Is combination therapy of imatinib (Gleevec) and radiotherapy safe?

—Nazanin Nouriany, RN, MScN, CCRP

Cytotoxic chemotherapy agents have been combined with radiotherapy for many years; this treatment approach is termed chemoradiation. The intent of chemoradiation is to potentiate the effects of radiation on cancer cells and increase cancer cell death. Cytotoxic chemotherapy agents such as the fluoropyrimidines (eg, fluorouracil, capecitabine [Xeloda]), taxanes (eg, paclitaxel [Taxol]), and platinum agents (eg, cisplatin) are the agents typically used for this purpose. These chemotherapy agents increase the anticancer effects of radiotherapy by making cellular DNA more susceptible to damage, interfering with cellular repair, or by causing cancer cells to remain in a phase of their growth cycle in which they are more sensitive to the effects of radiation. Due to their differing mechanism of anticancer activity, targeted chemotherapy agents are not typically used in chemoradiation regimens. There is, however, some data to suggest that imatinib specifically may potentiate the anticancer effects of radiation in select cancers1,2; clinical studies of these combinations are ongoing.

There is concern that patients who receive targeted chemotherapy agents while receiving radiotherapy may experience increased toxicity. For example, patients receiving radiation to a large portion of their bone marrow may be at increased risk for neutropenia due to the myelosuppressive effects of both treatments, and patients receiving radiation to mucous membranes may have an increased risk of mucositis. The decision to continue treatment with a targeted agent such as imatinib during radiotherapy is dependent on the risk:benefit ratio for that patient. Many patient- and treatment-specific factors may affect the risks of continuing targeted therapy, such as the patient’s chemotherapy history, the targeted agent being used, the disease state being treated by the targeted agent, and the intended dose, duration, and method of radiation delivery. Both medical oncology and radiation oncology providers should be involved in the decision to continue treatment.


Lisa Thompson is a clinical pharmacy specialist in oncology at Kaiser Permanente, Colorado.  


REFERENCES

1. Oertel S, Krempien R, Lindel K, et al. Human glioblastoma and carcinoma xenograft tumors treated by combined radiation and imatinib (Gleevec). Strahlenther Onkol. 2006;182(7):400-407.

2. Choudhury A, Zhao H, Jalali F, et al. Targeting homologous recombination using imatinib results in enhanced tumor cell chemosensitivity and radiosensitivity. Mol Cancer Ther. 2009;8(1):203-213.