The efficacy of hyposensitization with a standardised extract of Dermatophagoides pteronyssinus (D. pteronyssinus) conjugated to alginate and containing known amounts of antigen P1 (Conjuvac) was tested in a double blind, placebo controlled, multi-centre study in 66 adult patients with perennial rhinitis. Patients received 11 weekly injections of increasing concentrations of Conjuvac containing from 56 x 10(1) to 448 10(3) IU D. pteronyssinus or placebo injections of the alginate diluent to some of which 5 micrograms of histamine has been randomly added. This was followed by 15 monthly injections of Conjuvac or placebo. The severity of nasal blockage, sneezing and rhinorrhoea was recorded twice daily in a diary and visual analogue assessments (VAS) made at each clinic visit. Nasal provocation testing (NPT) was performed with increasing concentrations of the same extract of D. pteronyssinus as used in the hyposensitization injections, and changes in nasal airways resistance measured by passive anterior rhinomanometry. VAS was recorded and NPT was performed on entry to the study and after the fifth, ninth and final monthly injection. Conjuvac injections were well tolerated. Large local reactions (greater than 5 cm) occurred within 30 min in only 1% of patients but later in 23%. No systemic reactions or anaphylaxis occurred within 30 min of injections, but urticaria or worsening of asthma and rhinitis was reported later in 3% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Summary The pollen of Parietaria species is a well‐recognized and important inhalant allergen in the Mediterranean area. Parietaria judaica (Pellitory‐of‐the‐Wall) is native to the U.K., flowering from June to September, but is not usually considered to be of any clinical importance by U.K. allergists. We skin tested 62 patients with a clinical history of summer seasonal respiratory symptoms and a control group of 11 patients with perennial respiratory symptoms only. Each was skin tested in duplicate with extracts of grass pollen, birch pollen, Parietaria pollen, Dermatophagoides pteronyssinus, Cladosporium, Alternaria, nettle pollen and negative and positive controls, and serum samples were collected for RAST assays for Parietaria and nettle. Eight of the 62 patients in the main group showed skin reactivity to Parietaria. Five of these eight had never visited the Mediterranean area and therefore it is possible that sensitization occurred in the U.K. Thirteen of the 62 patients were skin reactive to nettle but there was no correlation between skin reactivity to Parietaria and nettle. This supports a recent report that, despite their close botanical relationship, no antigenic cross‐reactivity exists between the two species. No correlation was seen between skin reactivity and serum RAST activity to Parietaria or nettle. It is not known whether exposure to Parietaria pollen contributes to the seasonal symptoms of the patients found to be skin reactive. None of the 11 patients in the control group was skin reactive to Parietaria.

PurposeThis study aimed to evaluate the maximum tolerated dose (MTD) and recommended phase II dose (RPTD), as well as the safety and tolerability of PF-03446962, a monoclonal antibody targeting activin receptor like kinase 1 (ALK-1), in combination with regorafenib in patients with refractory metastatic colorectal cancer.MethodsThe first stage of this study was a standard “3 + 3” open-label dose-escalation scheme. Cohorts of 3–6 subjects were started with 120 mg of regorafenib given PO daily for 3 weeks of a 4 week cycle, plus 4.5 mg/kg of PF-03446962 given IV every 2 weeks. Doses of both drugs were adjusted according to dose-limiting toxicities (DLT). Plasma was collected for multiplexed ELISA analysis of factors related to tumor growth and angiogenesis.ResultsSeventeen subjects were enrolled, of whom 11 were deemed evaluable. Seven subjects were enrolled at dose level 1, and four were enrolled at level − 1. Overall, three DLTs were observed during the dose-escalation phase: two in level 1 and one in level − 1. A planned dose-expansion cohort was not started due to early termination of the clinical trial. Common adverse events were infusion-related reaction, fatigue, palmar-plantar erythrodysesthesia syndrome, abdominal pain, dehydration, nausea, back pain, anorexia, and diarrhea. One subject achieved stable disease for 5.5 months, but discontinued treatment due to adverse events.ConclusionsThe regimen of regorafenib and PF-03446962 was associated with unacceptable toxicity and did not demonstrate notable clinical activity in patients with refractory metastatic colorectal cancer.

In a 2-year double-blind placebo controlled study an immunological evaluation was carried out on 33 patients (15 males, 18 females, mean age 29.2 years) with mite-induced perennial rhinitis who were submitted to specific immunotherapy (IT) with an alginate-conjugated extract of D. pteronyssinus. The behaviour of IgE, IgG, IgG1 and IgG4 antibodies specific to D. pteronyssinus and its major allergen Der p1 was characterized by assessment of their changes in serum, and changes in IgG in nasal secretions during the treatment. The placebo-treated patients did not show any significant variation in the levels of specific antibodies, while in the actively treated patients we found: a statistically significant decrease (P less than 0.005) of specific IgE, a statistically significant increase of specific IgG (P less than 0.005), IgG1 (P less than 0.005) and IgG4 (P less than 0.005) in serum and a statistically significant increase (P less than 0.001) of specific IgG in nasal secretions. The IgG response showed an early relative predominance of the IgG1 subclass and a late absolute predominance of IgG4 subclass, that confirmed the model of IgG4 restriction in prolonged allergen stimulation. No correlation was found between immunological and clinical data.

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