An article published Online First in The Lancet Oncology reports that bevacizumab given in addition to the combined chemotherapy regimen of gemcitabine and oxaliplatin (GEMOX-B) is well tolerated. In addition, it shows promising antitumor activity in patients with advanced biliary-tract cancers. The article reviews the survival and tumour response that compare favourably with earlier studies in patients treated with GEMOX alone. Further investigation in randomised trials is needed.
For patients with advanced biliary-tract cancers, systemic chemotherapy is the standard treatment. However, improved therapies are needed since the prognosis for these patients remains poor. Prior studies have shown that a combined chemotherapy regimen of gemcitabine and oxaliplatin (GEMOX) delays disease progression. It also has acceptable toxicity in patients with biliary-tract cancers. In addition, bevacizumab (an angiogenisis inhibitor) has been beneficial in the treatment of several cancers including colorectal, breast, and lung. The drug might also improve chemotherapy in patients with biliary-tract cancers by slowing down the growth of tumours and enhancing delivery of chemotherapy.
Andrew X Zhu from Massachusetts General Hospital Cancer Center, Boston, USA and colleagues conducted a phase 2 trial. They investigated the effectiveness and safety of GEMOX-B in patients with biliary-tract cancers. The researchers also examined the potential of changes in whole-body PET scans as an early predictive marker of clinical outcome. This would help identify which patients are most likely to benefit from the treatment.
A total of 35 patients with advanced biliary-tract cancers were given all three drugs intravenously. The treatment was bevacizumab 10 mg/kg, followed by gemcitabine 1000 mg/m² and oxaliplatin 85 mg/m² on days one and fifteen, every twenty-eight days. At the start of the trial and at the end of the second cycle of therapy, whole-body PET scans were done. Treatment was continued until unacceptable toxicity, disease progression, or patient refusal.
The results indicated that GEMOX-B had good tumour response. There was an overall response rate of 40 percent with 14 patients with confirmed partial responses. In addition, stable disease was observed in another ten patients (29 percent). In general survival was 12.7 months and median progression-free survival (PFS) was 7 months. However, PFS at 6 months was 63 percent. This percentage was below the targeted rate.
GEMOX-B therapy was generally well tolerated. In any categories, the grade 3 to 4 in toxicities did not exceed 20 percent. The most frequent adverse events were fatigue, gastrointestinal events, peripheral neuropathy, high blood pressure, and neutropenia which is an abnormally low number of white blood cells.
Significantly, whole-body PET scans were found to be very sensitive in patients with biliary-tract cancers. In addition, they showed promising results for monitoring treatment response. PET scans showed an important decrease in the mean maximum standardised uptake value (SUVmax) of 18-fluorodeoxyglucose within lesions after two cycles of treatment. These changes were more prominent in patients with partial response and stable disease than those with progressive disease. Change in SUVmax following treatment was shown to be a significant predictor of PFS and overall survival.
In closing, the authors write that these findings add to the: “Increasing data supporting the combination of molecularly targeted agents with chemotherapy to further improve treatment outcomes in patients with biliary-tract cancers.”
“Efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome: a phase 2 study”
Andrew X Zhu, Jeffrey A Meyerhardt, Lawrence S Blaszkowsky, Avinash R Kambadakone, Alona Muzikansky, Hui Zheng, Jeffrey W Clark, Thomas A Abrams, Jennifer A Chan, Peter C Enzinger, Pankaj Bhargava, Eunice L Kwak, Jill N Allen, Sanjay R Jain, Keith Stuart, Kerry Horgan, Susan Sheehan, Charles S Fuchs, David P Ryan, Dushyant V Sahani
DOI: 10.1016/S1470-2045(09)70333-X
Written by Stephanie Brunner (B.A.)