From OncoLog, October 2012, Vol. 57, No. 10

In Brief 

Bevacizumab With High-Dose Chemotherapy Shows Promise for Cisplatin Refractory Germ Cell Tumors

Bevacizumab given concurrently with high-dose chemotherapy elicits encouraging results in patients with treatment-refractory germ cell tumors, according to the preliminary results of an ongoing phase II study.

Although high-dose chemotherapy alone is curative for many patients with recurrent germ cell tumors, a low rate of event-free survival is seen in patients with recurrent disease whose tumors have developed cisplatin resistance or who present with high levels of tumor markers at the time of relapse.

The purpose of the study was to determine whether the addition of the antiangiogenic drug bevacizumab to high-dose chemotherapy helps control germ cell tumors. Bevacizumab inhibits vascular endothelial growth factor, a protein that is highly expressed in metastatic germ cell tumors. Bevacizumab also increases drug penetration into tumors.

The 23 patients enrolled so far in the study have undergone a median of 4 prior chemotherapy regimens (range, 2–6 regimens). Sixteen of the patients have undergone prior surgery to remove metastases. The patients received bevacizumab (5 mg/kg) 1 week before each of 2 cycles of high-dose chemotherapy with stem cell support. The first chemotherapy cycle consisted of a novel regimen of gemcitabine with docetaxel, melphalan, and carboplatin; the second cycle consisted of ifosfamide, carboplatin, and etoposide. Patients received an autologous stem cell infusion after each cycle.

The most prominent side effect of the first cycle of high-dose chemotherapy was mucositis, which resolved. Three patients died of infections unrelated to their tumors following the first cycle of chemotherapy.

Of the remaining 18 patients, 15 received the second cycle of high-dose chemotherapy at a median of 49 days (range, 38–66 days) after their first stem cell infusion. All patients tolerated the second chemotherapy cycle well. Residual lesions were resected in 8 patients, with biopsy findings of necrosis or mature teratoma in all cases. At a median follow-up time of 25 months, the event-free survival rate was 68%.

Researchers from The University of Texas MD Anderson Cancer Center presented the study’s preliminary results in an abstract at the annual meeting of the American Society of Clinical Oncology in June.