Factors affecting the relationship between the red marrow dose and myelotoxicity in patients receiving radioimmunotherapy with {sup 131}I-labeled anti-CEA monoclonal antibodies
- Center for Molecular Medicine and Immunology, Newark, NJ (United States); and others
This study examined the relationship between the red marrow dose (RMD) and myelotoxicity in patients with CEA-producing tumors who received radioimmunotherapy (RAIT) with {sup 131}I-NP-4 and MN-14 anti-CEA MAbs. Eligibility criteria included no chemotherapy in the last 4 weeks prior to RAIT, no X-irradiation (XT) to >25% of marrow, WBC >3,000, platelets > 100,000, and Hg > 10.0. The RMD was estimated based on blood by assuming a red marrow-to-blood activity concentration ratio of 1.0. Myelotoxicity was evaluated based on standard RTOG criteria. Leukopenia or thrombocytopenia {ge} grade 3 was considered dose-limiting toxicity (DLT). A total of 109 eligible patients were assessed for myelotoxicity. Overall, reversible DLT occurred in 0/14 (0%), 1/25 (4%), 4/26 (15%), 6/25 (24%), 5/9 (55%), 3/6 (50%), and 3/4 (75%) patients receiving a mean RMD of 75, 150, 250, 350, 450, 550, and 650 cGy, respectively. Patients were further stratified into those who had chemotherapy (CHT) in the last 1-6 months prior to RAIT, and/or had XT or tumor metastases to 11-25% of their marrow (group 1), and those who had no CHT in the last 6 months and/or XT or metastases to {ge} 10% of the marrow (group 2). At 250, 350, 450, and 550 cGy, the incidence of DLT in group 1 was 4/17 (23%), 5/11 (45%), 4/4 (100%), and 3/3 (100%), respectively, compared to 0/9 (0%), 1/14 (7%), 1/5 (20%), and 0/3 (0%) in group 2. In conclusion, these data indicate that recent CHT, XT, and marrow metastases are important factors determining myelotoxicity after RAIT. Further, the relatively low incidence of myelotoxicity in group 2 (1/8, 12/5%) DLT at a RMD of 450-550cGy suggests that these patients may be able to tolerate an almost 2-fold higher dose than those in group 1. Although further refinement in identifying risk-factors for myelotoxicity are necessary, these results provide important insights for future planning of phase II trials.
- OSTI ID:
- 447731
- Report Number(s):
- CONF-960659--; CNN: Grant CA 39841; Grant CA 54425
- Journal Information:
- Journal of Nuclear Medicine, Journal Name: Journal of Nuclear Medicine Journal Issue: Suppl.5 Vol. 37; ISSN 0161-5505; ISSN JNMEAQ
- Country of Publication:
- United States
- Language:
- English
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