Refractory pulmonary aspergillosis: compassionate trial with terbinafine.

The frequency of bronchopulmonary aspergillosis is increasing due to the growing number of patients requiring steroids or other immunosuppressive therapies. Conventional treatments are ineffective in some patients and side-effects are an important issue. The aim of this work was to evaluate the effectiveness and safety of terbinafine, a new allylamine antimycotic drug, in three immunocompetent patients affected by lower respiratory tract aspergillosis [one chronic empyema due to Aspergillus fumigatus (AF) and two chronic necrotising aspergillosis] not responsive to the usual antimycotic therapies. In in vitro and animal model systems, terbinafine is as active as amphotericin B and itraconazole. Patients received terbinafine at doses ranging from 5 to 15 mg/kg per day, according to clinical status, for 3-5 months, depending on the clinical course of the disease and compliance. In patient 1 a negative anti-AF precipitin was obtained together with eradication of AF from the pleural cavity, which allowed a successful intrathoracic myo-omento-mammoplasty. In patients 2 and 3, AF was eradicated, anti-AF immunoprecipitins decreased, and clinical and radiological findings significantly improved. On the basis of the effectiveness of terbinafine demonstrated in this preliminary work, large studies to evaluate the use of terbinafine in bronchopulmonary aspergillosis are warranted. Moreover, the drug is not associated with resistance or significant side-effects.

Terbinafine in the treatment of non-immunocompromised compassionate cases of bronchopulmonary aspergillosis.

Conventional treatments of broncho-pulmonary aspergillosis are often ineffective and result in associated side-effects. Terbinafine (a new allylamine derivative), although as active against Aspergillus in vitro as amphotericin B and itraconazole, is less effective in rodent models because of a rapid hepatic first-pass effect. As terbinafine is metabolized differently in humans, the aim of this work was to evaluate this drug, for the first time, in the treatment of seven immunocompetent patients with lower respiratory tract mycotic infections unresponsive to the usual antimycotic drugs. Diagnosis was based on identification of fungal isolates, worsening of respiratory function tests, chest radiographs and computerized tomographic (CT) scan changes, positive skin test, aspergillin precipitins and clinical history. Terbinafine was administered at doses ranging from 5 to 15 mg kg-1 day-1 depending on the clinical severity of the disease, and was given for 90-270 days depending on clinical progress and compliance. In three patients A. fumigatus was suppressed with resolution of signs and symptoms; four patients showed transitory A. fumigatus suppression with marked clinical and radiological improvement. During relapses no resistance to terbinafine was observed. No significant side-effects were detected. Terbinafine appeared to be as effective as amphotericin B and itraconazole in the treatment of bronchopulmonary aspergillosis in nonimmunocompromised patients. These preliminary results suggest that controlled studies are warranted.

Salmon calcitonin in cancer pain: comparison between two different treatment schedules.

The analgesic effect of salmon calcitonin (Calcitonina-Sandoz) was evaluated in an open study of thirty-four patients with bone metastases of a lung cancer. Two different administration protocols were used: eighteen subjects received sCT 400 IU/day for three consecutive days, while the remaining sixteen were given sCT 200 IU/day for six consecutive days. In both protocols salmon calcitonin was diluted in saline and infused intravenously in one hour. Bone, visceral and neuritic pain were evaluated by means of Huskisson's visual analog scale and Keele's pain scale. The analgesic efficacy of salmon calcitonin was also evaluated on the basis of daily consumption of analgesic drugs. Salmon calcitonin proved of extreme efficacy in the treatment of intractable pain from advanced malignancy. A higher and earlier analgesic activity was observed with sCT at the 400 IU daily dosage.