title: Phase I trial examining addition of gemcitabine to CHOP in intermediate grade NHL.
abstract: OBJECTIVE
  Gemcitabine induces a 20% response as single-agent therapy in patients with relapsed or refractory NHL. We report phase I findings of gemcitabine in combination with standard CHOP chemotherapy with G-CSF support for intermediate grade NHL. The protocol was modified during enrollment to include rituximab in CD 20+ lymphomas.
  
  
  METHODS
  Patients received CHOP plus gemcitabine at 500 mg/m(2) (Cohort 1) or 750 mg/m(2) (Cohort 2) on days 1 and 4 of each 21-day cycle. Accrual was suspended once each cohort was filled. Dose escalation occurred after all patients in the cohort were determined to not have a dose-limiting toxicity.
  
  
  RESULTS
  Between April 2002 and May 2004, 10 patients were enrolled and completed the study treatment (6 in Cohort 1, 4 in Cohort 2). In Cohort 1, grade 3 toxicities included neutropenia, anemia, neuropathy, and constipation. Grade 4 toxicities were febrile neutropenia and thrombocytopenia. In Cohort 2, grade 3 toxicities included neutropenia, thrombocytopenia, mucositis, anemia, and intestinal obstruction. Grade 4 toxicities included febrile neutropenia, neutropenia, and thrombocytopenia. One patient developed MDS 36 months after chemotherapy. Three of four patients in Cohort 2 developed dose-limiting toxicities (mucositis and thrombocytopenia) requiring dose reduction in gemcitabine after cycle 1. Overall, the survival rate at 2.5 years was 71%.
  
  
  CONCLUSIONS
  This Phase I trial concludes that gemcitabine 500 mg/m(2) on days 1 and 4 of each 21-day cycle is the maximum tolerated dose when combined with standard CHOP chemotherapy with G-CSF support for intermediate grade NHL.
authors.affiliation: Department of Hematology/Oncology, The Miriam Hospital, 164 Summit Avenue, Providence, RI 02906, USA. jreagan@lifespan.org
authors.forename: John L
authors.initials: JL
authors.lastname: Reagan
authors.forename: Alan
authors.initials: A
authors.lastname: Rosmarin
authors.forename: James N
authors.initials: JN
authors.lastname: Butera
authors.forename: Ahmed
authors.initials: A
authors.lastname: Nadeem
authors.forename: Fred J
authors.initials: FJ
authors.lastname: Schiffman
authors.forename: William M
authors.initials: WM
authors.lastname: Sikov
authors.forename: Eric
authors.initials: E
authors.lastname: Winer
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Mega
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D018951:Antigens, CD20 / Q000276:immunology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000069283:Rituximab; D015996:Survival Rate; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000093542:Gemcitabine
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D003841:Deoxycytidine; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone; D000093542:Gemcitabine