A randomized phase 2 trial of a preparative regimen of bortezomib, high-dose melphalan, arsenic trioxide, and ascorbic acid Journal Article
| Authors: | Sharma, M.; Khan, H.; Thall, P. F.; Orlowski, R. Z.; Bassett, R. L. Jr; Shah, N.; Bashir, Q.; Parmar, S.; Wang, M.; Shah, J. J.; Hosing, C. M.; Popat, U. R.; Giralt, S. A.; Champlin, R. E.; Qazilbash, M. H. |
| Article Title: | A randomized phase 2 trial of a preparative regimen of bortezomib, high-dose melphalan, arsenic trioxide, and ascorbic acid |
| Abstract: | BACKGROUND: Bortezomib is active for newly diagnosed and relapsed multiple myeloma, and it has synergistic activity with melphalan. The authors of this report conducted a randomized trial to determine the safety and efficacy of adding bortezomib to a preparative regimen of arsenic trioxide (ATO), ascorbic acid (AA), and melphalan. METHODS: Among 60 patients who enrolled between October 2006 and September 2007, 58 patients underwent autologous transplantation with a preparative regimen of melphalan 200 mg/m 2 intravenously, AA 1000 mg daily intravenously for 7 days, and ATO 0.25 mg/kg intravenously for 7 days. Patients were randomized to receive no bortezomib (Group 1), bortezomib 1 mg/m 2 × 3 doses (Group 2), and bortezomib 1.5 mg/m 2 × 3 doses (Group 3). Primary endpoints were complete response (CR), grade IV toxicity, and 90-day treatment-related mortality (TRM). Secondary endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: The median follow-up of all surviving patients was 36 months (range, 20-43 months). The CR rates in Groups 1, 2, and 3 were 20%, 10%, and 10%, respectively. Grade 3 and 4 nonhematologic toxicities and TRM were comparable. The median OS was not reached in the groups, whereas the median PFS in Groups 1, 2, and 3 was 17.8 months, 17.4 months, and 20.7 months, respectively. PFS and OS were significantly shorter in patients who had high-risk cytogenetics (P =.016 and P =.0001, respectively) and relapsed disease (P =.0001 and P =.0001, respectively) regardless of the treatment group. CONCLUSIONS: Adding bortezomib to a preparative regimen of ATO, AA, and high-dose melphalan was safe and well tolerated in patients with multiple myeloma. There was no significant improvement in the CR rate, PFS, or OS in the bortezomib groups. Copyright © 2011 American Cancer Society. |
| Keywords: | adult; cancer survival; controlled study; treatment response; aged; major clinical study; overall survival; lenalidomide; thalidomide; neutropenia; salvage therapy; doxorubicin; cancer combination chemotherapy; diarrhea; drug efficacy; drug safety; heart left ventricle failure; hypertension; monotherapy; side effect; treatment duration; treatment planning; drug megadose; progression free survival; bortezomib; infection; multiple cycle treatment; multiple myeloma; neutrophil count; heart disease; lung disease; mucosa inflammation; nausea; maintenance therapy; aciclovir; cyclophosphamide; dexamethasone; hemoglobin; melphalan; vincristine; deep vein thrombosis; cancer mortality; dyspnea; febrile neutropenia; pneumonia; arsenic trioxide; acute kidney failure; cause of death; hypotension; blood; engraftment; thorax pain; vein thrombosis; stem cell mobilization; thrombocyte count; sepsis; cancer relapse; pleura effusion; ascorbic acid; intestine obstruction; levofloxacin; granulocyte colony stimulating factor; gastrointestinal disease; fluconazole; tachycardia; myeloma; multiple organ failure; fluid retention; weight gain; autologous transplantation; autotransplantation; lung edema |
| Journal Title: | Cancer |
| Volume: | 118 |
| Issue: | 9 |
| ISSN: | 0008-543X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2012-05-01 |
| Start Page: | 2507 |
| End Page: | 2515 |
| Language: | English |
| DOI: | 10.1002/cncr.26517 |
| PROVIDER: | scopus |
| PUBMED: | 21887685 |
| PMCID: | PMC4015116 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 4 June 2012" - "CODEN: CANCA" - "Source: Scopus" |
