Yttrium-90 ibritumomab tiuxetan doses calculated to deliver up to 15 Gy to critical organs may be safely combined with high-dose BEAM and autologous transplantation in relapsed or refractory B-cell non-Hodgkin's lymphoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] Journal article | | Title | Yttrium-90 ibritumomab tiuxetan doses calculated to deliver up to 15 Gy to critical organs may be safely combined with high-dose BEAM and autologous transplantation in relapsed or refractory B-cell non-Hodgkin's lymphoma. | | Author(s) | Winter JN, Inwards DJ, Spies S, Wiseman G, Patton D, Erwin W, Rademaker AW, Weitner BB, Williams SF, Tallman MS, Micallef I, Mehta J, Singhal S, Evens AM, Zimmer M, Molina A, White CA, Gordon LI | | Institution | Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. j-winter@northwestern.edu | | Source | J Clin Oncol 2009 Apr 1; 27(10):1653-9. | | MeSH | Adult
Aged
Antibodies, Monoclonal
Antineoplastic Agents
Antineoplastic Combined Chemotherapy Protocols
Bone Marrow Transplantation
Carmustine
Combined Modality Therapy
Cytarabine
Female
Humans
Kaplan-Meiers Estimate
Lymphoma, B-Cell
Male
Maximum Tolerated Dose
Melphalan
Middle Aged
Neoplasm Recurrence, Local
Podophyllotoxin
Radioimmunotherapy
Radiotherapy Dosage
Salvage Therapy
Transplantation, Autologous
| | Abstract | PURPOSE: To determine the maximum-tolerated radiation-absorbed dose (RAD) to critical organs delivered by yttrium-90 ((90)Y) ibritumomab tiuxetan in combination with high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy with autologous transplantation.
PATIENTS AND METHODS: Eligible patients had relapsed or refractory CD20+ non-Hodgkin's lymphoma (NHL). Individualized (90)Y activities were based on dosimetry and were calculated to deliver cohort-defined RAD (1 to 17 Gy) to critical organs with three to six patients per cohort. The therapeutic dose of (90)Y ibritumomab tiuxetan was followed by high-dose BEAM and autologous transplantation.
RESULTS: Forty-four patients were treated. Thirty percent of patients had achieved less than a partial remission to their most recent therapy and would not have been eligible for autologous transplantation at most centers. The toxicity profile was similar to that associated with high-dose BEAM chemotherapy. Two dose-limiting toxicities occurred at the 17 Gy dose level, which made 15 Gy the recommended maximum-tolerated RAD. Although eight patients received at least twice the conventional dose of 0.4 mCi/kg, a weight-based strategy at 0.8 mCi/kg would have resulted in a wide range of RAD; nearly 25% of patient cases would have received 17 Gy or more, and many would have received less than 10 Gy. With a median follow-up of 33 months for all patients, the estimated 3-year progression-free and overall survivals were 43% and 60%, respectively.
CONCLUSION: Dose-escalated (90)Y ibritumomab tiuxetan may be safely combined with high-dose BEAM with autologous transplantation and has the potential to be more effective than standard-dose radioimmunotherapy. Careful dosimetry is required to avoid toxicity and undertreatment. | | Language | eng | | Pub Type(s) | Clinical Trial, Phase I
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
| | PubMed ID | 19255322 |
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