Fotemustine-based therapy in combination with rituximab as a first-line induction chemotherapy followed by WBRT for newly diagnosed primary central nervous system lymphoma: a prospective phase II trial

Objective:This study aimed to evaluate the safety,efficacy,and feasibility of the rituximab,fotemustine,pemetrexed,and dexamethasone(R-FPD)regimen followed by whole-brain radiotherapy(WBRT)for patients with primary central nervous system lymphoma(PCNSL).Methods:A prospective,single-center phase II clinical trial was conducted.Patients with PCNSL newly diagnosed at the First Affiliated Hospital of Zhengzhou University between July 2018 and July 2020 were studied.The R-FPD regimen consisted of rituximab(375 mg/m2 i.v.on D0),fotemustine(100 mg/m2 i.v.on D1),pemetrexed(600 mg/m2 i.v.on D1),and dexamethasone(40 mg i.v.on D1-5).Patients 60 years or younger who showed a complete response(CR)were treated with 23.4 Gy of WBRT after the end of chemotherapy;those older than 60 years with CR were treated with a wait-and-see approach;and those who did not show CR after the 4th cycle of chemotherapy were given salvage WBRT 30 Gy+local tumor field irradiation up to 45 Gy,regardless of age.Results:A total of 30 patients were included.After 2 cycles,the objective response rate(ORR)was 96.5%(28/29,1 CR,27 PR,0 SD,and 1 PD).After 4 cycles,the ORR was 73.1%(19/26,11 CR,8 PR,4 SD,and 3 PD).After WBRT,the ORR was 90.9%(10/11,7 CR,3 PR,and 1 SD).The grade III and IV toxicity responses were mainly leukopenia(20.0%),thrombocytopenia(23.3%),and anemia(10.0%).Conclusions:Fotemustine-based therapy in combination with rituximab chemotherapy followed by WBRT can improve outcomes,providing ORR benefits and favorable tolerability in patients newly diagnosed with PCNSL.

A New Class of Amide Ligands Enable Cu-Catalyzed Coupling of Sodium Methanesulfinate with （Hetero）aryl Chlorides

（（2S,4R）-4-Hydroxy-N-（2-methylnaphthalen-l-yl）pyrrolidine-2-carboxamide （HMNPC）, an amide derived from 4-hydroxy-L-proline and 2-methyl naphthalen-l-amine, is a powerful ligand for Cu-catalyzed coupling of （het- ero）aryl halides with sulfinic acid salts, allowing for first time the metal-catalyzed coupling of （hetero）aryl chlorides and NaSO2Me. A considerable number of （hetero）aryl chlorides worked well, providing the pharmaceutically im- portant （hetero）aryl methylsulfones in good to excellent yields.