The addition of granulocyte-colony stimulating factor shifts the dose limiting toxicity and markedly increases the maximum tolerated dose and activity of the kinesin spindle protein inhibitor SB-743921 in patients with relapsed or refractory lymphoma: Results of an international, multicenter phase I/II study Journal Article
| Authors: | O'Connor, O. A.; Gerecitano, J.; Van Deventer, H.; Hainsworth, J.; Zullo, K. M.; Saikali, K.; Seroogy, J.; Wolff, A.; Escandón, R. |
| Article Title: | The addition of granulocyte-colony stimulating factor shifts the dose limiting toxicity and markedly increases the maximum tolerated dose and activity of the kinesin spindle protein inhibitor SB-743921 in patients with relapsed or refractory lymphoma: Results of an international, multicenter phase I/II study |
| Abstract: | This was a phase I study of SB-743921 (SB-921) in patients with relapsed/refractory lymphoma. Previous studies established that neutropenia was the only dose limiting toxicity (DLT). The primary objective was to determine the DLT, maximum tolerated dose (MTD) and efficacy of SB-921 with and without granulocyte-colony stimulating factor (G-CSF). Sixty-eight patients were enrolled, 42 without G-CSF, 26 with G-CSF. In the cohort without G-CSF, SB-921 doses ranged from 2 to 7 mg/m2, with 6 mg/m2 being the MTD. In the cohort with G-CSF support, doses of 6-10 mg/m2 were administered, with 9 mg/m2 being the MTD, representing a 50% increase in dose density. Fifty-six patients were evaluable for efficacy. Four of 55 patients experienced a partial response (three in Hodgkin lymphoma and one in non-Hodgkin lymphoma, all at doses ≥ 6 mg/m2); 19 patients experienced stable disease, 33 patients developed progression of disease. G-CSF shifted the DLT from neutropenia to thrombocytopenia, allowing for a 50% increase in dose density. Responses were seen at higher doses with G-CSF support. © 2015 Informa UK, Ltd. |
| Keywords: | adult; major clinical study; prednisone; fatigue; doxorubicin; cancer combination chemotherapy; diarrhea; treatment duration; thrombocytopenia; cyclophosphamide; vincristine; vinblastine; hodgkin disease; coughing; drug fever; dyspnea; febrile neutropenia; nonhodgkin lymphoma; algorithm; bone marrow biopsy; lymphoma; bleomycin; mitosis spindle; maximum tolerated dose; phase 1 clinical trial; recombinant granulocyte colony stimulating factor; microtubule; kinesin spindle protein inhibitor; kinesin; hodgkin lymphoma; non-hodgkin lymphoma; chemotherapy induced nausea and vomiting; chemotherapy induced anemia; human; male; female; priority journal; article; patient history of chemotherapy; sb-743921; n (3 aminopropyl) n [1 (3 benzyl 7 chloro 4 oxo 4h chromen 2 yl) 2 methylpropyl] 4 methylbenzamide |
| Journal Title: | Leukemia and Lymphoma |
| Volume: | 56 |
| Issue: | 9 |
| ISSN: | 1042-8194 |
| Publisher: | Taylor & Francis Group |
| Date Published: | 2015-09-01 |
| Start Page: | 2585 |
| End Page: | 2591 |
| Language: | English |
| DOI: | 10.3109/10428194.2015.1004167 |
| PROVIDER: | scopus |
| PUBMED: | 25665464 |
| DOI/URL: | |
| Notes: | Export Date: 2 December 2015 -- Source: Scopus |
