Radiation Oncology/Radioimmunotherapy

Forms of RIT

• Zevalin - ibritumomab, Y-90 labeled murine antibody. Pure beta emitter, 64 hr half life.
• Bexxar - tositumomab, I-131 labeled murine antibody, beta and gamma, 8 day half life. Dose is based on individual patient dosimetry (pharmacokinetics).

Rituxan - rituxumab, unlabeled chimeric anti-CD20 antibody.

Administration

Bexxar

Steps:

• Dosimetric step - infusion of unlabled antibody (tositumomab, not rituxumab, 450 mg) followed by 5 mCi dose of I-131-tositumomab.
• Whole body imaging on Day 0 (day of dosimetric step), day 2-4, and day 6 or 7. If biodistribution is acceptable, then calculate patient specific dose to deliver 75 cGy (or 65 cGy if plts 100,000-150,000).
• 
  Therapeutic step - 7-14 days after dosimetric step. 2nd infusion of unlabeled antibody followed by patient-specific dose of I-131-tositumomab to deliver 65-75 cGy total body dose.

Patient selection:

• Should not be administered to patients with >25% bone marrow involvement and/or impaired bone marrow reserve.
• Caution should be exercised in patients with impaired renal function.
• Do not administer if there is altered biodistribution (see below).

Thyroid protection:
Begin the day prior to dosimetric step. Continue through 14 days after therapeutic dose.

Dosimetry:
Whole body images obtained with gamma camera every 3 days to determine total body residence time (TBRT), reflecting clearance of the radioisotope. Count 1 is within an hour of the infusion of the dosimetric dose; Count 2 is 2-4 days after dosimetric dose.
Assess whole body images for Counts 1 and 2 (and optionally Count 3) to see if there is altered biodistribution. If there is altered biodistribution based on the images or the TBRT, then Bexxar should not be administered.
Expected biodistribution: 1st Image: most of the activity is in the blood pool (heart and major vessels), and uptake in the normal liver and spleen is less than the heart. On 2nd and 3rd images, blood pool activity and liver activity decreases. Uptake by thyroid, kidney, urinary bladder, and minimal lung uptake.
Altered biodistribution:

• 1st image: if blood pool is not visualized or if there is diffuse, intense uptake in the liver and/or spleen or if there is a suggestion of urinary obstruction. If there is diffuse lung uptake greater than that of the blood pool.
• 2nd and 3rd images: urinary obstruction or diffuse lung uptake greater than that of blood pool.
• TBRT <50 hrs or >150 hrs

Dose adjustments:
For platelet count >= 150,000, total body dose is 75 cGy. For platelets 100,000-150,000, total body dose is 65 cGy.
For obese patients (weight > 137% of ideal body weight), dose should be based on 137% of their lean body weight.

Treatment

See also specific treatment information at:

• Radiation Oncology/NHL/Follicular

For recurrence:

• U. Washington - PMID 17312330, 2007 — "High-Dose [131I]Tositumomab (anti-CD20) Radioimmunotherapy and Autologous Hematopoietic Stem-Cell Transplantation for Adults ≥ 60 Years Old With Relapsed or Refractory B-Cell Lymphoma." Gopal AK et al. J Clin Oncol. 2007 Apr 10;25(11):1396-402.
  • 24 pts. Pts older > 60 yrs, relapsed B-cell NHL (s/p median of 4 prior regimens). Rituxan + Bexxar followed by ASCT.
  • Median f/u 2.9 yrs. 3-yr OS and PFS 59% and 51%. 2 pts with grade 4 hematologic toxicity.
  • Conclusion: safe and effective treatment for older adults

Lutetium-177

¹⁷⁷Lu-octeotrate

• Erasmus; 2008 (Netherlands)(2000-2006) PMID 18445841 -- "Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival." (Kwekkeboom DJ, J Clin Oncol. 2008 May 1;26(13):2124-30.)
  • Retrospective. 504 patients with gastroenteropancreatic neuroendocrine tumors (GEPNETs). Up to cumulative dose 750-800 mCi (27.8-29.6 GBq), usually in 4 cycles with intervals 6-10 weeks
  • Outcome: CR 2%, PR 38%. Median TTP
  • Toxicity: Grade 3+ hematologic in 4%, MDS in 3 patients 3.3 years, median OS 3.8 years (compared to historical controls, survival benefit of 3.3-6 years from diagnosis)
  • Conclusion: Few adverse effects, response rate and PFS compare favorably to historical controls