multifraction radiation courses; changes in the length of irradiated spinal cord; and multifraction studies in which three-week and three-month splits were compared to a continuous radiation course. A scoring system for assessing the degree of radiation-induced myelopathy was devised, using a scale ranging from 1.0 (loss of rear limb reflex extension) to 4.0 (paraplegia). A significant increase in severity of spinal cord radiation injury was noted when single doses were compared to equal doses given in 10 consecutive fractions. Increasing the irradiated segment from 6 to 12 mm was also associated with more severe and earlier radiation cord injury.

Long-term effects on external radiation on the pituitary and thyroid glands.

Chronic damage following external irradiation of the normal pituitary and thyroid glands, delivered incidentally during radiotherapy of neoplasms of the head and neck may be more common than has been appreciated in the past. A case of a child who developed pituitary dwarfism 5 1/2 years after radiation therapy has been delivered for an embryonal rhabdomyosarcoma of the naso-pharynx is described. A review of similar cases from the literature is presented. Likewise, external irradiation of the normal thyroid gland produces a spectrum of radiation-induced syndromes. Clinical damage to the pituitary and thyroid glands is usually manifested months to years after treatment and is preceded by a long subclinical phase. A careful exclusion of these glands from radiation treatment fields is recommended whenever possible. An early detection of endocrine function abnormalities in patients receiving radiation to these glands is desirable, since appropriate treatment may prevent the deleterious effects of external irradiation of the pituitary and thyroid glands.

Megavoltage irradiation in the treatment of gliomas of the brain and spinal cord.

Curative radiotherapy was attempted in treating 256 patients with unresected or partially excised gliomas of the brain and spinal cord. Survival decreased with increasing age, reflecting the different incidences of tumor types in various age groups. Actuarial 5-year survival ranged from 85% for cerebellar astrocytomas, to 47% for medulloblastomas, to 41% for cerebral hemispheric astrocytomas, and 0% for glioblastoma multiforme. Further improvements in survival utilizing radiotherapy are unlikely until new adjuncts are developed, for higher radiation doses may lead to a disproportionate increase in radiation complications.