Recombinant human interferon-beta in the treatment of condylomata acuminata.

The number of clinic consultations for condylomata acuminata (genital warts) has increased substantially during the last 30 years. Most infections produce benign lesions but a few types may be associated with cervical and penile cancers. Interferons (IFN) have shown antiviral properties to these infections and IFN-beta in particular has demonstrated a specific cytopathic effect in humans. A total of 124 patients with condylomata acuminata, the majority of whom had failed previous therapy, were treated intralesionally with either recombinant human interferon-beta la (r-hIFN-beta-1a) or placebo. Up to 6 lesions were treated in each patient, and injections were made 3 times per week for a total of 9 injections. The patients were then followed up for 3 months. Efficacy assessments at all time points (day 19, week 6 and month 3) showed a clear advantage for the r-hIFN-beta-1a interferon-beta treatment. Patients receiving r-hIFN-beta-1a showed a greater proportion of treatment success in terms of the complete or partial reduction (at least 50%) of the total area of the treated lesions. The treatment was also well tolerated. Headache, flu-like symptoms and asthenia were more common in patients receiving r-hIFN-beta-1a, but these adverse events were generally mild in severity and rarely led to patient withdrawal. It was concluded that r-hIFN-beta-1a has good efficacy in condylomata acuminata, and therefore presents a useful therapeutic alternative in this hard-to-treat condition.

A phase II study of recombinant interferon-beta (r-hIFN-beta 1a) in combination with 5-fluorouracil (5-FU) in the treatment of patients with advanced colorectal carcinoma.

The combination of 5-fluorouracil (5-FU) and interferon-alpha (IFN-alpha) has reported activity in the treatment of advanced colorectal carcinoma. Laboratory studies of IFN-beta suggest that this agent may offer theoretical advantages over IFN-alpha in combination with 5-FU. A total of 27 patients with advanced or recurrent colorectal carcinoma were treated in a non-randomized open phase II study with a combination of 5-fluorouracil (750 mg m(-1) daily for 5 days as a continuous intravenous (i.v.) infusion followed, from day 15, by i.v. bolus 750 mg m(-2) every 7 days) and recombinant interferon-beta [r-hIFN-beta-1a; 9 MIU (total dose) by subcutaneous injection from day 1 on every Monday, Wednesday and Friday throughout the treatment period]. Toxicity was less than that seen with this schedule of 5-FU in combination with IFN-alpha. Among 21 evaluable patients, four objective responses were seen. Recombinant human interferon-beta-1a in combination with 5-FU is an acceptable regimen in terms of toxicity. However, the study did not demonstrate a superior response rate when compared with previous reports of treatment with 5-FU alone or in combination with IFN-alpha.

Effects of interleukin 6 administration on platelets and haemopoietic progenitor cells in peripheral blood.

Platelet numbers and circulating haemopoietic progenitor cells were examined in 12 patients with advanced malignancies who were receiving recombinant human interleukin-6 (rhIL-6) as part of an investigation of its thrombopoietic effects. Patients received recombinant glycosylated IL-6 by daily subcutaneous injection for 7 consecutive days in doses of 1, 3 or 10 micrograms/kg/day. Platelet numbers increased reaching a peak on days 12-15 with a mean on day 15 of 198.1% of pre-treatment values. This was accompanied by a significant fall in the mean platelet volume (mean decrease of 10.6%, P = 0.0044). No significant correlation was seen between the IL-6 dose and the change in platelet number. No significant differences were observed between pre- and post-treatment levels of circulating erythroid burst-forming units (E-BFU) and granulocyte macrophage colony-forming units (GM-CFU) but a small significant increase was seen in circulating primitive progenitor cells measured in a plastic-adherent (P delta) assay (P = 0.025). As positive controls, a group of patients treated with cyclophosphamide/G-CSF showed significant increases in GM-CFU (P = 0.018), E-BFU (P = 0.018) and P delta progenitors (P = 0.028). These data suggest that the thrombopoietic effects of IL-6 are mediated at a relatively late stage via effects on megakaryocyte differentiation, with a relatively small effect on circulating haemopoietic progenitors.

The acute phase protein response in patients receiving subcutaneous IL-6.

IL-6, tumour necrosis factor-alpha (TNF-alpha) and IL-1 are thought to be the key mediators of the acute phase response although much of the evidence is based on in vitro studies. It is not clear to what extent each of the acute phase proteins are regulated in vivo by each of these cytokines. The aim of this study was to examine the effects of IL-6 treatment in eight patients with cancer on the concentrations of an extensive range of positive and negative acute phase proteins. It was part of a larger investigation to assess the value of IL-6 in the management of chemotherapy-induced thrombocytopenia. IL-6 was administered by a daily subcutaneous injection for 7 days at a dose level of 1, 3, or 10 micrograms/kg/day. Increases in the positive acute phase proteins, serum amyloid A, C-reactive protein, alpha 1-acid glycoprotein, alpha 1-antichymotrypsin, haptoglobin, alpha 1-antitrypsin, fibrinogen, complement component C3, and caeruloplasmin, were observed, with the greatest incremental changes and fastest responses being seen for C-reactive protein and serum amyloid A protein. The negative acute phase proteins transferrin, transthyretin and retinol binding protein all fell to a nadir within 48-96 h after the first IL-6 injection. Increases in complement component C4 were only found in two patients, which may be related to the increase in circulating TNF-alpha concentrations found only in these patients. This study has therefore shown that IL-6 is capable of causing changes in the majority of acute phase proteins in vivo. Although secondary induction of TNF-alpha was not observed in the majority of patients examined, it is still possible however that other cytokines involved in regulation of the acute phase response, such as IL-1, may have been induced and contributed to the overall response.

Lipid profile in 100 men with moderate hypertension treated for 1 year with atenolol or hydrochlorothiazide plus amiloride: a double-blind, randomized study.

A double-blind randomized study comparing the effects of 1 year's treatment with atenolol (A) 50 mg or hydrochlorothiazide 25 mg plus amiloride 5 mg (Moduretic (M)) on the lipid profile was performed in 100 hypertensive men (mean age 47, range 22-64 years). After 4 weeks' wash-out and 4 weeks on placebo therapy subjects were randomized to either A or M therapy and followed up every third month for 1 year. If the diastolic blood pressure (DBP) was greater than or equal to 95 mmHg at a subsequent visit, the doses were doubled (n = 17 for A and n = 12 for M) and, if DBP was still greater than or equal to 95 mmHg on double dose, nifedipine 20 mg b.d. was added (n = 15 for A and n = 27 for M, p less than 0.05). The lowering of heart rate (p = 0.0001) and DBP (p = 0.005) was more pronounced with A after 1 year. During that time no significant treatment differences were noted for total cholesterol, low-density lipoprotein (LDL) cholesterol or apoproteins A and B. High-density lipoprotein (HDL) cholesterol decreased from a mean of 1.19 (+/- 0.36) mmol l-1 to 1.13 (+/- 0.35) with A, and increased from 1.14 (+/- 0.30) mmol l-1 to 1.22 (+/- 0.28) with M, and this treatment difference was significant (p = 0.0002). The triglycerides increased from 2.0 (+/- 1.2) mmol l-1 to 2.3 (+/- 1.6) in the A group and did not change with M treatment (p = 0.02) for treatment difference). In view of similar effects on cholesterol, LDL cholesterol and apoproteins, the prognostic importance of the observed treatment differences on HDL cholesterol and triglycerides remains to be established.