The intravenous administration of various fat emulsions to dogs has been studied in this laboratory (1). Of the emulsions used, one consisting of 15 per cent refined coconut oil stabilized with a purified preparation of soybean phosphatides was found to be well tolerated, and produced only minor pathologic effects after daily infusions for periods of 1 month. In these experiments, amounts of the emulsified fat were used sufficient to give 15 or 16 calories per kgm. of body weight per day. The use of such an emulsion for nutritive purposes would depend on whether or not fat administered in this manner can be efficiently utilized as a source of energy. A study of this problem forms the basis of the present paper.The utilization of fat given intravenously has been studied by several investigators. Nomura (2) found no decrease in the respiratory quotient of dogs following the infusion of an olive oil-cod liver oil emulsion stabilized with egg phosphatides. This was also found in dogs which had fasted 4 to 8 days previous to the infusion, although the initial respiratory quotients were much lower in this series. Baba (3) fed dogs a meat diet with thyroxiti to produce energy deficiency and weight loss. Infusion of this same olive oil-cod liver oil emulsion produced slight decreases in the non-protein respiratory quotient of the magnitude of from 0. lard emulsion into dogs. Gordon and Levine (6) observed decreases in the respiratory quotient of from 0.03 to 0.07 following infusion of an olive oil emulsion stabilized with egg phosphatides in a healthy infant, starting with initial respiratory quotients between 0.9 and 1.0. At a control respiratory quotient of 0.8, no significant lowering was produced by infusions of the fat emulsion. No decreases in the respiratory quotient were obtained after infusion of this emulsion into a marasmic infant. In general, it may be concluded that these studies on the effect of intravenous fat emulsions on the respiratory quotient indicate that the fat is utilized, but the evidence is equivocal since the changes are small. It is unfortunate that the respiratory quotient of starvation approaches that of fat metabolism, and thus reduces the value of this criterion of utilization under the conditions in which it is desirable to use fat intravenously: namely, in serious energy deficiency. More definite evidence of utilization should be obtained by other methods of study. Narat (7) studied starvation survival in 2 pairs of dogs, 1 of each pair receiving by infusion a small amount of an olive oil emulsion stabilized with egg phosphatides. The control dogs died on the 36th and 31st day of starvation, while those receiving the fat infusions survived through the 46th and 45th day respectively. Weight losses were slightly less in the infused dogs. The author concluded from these differences that the fat was utilized. Dunham and Brunschwig (8)

No abstract

ObjectiveFor most patients suffering from recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC), chemotherapy is the main option after considering surgery and reirradiation. Cetuximab combined with a platinum-fluorouracil regimen (EXTREME) has been the standard of care for over a decade. Nevertheless, a significant number of patients remain unfit for this regimen because of age, severe comorbidities, or poor performance status. The aim of this study is to investigate an alternative regimen with sufficient efficacy and safety.MethodsWe reviewed retrospectively the medical charts of all patients treated with paclitaxel, carboplatin, and cetuximab (PCC) at our institution. Eligibility criteria were as follows: first-line R/M-HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx not suitable for local therapy, cisplatin, and/or 5-FU ineligibility, ECOG-PS: 0–2. PCC consisted of paclitaxel 80 mg/m2, carboplatin AUC 2, and cetuximab at an initial dose of 400 mg/m2 then 250 mg/m2, for 16 weekly administrations followed by cetuximab maintenance for patients for whom a disease control was obtained. The primary endpoint was overall survival (OS), and secondary endpoints were overall response rate (ORR), progression free survival (PFS), and safety.ResultsWe identified 60 consecutive patients treated with PCC between 2010 and 2016 at our institution. Thirty-one patients (52%) were ECOG-PS 2. Fifty-five patients (92%) were cisplatin ineligible. ORR was 43.3% (95% CI, 30.8–55.8), and disease control rate was 65% (95% CI, 52.9–77.1). With a median follow-up of 35.7 months (IQR 28.6–48.8), median PFS was 5.8 months (95% CI, 4.5–7.2), and median OS was 11.7 months (95% CI, 7.5-14.8). For ECOG-PS 0–1 patients, median OS was 14.8 months (95% CI, 12.2–21.7) while it was only 7.5 months (95%CI: 5.5-12.7) for ECOG-PS 2 patients (p < 0.04). Grades III–IV toxicities occurred in 30 patients (50%). Most toxicities were hematologic. Six patients (10%) had febrile neutropenia. Nonhematologic toxicities were reported such as cutaneous toxicities, neuropathy, infusion-related reactions, or electrolyte disorders.ConclusionThe weekly PCC regimen seems to be an interesting option in cisplatin-unfit patients. This study shows favorable PFS and OS when compared with what is achieved with the EXTREME regimen and a high controlled disease rate with predictable and manageable toxicities even in the more fragile population.

No abstract

No abstract