title: A phase I/II trial of pixantrone (BBR2778), methylprednisolone, cisplatin, and cytosine arabinoside (PSHAP) in relapsed/refractory aggressive non-Hodgkin's lymphoma.
abstract: The purpose of the study was to evaluate the safety, efficacy, and pharmacokinetics of pixantrone (BBR2778) when substituted for etoposide in the ESHAP regimen in patients with aggressive relapsed or refractory non-Hodgkin's lymphoma. Nineteen patients received protocol therapy, consisting of pixantrone 80 mg/m2 over 1 h on day 1, methylprednisolone 500 mg on days 1 - 5, cisplatin 25 mg/m2 on days 1 - 4, and cytarabine 2000 mg/m2 on day 5. Cycles were repeated every 21 days, in the outpatient setting. Dose limiting toxicity, consisting of bone marrow suppression, occurred at the first dose level (80 mg/m2), which was defined as the recommended dose. Grade 3 and 4 toxicities were mainly hematologic. Only one patient had grade 4 febrile neutropenia. No significant decreases in ejection fraction greater than 20% occurred. Overall response rate was 58%, with 37% complete and 21% partial responses. Six of the 11 responders (55%) underwent stem cell transplant. Median time to progression and overall median survival were 5.7 months and 14.5 months, respectively. There is no significant interaction between pixantrone and the combined drugs. The recommended dose of pixantrone in combination with methylprednisolone, cytarabine, and cisplatin (PSHAP) is 80 mg/m2. PSHAP is an active salvage regimen and should be further evaluated as a pretransplant cytoreductive regimen.
authors.affiliation: National Cancer Centre, Singapore.
authors.forename: Soon-Thye
authors.initials: ST
authors.lastname: Lim
authors.forename: L
authors.initials: L
authors.lastname: Fayad
authors.forename: A
authors.initials: A
authors.lastname: Tulpule
authors.forename: M
authors.initials: M
authors.lastname: Modiano
authors.forename: F
authors.initials: F
authors.lastname: Cabanillas
authors.forename: B
authors.initials: B
authors.lastname: Laffranchi
authors.forename: C
authors.initials: C
authors.lastname: Allievi
authors.forename: A
authors.initials: A
authors.lastname: Bernareggi
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Levine
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000378:metabolism; D011446:Prospective Studies; D012074:Remission Induction; D016879:Salvage Therapy; D016896:Treatment Outcome
chemical_list: D007546:Isoquinolines; D003561:Cytarabine; C086548:pixantrone; D002945:Cisplatin; D008775:Methylprednisolone