Phase I study of bortezomib and cetuximab in patients with solid tumours expressing epidermal growth factor receptor.

Bortezomib inhibits nuclear factor-kappaB (NF-kappaB). Cetuximab is a chimeric mouse-human antibody targeted against epidermal growth factor receptor (EGFR). We hypothesised that concomitant blockade of NF-kappaB and EGFR signalling would overcome EGFR-mediated resistance to single-agent bortezomib and induce apoptosis through two molecular pathways. The aim of this phase I trial was to establish the maximum tolerated dose (MTD) for bortezomib plus cetuximab in patients with EGFR-expressing epithelial tumours. The 21-day treatment cycle consisted of bortezomib administered on days 1 and 8 through dose escalation (1.3-2 mg m(-2)). Cetuximab was delivered at a dose of 250 mg m(-2) on days 1, 8 and 15 (400 mg m(-2) day 1 cycle 1). A total of 37 patients were enroled and given a total 91 cycles. No grade > or =3 haematological toxicity was noted. Non-hematological grade > or =3 toxicities included fatigue (22% of patients), dyspnoea (16%) and infection (11%). The MTD was not reached at the highest tested bortezomib dose (2.0 mg m(-2)). Efficacy outcomes included disease progression in 21 patients (56.7%) and stable disease (SD) at 6 weeks in 16 patients (43.3%). Five of the six patients with SD at 12 weeks were diagnosed with cancers of the lungs or head and neck. This combination therapy was moderately effective in extensively pretreated patients with non-small cell lung or head and neck cancers and warrants further investigation.

Genetic nature of vitiligo.

Four hundred vitiligo patients and 100 non-vitiliginous controls were studied to find out the prevalence of vitiligo in relatives of patients and controls. The difference was found to be statistically highly significant. The data reflected that there is some genetic mechanism involved in the etiology of vitiligo. Respective relatives of all forms of the disease in the vitiligo group showed a clear preponderance compared to controls. There was clustering of affected relatives in vitiligo cases compared to controls. The ratio of affected and unaffected siblings with unaffected parents or one parent affected, the ratio in the children of probands, the ratio in children of affected paternal and maternal grandparents of probands, suggest the polygenic nature of vitiligo.

A study of some important biological factors influencing infant mortality under Indian conditions.

PIP: The authors analyze the biological factors affecting infant mortality in Gorakhpur, a district in eastern Uttar Pradesh, India. The data concern 162 families living in rural, semi-urban, and urban areas and were collected in 1984. The factors considered include age of mother, age and sex of infants, family type, birth spacing, birth order, and birth weight.^ieng

Prevalence of Ocular Involvement in Leprosy in Easstern Uttar Pradesh.

A survey of 995 cases of leprosy revealed the prevalence of ocular involvement to be 275.4 per thousand. Lepromatous leprosy showed the highest prevalence. Majority of the cases were males, but prevalence of ocular involvement was higher in females. The 40-50 year age group showed the maximum prevalence. The time interval between the onset of skin lesions and the eye lesions, in majority of the cases was 5-10.

Corneal Blindness in Leprosy in Eastern Uttar Pradesh.

One hundred and eighteen cases of leprosy with ocular involvement were found to have corneal involvement out of a total 274 cases of ocular in volvement in leprosy. The common eye lesions observed were chronic conjunctivitis (54.01%), keratitis (47.07%), iritis (31.75%) and lagophthalmos (27.76%). In 38.98% of the cases, the time lag between the onset of skin lesions and corneal lesions was 5 to 15 years. The major causes, which lead to involvement of cornea, were corneal anaesthesia (116), lagophthalmos (76), ectropion (21), entropion (11) and trichiasis (4). Corneal blindness constituted 55.6% of total blindness in leprosy with ocular involvement.