Researchers from the Robert H Lurie Comprehensive Cancer Center have reported that the addition of Xcytrin® to Zevalin® ([90Y] ibritumomab tiuxetan) may improve treatment of patients with relapsed or refractory non-Hodgkin’s lymphoma (NHL). The details of this study appeared early online in Clinical Cancer Research.[1]

Cancers often consist of areas of low oxygen concentration, which complicates treatment. Hypoxic cells are more resistant to the effects of radiation than well-oxygenated tissues. There have been many candidate drugs for increasing oxygenation of cancers (radiosensitizers), none of which have been very successful. Xcytrin is a new type of radiation sensitizer that sensitizes both oxygenated and hypoxic cells to the effects of radiation. Xcytrin also localizes selectively in tumors, which can be detected by magnetic resonance imaging. Laboratory and preclinical studies suggested that Xcytrin could potentiate the effects of radiation for the treatment of cancers. A Phase II study of Xcytrin and whole-brain radiation therapy (WBRT) suggested improved responses compared with historical controls. A Phase III trial suggested that Xcytrin plus WBRT prolonged time to neurologic progression in patients with non–small cell lung cancer metastatic to the brain compared with patients receiving WBRT alone.[2] 

Zevalin is a murine IgG1 kappa monoclonal antibody conjugated to tiuxetan (MXDTPA) that chelates yttrium or indium and is directed against the CD 20 molecules of B lymphocytes. Rituxan® (rituximab), 250 mg/m2, is usually given seven days and one day before Zevalin. Zevalin can be administered with or without stem cell support, depending of the dose used. The rationale for using a targeted radio-labeled isotope is to decrease toxicity by the delivery of more specific radiotherapy. Zevalin is one of the most active treatments available for patients with NHL, but the need for nuclear medicine monitoring has led to less than predicted use in the general oncology community.

In the current study, researchers reported that in-vitro studies suggested synergistic effects of Xcytrin and Zevalin on lymphoma cells. Thirty patients with refractory or relapsed NHL were included in the Phase I trial. The age range was 47-87 years with a median of 65 years. The majority of patients had follicular lymphoma, and 86% were resistant to Rituxan. The complete response rate was 43%, and the overall response rate was 57%. Median time to treatment failure was 10 months. For 14 patients with Rituxan-refractory disease, the complete response rate was 64% and median time to treatment failure was 14 months.

Comments: These are interesting data because of the high complete response rate in patients with Rituxan-refractory disease. However, Zevalin alone is very active in this group of patients, and further studies will be needed to determine the additive effects of Xcytrin.

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