Induction cetuximab, paclitaxel, and carboplatin followed by chemoradiation with cetuximab, paclitaxel, and carboplatin for stage III/IV head and neck squamous cancer: a phase II ECOG-ACRIN trial (E2303).

BACKGROUND: E2303 evaluated cetuximab, paclitaxel, and carboplatin used as induction therapy and concomitant with radiation therapy in patients with stage III/IV head and neck squamous cell carcinoma (HNSCC) determining pathologic complete response (CR), event-free survival (EFS), and toxicity. PATIENTS AND METHODS: Patients with resectable stage III/IV HNSCC underwent induction therapy with planned primary site restaging biopsies (at week 8 in clinical complete responders and at week 14 if disease persisted). Chemoradiation (CRT) began week 9. If week 14 biopsy was negative, patients completed CRT (68-72 Gy); otherwise, resection was carried out. p16 protein expression status was correlated with response/survival. RESULTS: Seventy-four patients were enrolled; 63 were eligible. Forty-four (70%) were free of surgery to the primary site, progression, and death 1-year post-treatment. Following induction, 41 (23 CR) underwent week 8 primary site biopsy and 24 (59%) had no tumor (pathologic CR). Week 14 biopsy during chemoradiation (50 Gy) in 34 (15 previously positive biopsy; 19 no prior biopsy) was negative in 33. Thus 90% of eligible patients completed CRT. Overall survival and EFS were 78% and 55% at 3 years, respectively. Disease progression in 23 patients (37%) was local only in 10 (16%), regional in 5 (8%), local and regional in 2 (3%), and distant in 5 patients (8%). There were no treatment-related deaths. Toxicity was primarily hematologic or radiation-related. p16 AQUA score was not associated with response/survival. CONCLUSIONS: Induction cetuximab, paclitaxel, and carboplatin followed by the same drug CRT is safe and induces high primary site response and promising survival. CLINICAL TRIALS NUMBER: NCT 00089297.

Energy balance in asymptomatic HIV infection.

OBJECTIVES: Body weight is regulated by the balance between energy intake and energy expenditure, but the influence of HIV infection on energy balance has not been fully examined. The main objectives of this study were (1) to assess the effect of HIV on energy balance, (2) to examine the relationship of parameters of immunodeficiency to energy balance, and (3) to examine the interrelationship of different components of energy balance in asymptomatic HIV-seropositive men. DESIGN: A cross-sectional study of nutrition and metabolism in asymptomatic HIV-seropositive men METHODS: Components of energy balance were examined in 104 asymptomatic HIV-seropositive men (CD4 count 4-482 x 10(6)/l) and 57 age-matched HIV-seronegative male controls. Energy and protein intake were measured using 5-day diaries, and small bowel absorption and permeability was assessed using four sugar probes. Resting energy expenditure was calculated from indirect calorimetry and nitrogen loss estimated from 24 h urine collection. Four methods were used to assess the effect of HIV infection on body composition (anthropometry, dual energy X-ray absorptiometry, bioelectrical impedance and 24 h urine creatinine). RESULTS: Resting energy expenditure per kilogram of fat-free mass was raised (P < 0.0001), fat mass was decreased (P = 0.001), fat-free mass was increased (P = 0.05), energy intake was higher (P = 0.05), absorption of L-rhamnose (P = 0.01) and 3-O-methyl-D-glucose was decreased (P = 0.003), and small bowel permeability was increased (P < 0.0001) in HIV-seropositive men compared with HIV-seronegative controls. HIV-seropositive subjects with a CD4 count less than 100 x 10(6)/l had decreased absorption of L-rhamnose (P < 0.05), D-xylose (P < 0.05) and 3-O-methyl-D glucose (P < 0.05) compared with HIV-seropositive subjects at higher CD4 counts, and had a similar resting energy expenditure to HIV-seronegative controls. Protein intake, carbohydrate, fat and protein oxidation. 24 h nitrogen excretion and appendicular muscle mass were similar in HIV-seropositive men and controls. CONCLUSION: HIV infection exerts a direct effect on parameters of energy balance that varies with the severity of immunosuppression.

On the existence of receptors to the pheromonal steroid, 5 alpha-androst-16-en-3-one, in porcine nasal epithelium.

The binding of the odorant, 5 alpha-androst-16-en-3-one, to porcine nasal tissues, has been investigated using methods normally employed for studying both cytosolic and membrane-bound receptors. 5 alpha-Androst-16-en-3-one was generally taken up more avidly by homogenates of olfactory (nervous) tissue than by respiratory tissue, but binding to the former was only partially prevented by prior heating or by excess ligand, suggesting some degree of specific binding. At low protein concentration, saturable binding was noted but these data were not reproducible. The binding of a non-odorant, DHA, was only 2% that of 5 alpha-androst-16-en-3-one. Using agarose gel electrophoresis, some evidence was obtained for binding protein(s) to the odorous 16-adrostene in porcine respiratory tissues, that were absent from previously heated tissue. Experiments with SDS-treated, or cell-membrane-enriched preparations, of nasal epithelium did not show improved binding of 5 alpha-androst-16-en-3-one. We conclude that the extreme hydrophobicity of 5 alpha-androst-16-en-3-one is probably responsible for the high degree of non-specific binding noted and for variability in results. This is discussed in relation to other known odorous ligand/receptors in olfactory tissue, particularly that of 5 alpha-androstan-3-one.

Heat treatment for endocrinological investigations on plasma positive for human immunodeficiency virus (HIV).

The effects of heat treatment of serum samples on the hormone analyses used in this laboratory were studied. Total T4, testosterone, progesterone, and growth hormone were not systematically affected by heat treatment over the whole range of analyte concentrations studied; for thyroid stimulating hormone, no effect was noted on serum samples with concentrations of less than 10 mU/l. Significant changes occurred in total T3, cortisol, follicle stimulating hormone, luteinizing hormone, and prolactin. It is suggested that with appropriate preliminary study, heat treated plasma samples may be used in endocrinological investigations without adversely affecting the diagnostic validity of the results.

Biochemical assessment of pancreatic disease in human immunodeficiency virus infected men.

AIM: To determine the usefulness of measuring amylase activity as an indicator of pancreatic disease in human immunodeficiency virus (HIV) positive patients. METHODS: A prospective study of 129 ambulant HIV positive males. Total amylase, pancreatic amylase, and lipase activities were assayed using commercial test kits on an automated analyser. Samples with raised amylase were examined for the presence of macroamylasaemia using cellulose acetate electrophoresis. RESULTS: Thirty six (28%) of the subjects had raised total amylase activities compared with healthy, age matched blood donors. However, almost half of these were because of an increase of the salivary fraction. Four subjects were found to have macroamylasaemia. Pancreatic amylase and lipase assays, more specific indicators of pancreatic disease, produced significantly fewer abnormal results. There was no association between abdominal symptoms and elevated enzyme levels. CONCLUSIONS: Total amylase is a poor indicator of pancreatic disease in HIV infected outpatients. Specific assays for pancreatic amylase offer advantages over the traditional total amylase assay. The lipase assay produced the least number of abnormal results and its use could improve the biochemical identification of patients with possible pancreatic disease and allow a more selective investigation of these cases.

Abnormal indices of nutrition in the elderly: a study of different clinical groups.

Anthropometric and biochemical indices of nutrition were measured in 450 elderly women in six groups spanning a wide range of physical dependency. Data from the group of active subjects living at home was used to derive reference ranges for elderly women. Although the index values of this group did not differ greatly from those seen in young subjects, there were large differences between this and some of the other elderly groups where the frequency of low values was as high as 50% for some parameters. Food intakes were measured in four of the six groups and relationships were found between energy, protein and vitamin C intake and body weight, plasma protein levels and vitamin C concentration, respectively. Our findings suggest that, among elderly women, low levels of nutrient intake make a significant contribution to poor anthropometric and biochemical nutritional status. Improvements in diet should be reflected in the indices measured and might, in turn, have beneficial effects on health.

Nutritional state of elderly women on admission to mental hospital.

Since nutritional deficiencies might worsen the severity of symptoms and prolong the length of illness in non-nutritional disorders, particularly in the elderly, we examined the nutritional status of 216 elderly women newly admitted to a mental hospital. Compared to healthy elderly women, they had lower values for plasma prealbumin, vitamin C, and B vitamins. This was particularly common in senile dementia, and appeared to be the result of inadequate intake of protein or vitamins. Regular hospital diet for one month corrected the very low levels of prealbumin, but supplements were essential to remove deficiency of the water-soluble vitamins. Although vitamin supplements did not influence the length of stay in hospital, we did not exclude the possibility that nutritional deficiencies have a significant effect on the severity of mental illness.