title: [A phase Ⅰ dose-escalating trial of pegylated liposomal doxorubicin in combination with cyclophosphamide, vincristine and prednisone for aggressive non-Hodgkin lymphoma].
abstract: Objective:To explore the maximum tolerated dose of pegylated liposomal doxorubicin (PLD) in combination with cyclophosphamide, vincristine and prednisone as a modified CHOP regimen for aggressive non-Hodgkin lymphoma.Methods:Patients with newly diagnosed aggressive non-Hodgkin lymphoma were eligible for this trial. PLD was administered in cycle 1 and categorized into 4 dose level (30 mg/m2, 35 mg/m2, 40 mg/m2, 45 mg/m2D1) according to a 3 + 3 approach for dose-escalation. Doxorubin was used in cycles 2-6. In this combination regimen, the doses of cyclophosphamide (750 mg/m2D1), vincristine (1.4 mg/m2D1, maximum dose of 2 mg) and prednisone (100 mg D1-5) were fixed. Toxicities of cycle 1 were documented.Results:Totally, 21 patients were enrolled in this trial. Among them, 15 patients had T-cell lymphoma and 6 had B-cell lymphoma. When the dose of PLD was escalated to the level of 45 mg/m2, 2 of 3 patients developed grade 3 mucositis, which met the criteria of dose-limiting toxicity. Therefore, the dose was de-escalated for one level. At the level of 40 mg/m2, only one among 12 patients had pneumonia and grade 4 neutropenia. In all dose levels, the grade 3/4 toxicities observed were neutropenia (13 cases, 61.9% ), mucositis (2 cases, 9.5% ), thrombocytopenia (1 case, 4.8%) and pneumonia (1 case, 4.8%).Conclusion:When combined with cyclophosphamide, vincristine and prednisone as a combination regimen, the maximum tolerated dose of PLD was 40 mg/m2.
authors.affiliation: Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: W N
authors.initials: WN
authors.lastname: Shen
authors.forename: D M
authors.initials: DM
authors.lastname: Ji
authors.forename: K
authors.initials: K
authors.lastname: Xue
authors.forename: Q L
authors.initials: QL
authors.lastname: Zhang
authors.forename: F F
authors.initials: FF
authors.lastname: Lyu
authors.forename: X N
authors.initials: XN
authors.lastname: Hong
authors.forename: J N
authors.initials: JN
authors.lastname: Cao
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell; D008228:Lymphoma, Non-Hodgkin; D016399:Lymphoma, T-Cell; D008297:Male; D008875:Middle Aged; D009503:Neutropenia; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011239:Prednisolone / Q000008:administration & dosage; D011241:Prednisone; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone; D011241:Prednisone