Bevacizumab given in addition to the combined chemotherapy regimen of gemcitabine and oxaliplatin (GEMOX-B) is well tolerated and shows promising antitumour activity in patients with advanced biliary-tract cancers. The survival and tumour response reported in an article published Online First in the Lancet Oncology compare favourably with previous studies in patients treated with GEMOX alone and require further investigation in randomised trials.

Systemic chemotherapy is the standard treatment for patients with advanced biliary-tract cancers. But the prognosis for these patients remains poor and better therapies are needed. Previous studies have shown that a combined chemotherapy regimen of gemcitabine and oxaliplatin (GEMOX) delays disease progression and 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, and might enhance chemotherapy in patients with biliary-tract cancers by slowing down the growth of tumours and improving delivery of chemotherapy.

To investigate the effectiveness and safety of GEMOX-B in patients with biliary-tract cancers, Andrew X Zhu from Massachusetts General Hospital Cancer Center, Boston, USA and colleagues conducted a phase 2 trial. The authors also examined the potential of changes in whole-body PET scans as an early predictive marker of clinical outcome to help identify which patients are most likely to benefit from the treatment.

In total, 35 patients with advanced biliary-tract cancers were given all three drugs intravenously (bevacizumab 10 mg/kg, followed by gemcitabine 1000 mg/m² and oxaliplatin 85 mg/m²) on days 1 and 15, every 28 days. Whole-body PET scans were done at the start of the trial and at the end of the second cycle of therapy. Treatment was continued until unacceptable toxicity, disease progression, or patient refusal.

Findings showed that GEMOX-B had good tumour response with an overall response rate of 40% (14 patients with confirmed partial responses) and stable disease was observed in an additional ten patients (29%). Overall survival was 12.7 months and median progression-free survival (PFS) was 7 months. However, PFS at 6 months was 63%, which was below the targeted rate.

GEMOX-B therapy was generally well tolerated with grade 3-4 toxicities not exceeding 20% in any categories. The most common adverse events were fatigue, neutropenia (an abnormally low number of white blood cells), peripheral neuropathy, high blood pressure, and gastrointestinal events.

Importantly, whole-body PET scans were found to be very sensitive in patients with biliary-tract cancers and showed promising results for monitoring treatment response. PET scans showed a significant decrease in the mean maximum standardised uptake value (SUVmax) of 18-fluorodeoxyglucose within lesions after two cycles of treatment. These changes were more pronounced in patients with partial response and stable disease than those with progressive disease and change in SUVmax following treatment was shown to be a significant predictor of PFS and overall survival.

The authors conclude that these findings add to the “[i]ncreasing data supporting the combination of molecularly targeted agents with chemotherapy to further improve treatment outcomes in patients with biliary-tract cancers.”

Date: November 23, 2009
Source: Lancet