NMR metabolic and physiological markers of therapeutic response.

Identification of reliable metabolic and physiological NMR detectable markers for prediction and early detection of therapeutic response is essential to enabling NMR guided individualized therapy for cancer. Because non-Hodgkin's lymphoma (NHL) is a prevalent form of cancer that exhibits~50% response to therapy and often presents with large superficial lesions easily accessible to multinuclear magnetic resonance spectroscopy (MRS) measurements, it is an ideal test bed for development of NMR methods for prediction and early detection of response.A multicenter study, in which we have participated, has already shown that pre-treatment(31) PMRS measurement of the phosphate monoester (PME)to nucleoside triphosphate (NTP) ratio can identify about 2/3 of the patients who are destined not to exhibit a complete clinical response to a variety of therapeutic agents.Because (31)PMRS is limited to relatively large superficial tumors, we have been exploring (1)HMRS and MRI methods for early detection of therapeutic response. Using xenografts of the most common form of human NHL, diffuse large B-cell lymphoma (DLBCL), we have detected therapeutic response within one cycle of therapy with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), rituximab plus CHOP (RCHOP) or radiation (15 Gy) through detection of a decrease in lactic acid (Lac) or total choline (tCho) and an increase of apparent diffusion coefficients (ADC). We have also performed (1)H MRS of NHL patients in a clinical scanner. One of the patients exhibited a 70% decrease in Lac within 48 h of treatment with RCHOP.

Factors associated with toxicity and response to yttrium 90-labeled ibritumomab tiuxetan in patients with indolent non-Hodgkin's lymphoma.

Treatment of patients with indolent non-Hodgkin's lymphoma (NHL) is evolving. These patients usually present with advanced-stage disease. Treatment options for patients who experience relapse are limited, and no treatment has been shown to be superior to others in improving overall survival of this group of patients, with the possible exception of allogeneic stem cell transplantation. Therefore, new approaches are needed to improve outcomes in patients with relapsed or refractory disease. The anti-CD20 monoclonal antibody, rituximab, was the first monoclonal antibody approved for the treatment of indolent B-cell NHL. As a single agent in the treatment of relapsed or refractory indolent lymphoma, response rates as high as 56% have been observed. This promising new therapy was followed by development of radioimmunotherapy, a novel treatment approach that combines the targeting capability of monoclonal antibodies with the additional cytotoxic effects of radiation. Yttrium 90-labeled ibritumomab tiuxetan (Zevalin) is a radiolabeled monoclonal antibody that has been shown to produce clinically significant responses in up to 80% of patients with indolent NHL and is the first radiolabeled monoclonal antibody approved for therapeutic use in the treatment of lymphoma. This article reviews some of the safety and efficacy data for this agent in addition to examining factors that could aid in predicting response and toxicity in patients with low-grade relapsed or refractory NHL treated with 90Y ibritumomab tiuxetan.