title: Topotecan, Ara-C, cisplatin and prednisolone (TOPOSHAP) for patients with refractory and relapsing lymphomas: results of a phase I trial.
abstract: We designed a phase I trial to assess the feasibility of the combination of topotecan, Ara-C, cisplatin and solumedrol (TOPOSHAP) in patients with relapsed or primary refractory lymphomas. We included 9 patients with measurable non-Hodgkin's (n = 8) and Hodgkin's (n = 1) lymphomas. Level 1 consisted of topotecan 1.0 mg/m(2)/day, i.v., given on days 1-3, cisplatin 25 mg/m(2)/day, i.v., on days 1-3, Ara-C 500 mg/m(2), i.v., on day 4, methylprednisolone 250 mg, i.v., on days 1-4. The regimen was repeated every 3-4 weeks. The maximum tolerated dose was already reached at level 1. G-CSF was added systematically after the 5th patient was included. The most significant toxicity in this trial was hematologic (all had neutropenia WHO grade 4 and 7 had grade 4 thrombocytopenia). Three patients had neutropenic fever. We observed two instances of WHO grade 3 and one of grade 4 diarrhea. Two patients achieved a complete response and 6 a partial response. We conclude that TOPOSHAP with G-CSF support is feasible and should be further studied in phase II studies.
authors.affiliation: Hematology-Oncology Division, ABC Foundation School of Medicine, São Paulo, Brazil.
authors.forename: Fernando
authors.initials: F
authors.lastname: Coutinho
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Manhani
authors.forename: William S
authors.initials: WS
authors.lastname: Velasquez
authors.forename: Auro
authors.initials: A
authors.lastname: Del Giglio
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects; D006689:Hodgkin Disease / Q000188:drug therapy*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage* / Q000009:adverse effects; D012008:Recurrence; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D005938:Glucocorticoids; D003561:Cytarabine; D019772:Topotecan; D011239:Prednisolone; D002945:Cisplatin