AIM:To investigate feasibility,morbidity and surgical mortality of a docetaxel-based chemotherapy regimen randomly administered before or after gastrectomy in patients suffering from locally-advanced resectable gastri...AIM:To investigate feasibility,morbidity and surgical mortality of a docetaxel-based chemotherapy regimen randomly administered before or after gastrectomy in patients suffering from locally-advanced resectable gastric cancer.METHODS:Patients suffering from locally-advanced(T3-4 any N M0 or any T N1-3 M0)gastric carcinoma,staged with endoscopic ultrasound,bone scan,computed tomography,and laparoscopy,were assigned to receive four 21 d/cycles of TCF(docetaxel 75 mg/m 2 day 1,cisplatin 75 mg/m 2 day 1,and fluorouracil 300 mg/m 2 per day for days 1-14),either before(Arm A)or after(Arm B)gastrectomy.Operative morbidity,overall mortality,and severe adverse events were compared by intention-to-treat analysis.RESULTS:From November 1999 to November 2005,70 patients were treated.After preoperative TCF(Arm A),thirty-two(94%)resections were performed,85% of which were R0.Pathological response was complete in 4 patients(11.7%),and partial in 18(55%).No surgical mortality and 28.5%morbidity rate were observed,similar to those of immediate surgery arm(P= 0.86).Serious chemotherapy adverse events tended to be more frequent in arm B(23%vs 11%,P=0.07),with a single death per arm.CONCLUSION:Surgery following docetaxel-based chemotherapy was safe and with similar morbidity to immediate surgery in patients with locally-advanced resectable gastric carcinoma.展开更多
Deregulation of the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)- mammalian target of rapamycin(m TOR) signaling pathway is one of the most commonlyinvolved pathways in tumorigenesis. It has also been reporte...Deregulation of the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)- mammalian target of rapamycin(m TOR) signaling pathway is one of the most commonlyinvolved pathways in tumorigenesis. It has also been reported as altered in neuroendocrine tumors(NETs). m TOR inhibitors used in clinical practice are derived from rapamycin,an anti-cancer agent also used as an immunosuppressor after organ transplantation. Everolimus and temsirolimus are the two rapamycin-derived m TOR inhibitors used in NETs. Notably everolimus has been approved in advanced progressive well/moderatelydifferentiated pancreatic NETs(p NETs). It inhibits specifically the m TORC1 subunit of m TOR,not interacting with m TORC2. Although everolimus produced a significant prolongation of progression-free survival a number of patients with p NETs do not benefit from the drug due to early or late progression. Two supposed mechanisms of resistance to m TOR inhibitors are Akt and PI3 K activation,by means of m TORC2 and insulin growth factor(IGF)- IGF receptor signaling,respectively. BEZ235 is a multi-targeted inhibitor binding to PI3 K,m TORC1 and m TORC2,therefore potentially turning off all the supposed molecular targets of resistance to everolimus. The two clinical trials designed in p NETs were stopped early due to unmet statistical endpoint and the global clinical development of BEZ235 was also halted. Tolerability of this drug was challenging and conditioned the feasibility of therapy. The BEZ experience is an example of the huge difference between the preclinical and clinical setting and prompts us to pay more attention to the phase Ⅰ step of clinical development and the design of phase Ⅱ clinical trials.展开更多
Neuroendocrine neoplasms(NENs) are a group of rare and heterogeneous malignancies, which can develop in various organs. The clinical course of NENs is quite heterogeneous, with different spontaneous growth rates after...Neuroendocrine neoplasms(NENs) are a group of rare and heterogeneous malignancies, which can develop in various organs. The clinical course of NENs is quite heterogeneous, with different spontaneous growth rates after diagnosis, and different degrees of sensitivity to the same therapy even when they have similar characteristics. Watch and wait(W and W), is a term coined to indicate observation being conducted to assess the evolution of the tumor without administering any anti-tumor therapy. It has been applied to NENs since in extremely rare cases they tend to remain stable for a long time. Although W and W has been reported in several guidelines and recommendations it has never been validated, nor has it been specifically investigated. Furthermore it is not standardized. Therefore its application in clinical practice can differ in terms of tumor status assessment, type and timing of imaging or other exams utilized. In conclusion, while undertaking W and W to delay the first-line therapy by some weeks may be justified in good performance asymptomatic patients with low-grade NENs in order to usefully characterize the disease and patient and thereby choose the best therapy and therapeutic strategy, it seems to be far more difficult to justify W and W with the intent of avoiding an anti-tumor treatment. It should be considered that not only do NENs tend to grow even when they have very favorable biological characteristics but also that the alternative to W and W is most commonly a low toxic and effective treatment with somatostatin analogs.展开更多
Pancreatic neuroendocrine tumors(panNETs)represent a rare subgroup of neuroendocrine neoplasms(NENs)which showed an impressive increase of incidence over the last decade(1).As over the same period particularly low sta...Pancreatic neuroendocrine tumors(panNETs)represent a rare subgroup of neuroendocrine neoplasms(NENs)which showed an impressive increase of incidence over the last decade(1).As over the same period particularly low stage and low grade NETs had the highest increase it is plausible that small(e.g.,</=2 cm)panNETs incidentally detected may have had a major role thanks to the progress of imaging.展开更多
文摘AIM:To investigate feasibility,morbidity and surgical mortality of a docetaxel-based chemotherapy regimen randomly administered before or after gastrectomy in patients suffering from locally-advanced resectable gastric cancer.METHODS:Patients suffering from locally-advanced(T3-4 any N M0 or any T N1-3 M0)gastric carcinoma,staged with endoscopic ultrasound,bone scan,computed tomography,and laparoscopy,were assigned to receive four 21 d/cycles of TCF(docetaxel 75 mg/m 2 day 1,cisplatin 75 mg/m 2 day 1,and fluorouracil 300 mg/m 2 per day for days 1-14),either before(Arm A)or after(Arm B)gastrectomy.Operative morbidity,overall mortality,and severe adverse events were compared by intention-to-treat analysis.RESULTS:From November 1999 to November 2005,70 patients were treated.After preoperative TCF(Arm A),thirty-two(94%)resections were performed,85% of which were R0.Pathological response was complete in 4 patients(11.7%),and partial in 18(55%).No surgical mortality and 28.5%morbidity rate were observed,similar to those of immediate surgery arm(P= 0.86).Serious chemotherapy adverse events tended to be more frequent in arm B(23%vs 11%,P=0.07),with a single death per arm.CONCLUSION:Surgery following docetaxel-based chemotherapy was safe and with similar morbidity to immediate surgery in patients with locally-advanced resectable gastric carcinoma.
文摘Deregulation of the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)- mammalian target of rapamycin(m TOR) signaling pathway is one of the most commonlyinvolved pathways in tumorigenesis. It has also been reported as altered in neuroendocrine tumors(NETs). m TOR inhibitors used in clinical practice are derived from rapamycin,an anti-cancer agent also used as an immunosuppressor after organ transplantation. Everolimus and temsirolimus are the two rapamycin-derived m TOR inhibitors used in NETs. Notably everolimus has been approved in advanced progressive well/moderatelydifferentiated pancreatic NETs(p NETs). It inhibits specifically the m TORC1 subunit of m TOR,not interacting with m TORC2. Although everolimus produced a significant prolongation of progression-free survival a number of patients with p NETs do not benefit from the drug due to early or late progression. Two supposed mechanisms of resistance to m TOR inhibitors are Akt and PI3 K activation,by means of m TORC2 and insulin growth factor(IGF)- IGF receptor signaling,respectively. BEZ235 is a multi-targeted inhibitor binding to PI3 K,m TORC1 and m TORC2,therefore potentially turning off all the supposed molecular targets of resistance to everolimus. The two clinical trials designed in p NETs were stopped early due to unmet statistical endpoint and the global clinical development of BEZ235 was also halted. Tolerability of this drug was challenging and conditioned the feasibility of therapy. The BEZ experience is an example of the huge difference between the preclinical and clinical setting and prompts us to pay more attention to the phase Ⅰ step of clinical development and the design of phase Ⅱ clinical trials.
文摘Neuroendocrine neoplasms(NENs) are a group of rare and heterogeneous malignancies, which can develop in various organs. The clinical course of NENs is quite heterogeneous, with different spontaneous growth rates after diagnosis, and different degrees of sensitivity to the same therapy even when they have similar characteristics. Watch and wait(W and W), is a term coined to indicate observation being conducted to assess the evolution of the tumor without administering any anti-tumor therapy. It has been applied to NENs since in extremely rare cases they tend to remain stable for a long time. Although W and W has been reported in several guidelines and recommendations it has never been validated, nor has it been specifically investigated. Furthermore it is not standardized. Therefore its application in clinical practice can differ in terms of tumor status assessment, type and timing of imaging or other exams utilized. In conclusion, while undertaking W and W to delay the first-line therapy by some weeks may be justified in good performance asymptomatic patients with low-grade NENs in order to usefully characterize the disease and patient and thereby choose the best therapy and therapeutic strategy, it seems to be far more difficult to justify W and W with the intent of avoiding an anti-tumor treatment. It should be considered that not only do NENs tend to grow even when they have very favorable biological characteristics but also that the alternative to W and W is most commonly a low toxic and effective treatment with somatostatin analogs.
文摘Pancreatic neuroendocrine tumors(panNETs)represent a rare subgroup of neuroendocrine neoplasms(NENs)which showed an impressive increase of incidence over the last decade(1).As over the same period particularly low stage and low grade NETs had the highest increase it is plausible that small(e.g.,</=2 cm)panNETs incidentally detected may have had a major role thanks to the progress of imaging.
