Bob L & Biowa,
My take on the Zev dosimetry is that they've never modified the dose based on this, they've simply used it to validate that the standard dose will be safe for each patient. Here's some stuff from the Zevalin paper Bob pointed us to - interestingly, it looks like one patient was not treated due to the local dosimetry results, although they say that the centralized analysis indicated the patient could have been treated.
Dosimetry calculations to determine the safety of treatment were performed before treatment at the individual study sites. Central dosimetry was performed by the Mayo Clinic and Oak Ridge Institute for Science and Education. <snip>
Patients received rituximab and IDEC-In2B8 on day 0 followed by gamma camera imaging on days 0 through 6. If the predicted delivered dose of radiation to any nontumor organ was more than 20 Gy or if the dose to the bone marrow was more than 3 Gy, no treatment with IDEC-Y2B8 was to be administered. <snip>
One patient was not treated based on site-specific (non-MIRDOSE), image-based, bone marrow dosimetry, although the estimated marrow radiation dose was acceptable on blood-derived and sacral image?derived MIRDOSE3 dosimetry performed by the central dosimetrist (Oak Ridge Institute for Science and Education).
I suppose that doesn't bode well for eliminating the 111In dosimetry entirely, although that seems to be their intention, as indicated in a press release from last year's ASH:
MIAMI BEACH, FL--(BW HealthWire)--Dec. 7, 1998 <snip>
In the first of two posters presented, principal investigators Gregory Wiseman, M.D. and Thomas Witzig, M.D. of the Mayo clinic, Rochester, MN, concluded that simple clinical parameters such as baseline platelet count and degree of bone marrow involvement with lymphoma may be used in place of dosimetry, a complex analysis of radiation uptake in major organs, for safe administration of the investigational agent, IDEC-Y2B8, in patients with low grade or follicular non-Hodgkin's lymphoma. The greatest risk of systemic radioimmunotherapy has been potential damage to normal organs. Bone marrow is particularly sensitive to radiation. Dosimetry, which consists of multiple gamma scans, measurements and calculations, is required to determine the appropriate amount of radioisotope to deliver with certain other radioimmunotherapy investigational agents.
Rather than using dosimetry to select dose, IDEC-Y2B8 clinical trial dosing is standardized, based primarily on body weight and platelet count. <snip>
The new findings presented at ASH showed that baseline platelet count and bone marrow involvement are better predictors of hematologic toxicity than dosimetry for this investigational agent. "The implications for IDEC-Y2B8 appear promising," said William R. Rohn, IDEC's chief operating officer. "The clinical experience to date suggests that IDEC-Y2B8 administration could be streamlined for most patients, reducing potential cost and complexity without increasing safety risk." The company is currently conducting two pivotal trials, one with and one without dosimetry. Dosimetry is being used in one trial to further validate the standardized dosing procedure for IDEC-Y2B8.
The trial "without dosimetry" would have to be the Zev vs. Rituxan trial, if we were to see the protocol for that trial then we might be able to verify our understanding of this... Are they really not using 111In at all in that trial, or is this a press flack mis-statement?
Speaking of ASH, I'm here in New Orleans to attend for a couple of days, I'll try to pass along anything of interest that I run across. Will be paying closest attention to CLTR and IDEC issues, but will also pay some attention to stuff regarding CELG, LKST/ILXO, PDLI and LGND. Today is "corporate propaganda day" (heheh, just my term, really it's corporate sponsored symposiums) - I'm off now to check out the Coulter/SmithKline propaganda and brainwashing session. ;-)
Cheers,
Gordon |
