Tositumomab and I-131 (Bexxar)

Note: GlaxoSmithKline has discontinued the manufacture and sale of the BEXXAR therapeutic regimen (tositumomab and iodine I 131 tositumomab) as of February 2014. More information here.

General information

Class/mechanism: Radioimmunotherapy; treatment regimen that includes two separate steps: first, a dosimetric dose with an anti-CD20 antibody (tositumomab) alone, and second, a therapeutic dose with tositumomab bound to a radioactive isotope, iodone-131 (I-131). Tositumomab binds to the extracellular domain of the CD20 molecule expressed on B-cells and may induce complement-dependent cytotoxicity (CDC) and/or antibody-dependent cell mediated cytotoxicity (ADCC). The I-131 that is bound to tositumomab emits ionizing radiation, leading to cell death.
Route: IV
Extravasation: no information

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.

Diseases for which it is used

Because this medication has been discontinued, these regimens are here for historical reference only. If the medication is ever placed back on the market, we will move the regimens back to their respective page.

• Follicular lymphoma

CHOP -> ¹³¹Iodine-Tositumomab (Bexxar)

CHOP: Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone
CHOP-RIT: Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone RadioImmunoTherapy

Regimen, Press et al. 2003 (SWOG S9911) & Press et al. 2013 (SWOG S0016)

Phase III

CHOP

• Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
• Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
• Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
• Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

Supportive medications:

• Allopurinol (Zyloprim) 300 mg PO once per day for patients with bulky disease

21-day cycles x 6 cycles, followed by:

Tositumomab & I-131 (Bexxar) dosimetric step

• On Day 1, infusions of:
  • Tositumomab 450 mg IV over 1 hour
  • Tositumomab 35 mg labeled with 5 mCi of Iodine-131 IV over 20 minutes
  • First scan of whole body dosimetry & redistribution within 1 hour of finishing dosimetric dose on day 1
• Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
• Day 6 or 7: Third scan of whole body dosimetry & redistribution

Supportive medications:

• Acetaminophen (Tylenol) 650 mg PO as premedication for Tositumomab & I-131 (Bexxar)
• Diphenhydramine (Benadryl) 50 mg PO as premedication for Tositumomab & I-131 (Bexxar)
• Potassium iodide (SSKI, saturated solution of potassium iodide) 4 drops PO TID, Lugol solution 20 drops PO TID, or potassium iodide tablets 130 mg PO once per day starting at least 24 hours before the dosimetric step and continuing for 14 days after the therapeutic infusion

Tositumomab & I-131 (Bexxar) therapeutic step

• Any one day 7 to 14 days after dosimetric infusion, infusions of:
  • Tositumomab 450 mg IV over 1 hour, given first
  • Tositumomab 35 mg labeled with an individually calculated dose of Iodine-131 that will provide 75 cGy of radiation to the total body IV over 20 minutes
    • 65 cGy total body dose used for patients with platelet counts of 100 to 150,000/mm3

Calculated dose of I-131 is based on information from serial total-body gamma-camera counts

Supportive medications:

• Acetaminophen (Tylenol) 650 mg PO as premedication for Tositumomab & I-131 (Bexxar)
• Diphenhydramine (Benadryl) 50 mg PO as premedication for Tositumomab & I-131 (Bexxar)
• Potassium iodide (SSKI, saturated solution of potassium iodide) 4 drops PO TID, Lugol solution 20 drops PO TID, or potassium iodide tablets 130 mg PO once per day starting at least 24 hours before the dosimetric step and continuing for 14 days after the therapeutic infusion

References

1. Press OW, Unger JM, Braziel RM, Maloney DG, Miller TP, LeBlanc M, Gaynor ER, Rivkin SE, Fisher RI. A phase 2 trial of CHOP chemotherapy followed by tositumomab/iodine I 131 tositumomab for previously untreated follicular non-Hodgkin lymphoma: Southwest Oncology Group Protocol S9911. Blood. 2003 Sep 1;102(5):1606-12. Epub 2003 May 8. link to original article contains verified protocol PubMed
2. Update: Press OW, Unger JM, Braziel RM, Maloney DG, Miller TP, Leblanc M, Fisher RI; Southwest Oncology Group. Phase II trial of CHOP chemotherapy followed by tositumomab/iodine I-131 tositumomab for previously untreated follicular non-Hodgkin's lymphoma: five-year follow-up of Southwest Oncology Group Protocol S9911. J Clin Oncol. 2006 Sep 1;24(25):4143-9. Epub 2006 Aug 8. link to original article PubMed
3. Press OW, Unger JM, Rimsza LM, Friedberg JW, Leblanc M, Czuczman MS, Kaminski M, Braziel RM, Spier C, Gopal AK, Maloney DG, Cheson BD, Dakhil SR, Miller TP, Fisher RI. Phase III Randomized Intergroup Trial of CHOP Plus Rituximab Compared With CHOP Chemotherapy Plus 131Iodine-Tositumomab for Previously Untreated Follicular Non-Hodgkin Lymphoma: SWOG S0016. J Clin Oncol. 2013 Jan 20;31(3):314-20. Epub 2012 Dec 10. link to original article contains partial protocol PubMed

CVP -> ¹³¹Iodine-Tositumomab (Bexxar)

CVP: Cyclophosphamide, Vincristine, Prednisone

Regimen

Phase II

CVP

• Cyclophosphamide (Cytoxan) 400 mg/m2 PO once per day on days 1 to 5
• Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
• Prednisone (Sterapred) 100 mg/m2 PO once per day on days 1 to 5

21-day cycles x 6 cycles, followed within 56 days by:

Tositumomab & I-131 (Bexxar) dosimetric step

• On Day 1, infusions of:
  • Tositumomab 450 mg IV over 1 hour
  • Tositumomab 35 mg labeled with 5 mCi of Iodine-131 IV over 20 minutes
  • First scan of whole body dosimetry & redistribution within 1 hour of finishing dosimetric dose on day 1
• Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
• Day 6 or 7: Third scan of whole body dosimetry & redistribution

Supportive medications:

• Acetaminophen (Tylenol) 650 mg PO as premedication for Tositumomab & I-131 (Bexxar)
• Diphenhydramine (Benadryl) 50 mg PO as premedication for Tositumomab & I-131 (Bexxar)
• Potassium iodide (SSKI, saturated solution of potassium iodide) 4 drops PO TID, Lugol solution 20 drops PO TID, or potassium iodide tablets 130 mg PO once per day starting at least 24 hours before the dosimetric step and continuing for 14 days after the therapeutic infusion

Tositumomab & I-131 (Bexxar) therapeutic step

• Any one day 7 to 14 days after dosimetric infusion, infusions of:
  • Tositumomab 450 mg IV over 1 hour, given first
  • Tositumomab 35 mg labeled with an individually calculated dose of Iodine-131 that will provide 75 cGy of radiation to the total body IV over 20 minutes
    • 65 cGy total body dose used for patients with platelet counts of 100 to 150,000/mm3

Calculated dose of I-131 is based on information from serial total-body gamma-camera counts

Supportive medications:

• Acetaminophen (Tylenol) 650 mg PO as premedication for Tositumomab & I-131 (Bexxar)
• Diphenhydramine (Benadryl) 50 mg PO as premedication for Tositumomab & I-131 (Bexxar)
• Potassium iodide (SSKI, saturated solution of potassium iodide) 4 drops PO TID, Lugol solution 20 drops PO TID, or potassium iodide tablets 130 mg PO once per day starting at least 24 hours before the dosimetric step and continuing for 14 days after the therapeutic infusion

References

1. Link BK, Martin P, Kaminski MS, Goldsmith SJ, Coleman M, Leonard JP. Cyclophosphamide, vincristine, and prednisone followed by tositumomab and iodine-131-tositumomab in patients with untreated low-grade follicular lymphoma: eight-year follow-up of a multicenter phase II study. J Clin Oncol. 2010 Jun 20;28(18):3035-41. Epub 2010 May 10. link to original article PubMed .

Fludarabine -> ¹³¹Iodine-Tositumomab (Bexxar)

Regimen

Phase II

• Fludarabine (Fludara) 25 mg/m2 IV once per day on days 1 to 5

5-week cycles x 3 cycles, followed by:

Dosimetric step

• On Day 0, infusions of:
  • Tositumomab 450 mg IV over 1 hour
  • Tositumomab 35 mg labeled with 5 mCi of Iodine-131 IV over 20 minutes
  • First scan of whole body dosimetry & redistribution
• Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
• Day 6 or 7: Third scan of whole body dosimetry & redistribution

Therapeutic step

• Any day from day 7 to 14, infusions of:
  • Tositumomab 450 mg IV over 1 hour
  • Tositumomab 35 mg labeled with an individually calculated dose of Iodine-131 that will provide 75 cGy of radiation to the total body IV over 20 minutes
    • 65 cGy total body dose used for patients with platelet counts of 100 to 150,000/mm3

Calculated dose of I-131 is based on information from serial total-body gamma-camera counts

References

1. Leonard JP, Coleman M, Kostakoglu L, Chadburn A, Cesarman E, Furman RR, Schuster MW, Niesvizky R, Muss D, Fiore J, Kroll S, Tidmarsh G, Vallabhajosula S, Goldsmith SJ. Abbreviated chemotherapy with fludarabine followed by tositumomab and iodine I 131 tositumomab for untreated follicular lymphoma. J Clin Oncol. 2005 Aug 20;23(24):5696-704. link to original article contains verified protocol PubMed

¹³¹Iodine-Tositumomab (Bexxar)

Regimen

Phase II

Dosimetric step

• On Day 0, infusions of:
  • Tositumomab 450 mg IV over 1 hour
  • Tositumomab 35 mg labeled with 5 mCi of Iodine-131 IV over 20 minutes
  • First scan of whole body dosimetry & redistribution
• Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
• Day 6 or 7: Third scan of whole body dosimetry & redistribution

Therapeutic step

• Any day from day 7 to 14, infusions of:
  • Tositumomab 450 mg IV over 1 hour
  • Tositumomab 35 mg labeled with an individually calculated dose of Iodine-131 that will provide 75 cGy of radiation to the total body IV over 20 minutes
    • 65 cGy total body dose used for patients with platelet counts of 100 to 150,000/mm3

Calculated dose of I-131 is based on information from serial total-body gamma-camera counts

References

1. Kaminski MS, Tuck M, Estes J, Kolstad A, Ross CW, Zasadny K, Regan D, Kison P, Fisher S, Kroll S, Wahl RL. 131I-tositumomab therapy as initial treatment for follicular lymphoma. N Engl J Med. 2005 Feb 3;352(5):441-9. link to original article contains verified protocol PubMed
2. Update: Mark S. Kaminski, MD, Melissa Tuck, MS, Judith Estes, BSN, MSN, Arne Kolstad, MD, PhD, Charles Warren Ross, MD, Denise Regan, BS, Thierry Horner, PhD, Vanessa C. Williams, MS, Tina Vleisides, DC and Richard L. Wahl, MD. Tositumomab and Iodine I-131 Tositumomab for Previously Untreated, Advanced-Stage, Follicular Lymphoma: Median 10 Year Follow-up Results. ASH 2009 abstract 3759.

¹³¹Iodine-Tositumomab (Bexxar)

Regimen

Phase II

Dosimetric step

• On Day 0, infusions of:
  • Tositumomab 450 mg IV over 1 hour
  • Tositumomab 35 mg labeled with 5 mCi of Iodine-131 IV over 20 minutes
  • First scan of whole body dosimetry & redistribution
• Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
• Day 6 or 7: Third scan of whole body dosimetry & redistribution

Therapeutic step

• Any day from day 7 to 15, infusions of:
  • Tositumomab 450 mg IV over 1 hour
  • Tositumomab 35 mg labeled with an individually calculated dose of Iodine-131 that will provide 75 cGy of radiation to the total body IV over 20 minutes
    • 65 cGy total body dose used for patients with platelet counts of 100 to 150,000/mm3

Calculated dose of I-131 is based on information from serial total-body gamma-camera counts

Supportive medications:

• Acetaminophen (Tylenol) 650 mg PO as premedication for Tositumomab & I-131 (Bexxar)
• Diphenhydramine (Benadryl) 50 mg PO as premedication for Tositumomab & I-131 (Bexxar)
• Potassium iodide (SSKI, saturated solution of potassium iodide) 2 drops PO TID starting at least 24 hours before the dosimetric step and continuing for 14 days after the therapeutic infusion; may also use Lugol’s solution or potassium iodide tablets

References

1. Kaminski MS, Zelenetz AD, Press OW, Saleh M, Leonard J, Fehrenbacher L, Lister TA, Stagg RJ, Tidmarsh GF, Kroll S, Wahl RL, Knox SJ, Vose JM. Pivotal study of iodine I 131 tositumomab for chemotherapy-refractory low-grade or transformed low-grade B-cell non-Hodgkin's lymphomas. J Clin Oncol. 2001 Oct 1;19(19):3918-28. link to original article contains verified protocol PubMed
2. Fisher RI, Kaminski MS, Wahl RL, Knox SJ, Zelenetz AD, Vose JM, Leonard JP, Kroll S, Goldsmith SJ, Coleman M. Tositumomab and iodine-131 tositumomab produces durable complete remissions in a subset of heavily pretreated patients with low-grade and transformed non-Hodgkin's lymphomas. J Clin Oncol. 2005 Oct 20;23(30):7565-73. Epub 2005 Sep 26. link to original article PubMed

Patient drug information

• Tositumomab and I-131 (Bexxar) patient drug information (Chemocare)
• Tositumomab and I-131 (Bexxar) patient drug information (UpToDate)

History of changes in FDA indication

• 6/27/2003: Granted FDA accelerated approval for the treatment of patients with CD20 positive, follicular, non-Hodgkin's lymphoma, with and without transformation, whose disease is refractory to Rituximab (Rituxan) and has relapsed following chemotherapy.
• 12/22/2004: FDA labeling revised to include patients with relapsed or refractory, low grade, follicular or transformed CD20 positive non-Hodgkin's lymphoma who have not received Rituximab (Rituxan)
• 8/15/2012: FDA labeling revised to remove 12/22/2004 addition for rituximab-naive patients.

Also known as

• BEXXAR
• tositumomab and I 131 tositumomab
• tositumomab and iodine-131 tositumomab.