Objective:It remains unclear whether simultaneous use of two chemotherapeutic drugs is better than sequential use.This trial was designed to explore efficacy and safety of sequential vs simultaneous use of vinorelbine...Objective:It remains unclear whether simultaneous use of two chemotherapeutic drugs is better than sequential use.This trial was designed to explore efficacy and safety of sequential vs simultaneous use of vinorelbine and capecitabine at the same dosage as first-line therapy in metastatic breast cancer (MBC).Methods:This was a un-icenter, randomized phase II trial.Patients randomized into the simultaneous group (group A) were simultaneously administered with vinorelbine and capecitabine while those in the sequential group (group B) received vinorelbine followed by capecitabine at the same dosage.Results:Sixty-six patients were screened and 30 patients were randomized into either group.There're significant differences in the clinical benefit rate (CBR) with 80.0% for group A vs 53.3% for group B (P=0.028).With a median follow up time of 13.5 months, there were no significant differences between the two groups in PFS (median PFS:7.70 months for group A vs 7.23 months for group B, P=0.436).Grade III or IV neutropenia (83.3% vs 50.0%, P=0.006), all grades of fatigue (56.7% vs 30.0%, P=0.037) and anorexia (53.3% vs 23.3%, P=0.017) were significantly more frequent in simultaneous group.Conclusion:Simultaneous administration of vinorelbine and capecitabine can bring about improvements in CBR, but cannot translate into long-term benefits, such as progression-free survival (PFS) or overall survival (OS).These findings, combined with a relatively better tolerability in sequential group, showed that both simultaneous and sequential administrations are reasonable options for MBC patients.展开更多
Since nucleic acids(DNA and RNA) play very important roles in cells,they are molecular targets of many clinically used drugs,such as anticancer drugs and antibiotics.Because of clinical demands for treating various de...Since nucleic acids(DNA and RNA) play very important roles in cells,they are molecular targets of many clinically used drugs,such as anticancer drugs and antibiotics.Because of clinical demands for treating various deadly cancers and drug-resistant strains of pathogens,there are urgent needs to develop novel therapeutic agents.Targeting nucleic acids hasn’t been the mainstream of drug discovery in the past,and the lack of 3D structural information for designing and developing drug specificity is one of the main reasons.Fortunately,many important structures of nucleic acids and their protein complexes have been determined over the past decade,which provide novel platforms for future drug design and discovery.In this review,we describe some useful nucleic acid structures,particularly their interactions with the ligands and therapeutic candidates or even drugs.We summarize important information for designing novel potent drugs and for targeting nucleic acids and protein-nucleic acid complexes to treat cancers and overcome the drug-resistant problems.展开更多
文摘Objective:It remains unclear whether simultaneous use of two chemotherapeutic drugs is better than sequential use.This trial was designed to explore efficacy and safety of sequential vs simultaneous use of vinorelbine and capecitabine at the same dosage as first-line therapy in metastatic breast cancer (MBC).Methods:This was a un-icenter, randomized phase II trial.Patients randomized into the simultaneous group (group A) were simultaneously administered with vinorelbine and capecitabine while those in the sequential group (group B) received vinorelbine followed by capecitabine at the same dosage.Results:Sixty-six patients were screened and 30 patients were randomized into either group.There're significant differences in the clinical benefit rate (CBR) with 80.0% for group A vs 53.3% for group B (P=0.028).With a median follow up time of 13.5 months, there were no significant differences between the two groups in PFS (median PFS:7.70 months for group A vs 7.23 months for group B, P=0.436).Grade III or IV neutropenia (83.3% vs 50.0%, P=0.006), all grades of fatigue (56.7% vs 30.0%, P=0.037) and anorexia (53.3% vs 23.3%, P=0.017) were significantly more frequent in simultaneous group.Conclusion:Simultaneous administration of vinorelbine and capecitabine can bring about improvements in CBR, but cannot translate into long-term benefits, such as progression-free survival (PFS) or overall survival (OS).These findings, combined with a relatively better tolerability in sequential group, showed that both simultaneous and sequential administrations are reasonable options for MBC patients.
基金financially supported by the Georgia Cancer Coalition(GCC) Distinguished Cancer Clinicians and Scientists and by the US National Science Foundation(NSF MCB-0824837)
文摘Since nucleic acids(DNA and RNA) play very important roles in cells,they are molecular targets of many clinically used drugs,such as anticancer drugs and antibiotics.Because of clinical demands for treating various deadly cancers and drug-resistant strains of pathogens,there are urgent needs to develop novel therapeutic agents.Targeting nucleic acids hasn’t been the mainstream of drug discovery in the past,and the lack of 3D structural information for designing and developing drug specificity is one of the main reasons.Fortunately,many important structures of nucleic acids and their protein complexes have been determined over the past decade,which provide novel platforms for future drug design and discovery.In this review,we describe some useful nucleic acid structures,particularly their interactions with the ligands and therapeutic candidates or even drugs.We summarize important information for designing novel potent drugs and for targeting nucleic acids and protein-nucleic acid complexes to treat cancers and overcome the drug-resistant problems.
