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Pilot Study Evaluates Concurrent Use of Sunitinib and Radiation Therapy in Recurrent High-Grade Glioma

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Key Points

  • Recurrent glioblastoma multiforme is among the more challenging cancers to treat, with systemic cytotoxic agents demonstrating limited efficacy.
  • Concurrent treatment with sunitinib and hypofractionated stereotactic radiation yielded a 6-month progression-free survival of 45% in patients with recurrent high-grade glioma, according to the results of a small pilot study.
  • The combination therapy produced acceptable toxicity, with the most common side effects being low-grade hematologic disorders and fatigue.

The combination of continuous daily-dosed sunitinib (Sutent) and hypofractionated stereotactic radiation therapy produced acceptable toxicity and “encouraging” 6-month progression-free survival in previously irradiated patients with recurrent high-grade glioma, according to the results of a pilot study reported by Wuthrick et al in the International Journal of Radiation Oncology • Biology • Physics. These findings suggest that a subgroup of patients with recurrent high-grade glioma may attain long-term benefits from this concurrent treatment strategy, which appeared to compare favorably with reirradiation or antiangiogenic agents alone.

Recurrent glioblastoma multiforme is among the more challenging cancers to treat, with systemic cytotoxic agents demonstrating limited efficacy. Thus, the search for effective therapeutic options has led investigators to consider combining different strategies in the hope of improving patient outcomes.

For instance, preclinical studies have suggested that angiogenic blockade with the multitargeted receptor tyrosine kinase inhibitor sunitinib (Sutent) may have an enhanced radiosensitizing effect in patients with glioma, perhaps through vascular normalization. Although the role of reirradiation with conventional radiation therapy is limited by treatment-related toxicity in patients with recurrent disease, newer techniques such as fractionated stereotactic radiation therapy may permit highly conformal treatment with fewer adverse effects.

Study Details

To determine the safety and toxicity profile of continuous daily-dosed sunitinib with fractionated stereotactic radiation therapy for recurrent high-grade glioma, Wuthrick and colleagues conducted a pilot study at the Thomas Jefferson University Hospital Cancer Center. Eleven patients who had confirmed primary glioma that recurred or progressed after surgery and radiation therapy met eligibility criteria. All of these patients had adequate hematologic, hepatic, and renal function.

At least a 10-day course of fractionated stereotactic radiation therapy was received by all study patients. The radiation doses ranged from 30 to 42 Gy in 2.5- to 3.75-Gy fractions, depending on the size of the tumor recurrence, the extent of resection, the size of the resection cavity, and prior doses of radiation therapy. During this time, sunitinib 37.5 mg was given daily. The investigators performed baseline assessments and graded toxicity during active treatment and at 4 weeks after treatment.

No treatment delays were necessary, and all patients completed the prescribed treatment. In addition, six patients (55%) chose to continue daily sunitinib for 30 additional days after the completion of radiation therapy.

‘Encouraging’ Outcomes at 6-Month Follow-up

The most common acute toxicities were low-grade (grade 1 or 2) hematologic disorders (thrombocytopenia, leukopenia) and fatigue. There was one high-grade (> grade 3) toxicity—a nonhealing oral ulcer on the left lateral aspect of the tongue—which required discontinuation of sunitinib. The investigators noted no difference in toxicity based on the total dose of radiation therapy delivered or the fraction size. No severe hypertensive events or intracerebral hemorrhage was reported.

Of the 10 patients who underwent assessment of 1-month tumor response, one patient had a partial response, six patients had stable disease, and three patients had disease progression.

At 6-month follow-up, the cancer had not progressed in 45% of patients, with a median progression-free survival of 5.8 months. As for median overall survival, seven patients (64%) were alive at 6 months post treatment, and five patients (45%) remained alive after 1 year. Three years after treatment, two patients are alive with stable disease.

Closing Thoughts

Continuous daily-dosed sunitinib at 37.5 mg and hypofractionated stereotactic radiation therapy appeared to be safe and tolerable in patients with recurrent high-grade glioma. In fact, toxicity was limited to grades 1 or 2 in more than 90% of patients, and all were able to complete the course of therapy. According to the investigators, the promising outcomes they observed may suggest that some patients with recurrent high-grade glioma may reach prolonged progression-free survival with this treatment strategy.

“We observed that the 2-month magnetic resonance imaging response predicted progression-free and overall survival. The patient who achieved a partial response had a 21.8-month progression-free survival and a 27.5-month overall survival,” concluded the investigators. “Progressive disease at 2-month magnetic resonance imaging was a poor prognostic sign, inasmuch as that cohort’s median overall survival was 6.3 months.”

Evan J. Wuthrick, MD, of the Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, is the corresponding author of the article in the International Journal of Radiation Oncology • Biology • Physics.

This pilot study was supported by grants from Pfizer Inc. The authors disclosed no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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