To determine the feasibility of neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by concurrent chemoradiotherapy (CHT-RT) compared with the same CHT-RT regimen alone in locally ...advanced head-and-neck squamous cell carcinoma.
We treated 24 patients (20 men and 4 women) who had Stage III-IVM0 squamous cell carcinoma of the oral cavity, oropharynx, nasopharynx, or hypopharynx. The median patient age was 59 years (range, 41–73 years). The stage distribution was as follows: Stage II, 1 patient; Stage III, 6 patients; and Stage IV, 17; 18 patients had a performance status of 0 and 6 had a performance status of 1. None had undergone previous CHT or RT. Group 1 underwent three cycles of CHT (carboplatin area under the curve 1.5 on Days 1–4 and 5-fluorouracil 600 mg/m
2/d continuous infusion for 96 h) starting on Days 1, 22, and 43 during RT (one daily fraction, 66–70 Gy within 33–35 fractions). Group 2 underwent three cycles of neoadjuvant TPF (docetaxel 75 mg/m
2, cisplatin 80 mg/m
2, 5-fluorouracil 800 mg/m
2/d continuous infusion for 96 h) followed by the same CHT-RT regimen.
After the first 16 patients, 8 in Group 1 and 8 in Group 2, the concomitant CHT-RT schedule was modified. The limiting toxicity observed during concomitant CHT-RT was similar in Groups 1 and 2, independent of neoadjuvant TPF administration. An excess of G3-G4 mucositis and other relevant toxicity that did not allowing completion of CHT-RT without interruption occurred in 44% of the patients. A reduction of at least one cycle of concurrent CHT was required in 31% of patients. On the basis of these data, the next 8 patients (Group 3) received three cycles of neoadjuvant TPF followed by two cycles only of CHT (cisplatin 20 mg/m
2 on Days 1–4 and 5-fluorouracil 800 mg/m
2/d continuous infusion for 96 h) (PF) during Weeks 1 and 6 of the planned 7 weeks of RT. In Group 3, 25% of the patients developed World Health Organization G3-G4 mucositis. No World Health Organization hematologic G3-G4 toxicity was seen. RT interruption was required for 2 patients (25%). In 1 patient (12%), one cycle of CHT was omitted. During neoadjuvant TPF (Groups 2 and 3), the principal toxicities were G3-G4 neutropenia (37.5%) and G2 mucositis (44%). At the end of therapy, the CR rate was 62.5% for CHT-RT alone (Group 1) and 80% for neoadjuvant TPF followed by CHT-RT (Groups 2 and 3).
Three cycles of neoadjuvant TPF followed by two cycles of PF during RT are feasible without limiting toxicity. Three cycles of TPF were well tolerated and did not compromise subsequent concomitant CHT-RT. A randomized multicenter Phase III study has been started with the aim of comparing two cycles of PF during RT as standard treatment vs. the experimental arm with three cycles of neoadjuvant TPF followed by two cycles of PF during RT.
An increasing prevalence of antiretroviral therapy (ART) resistance in ART-experienced and ART-naive pregnant women has been reported. Some studies suggest that antiretroviral drug-resistant viruses ...might have decreased replication capacity and transmissibility. However, cases of perinatal transmission of multidrug-resistant HIV type-1 (HIV-1) have been described. Here, we report the case of one child with vertically-acquired multidrug-resistant HIV-1 and the outcome of a rescue therapy with a darunavir/ritonavir- and etravirine-containing antiretroviral regimen. During the 15 months of therapy, the child showed clinical improvement, including no side effects, persistent suppression of viral replication and a great increase in CD4+ T-cell count. Paediatric HIV specialists should be prepared to manage a small, but increasing, number of babies with a 'nightmare' multidrug-resistant virus with no available treatment options. The use of experimental agents might become a compelling issue in vertically HIV-infected children born in the era of highly active ART.
Há evidências de que a terapia com o laser pode estimular a regeneração de nervos e esta hipótese foi testada em ratos. Uma lesão por esmagamento controlado foi produzida no nervo isquiático de 20 ...ratos Wistar, metade dos quais foram submetidos a irradiação efetiva com o laser de arseneto de gálio (AsGa) e a outra metade a irradiação simulada, durante dez dias consecutivos, começando no primeiro dia pós-operatório. Os resultados foram avaliados com três semanas pela medida do índice funcional do isquiático (IFC) em intervalos semanais e pela medida do número total de fibras nervosas e da densidade de fibras dos nervos, após o sacrifício dos animais na terceira semana, com o nível de significância de 5% (p<0.05). Observou-se melhora progressiva do IFC tanto nos nervos irradiados como nos controles (69% e 45%, respectivamente), com diferença significante entre ambos na segunda semana (p=0,04). A densidade de fibras aumentou para os nervos irradiados e diminuiu para os nervos controle, a diferença entre ambos sendo significante (p=0,001). Os autores concluem que a terapia com o laser de baixa intensidade efetivamente acelera a regeneração do nervo isquiático do rato.There are evidences that laser therapy may stimulate nerve regeneration and this hypothesis was tested in rats. A controlled crush injury was produced on the sciatic nerve of 20 Wistar rats, half of which submitted to effective Ga-As laser irradiation and the other half to simulated irradiation for 10 consecutive days beginning on the first postoperative day. Results were evaluated at three weeks postoperatively by measuring the sciatic functional index (SFI) at weekly intervals and the total number of nerve fibers and nerve fiber density of the sciatic nerve at three weeks (p<0.05). The SFI progressively improved for both irradiated and control nerves (69% and 45%, respectively) with a significant difference between them at two weeks (p=0.04). Nerve fiber density increased for the irradiated nerves and decreased for the control nerves, with significant differences between them (p=0.001). Low intensity therapeutic ultrasound accelerates nerve regeneration, as demonstrated with significance on the 21st postoperative day.
Since 1983 we have studied the relationship, in the same patient, between receptor status in breast carcinoma and in nonmalignant breast tissue. Fifty patients have been evaluated to date. The total ...unoccupied cytosol estrogen and progesterone receptors were determined by a dextran-coated charcoal method. In nonmalignant breast tissue we found a measurable receptor concentration above the sensitivity of the method in 62% of cases for estrogen receptors and in 44% of cases for progesterone receptors. No relationships were found between the receptor level of each tumor and that of the corresponding benign tissue. The data suggest that the levels of the receptors in the tumor and in the nonmalignant tissue are totally independent.
Pyridine‐based dendrons (up to the third generation) having an OH group at the focal point react with CO and propyne in the presence of a palladium catalyst to give the corresponding methacrylic ...esters in high yield. The new methacrylic monomers have been homopolymerized with a free radical initiator. While the polymerization of G1‐ and G‐2‐methacrylic esters give high molecular weight polymers, the G‐3‐methacrylic ester affords only oligomeric products.
Há evidências de que a terapia com o laser pode estimular a regeneração de nervos e esta hipótese foi testada em ratos. Uma lesão por esmagamento controlado foi produzida no nervo isquiático de 20 ...ratos Wistar, metade dos quais foram submetidos a irradiação efetiva com o laser de arseneto de gálio (AsGa) e a outra metade a irradiação simulada, durante dez dias consecutivos, começando no primeiro dia pós-operatório. Os resultados foram avaliados com três semanas pela medida do índice funcional do isquiático (IFC) em intervalos semanais e pela medida do número total de fibras nervosas e da densidade de fibras dos nervos, após o sacrifício dos animais na terceira semana, com o nível de significância de 5% (p<0.05). Observou-se melhora progressiva do IFC tanto nos nervos irradiados como nos controles (69% e 45%, respectivamente), com diferença significante entre ambos na segunda semana (p=0,04). A densidade de fibras aumentou para os nervos irradiados e diminuiu para os nervos controle, a diferença entre ambos sendo significante (p=0,001). Os autores concluem que a terapia com o laser de baixa intensidade efetivamente acelera a regeneração do nervo isquiático do rato.
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