Prospective phase II study of capecitabine and temozolomide (CAPTEM) for progressive, moderately, and well-differentiated metastatic neuroendocrine tumours (Haelio, 15 January 2014)

Data from the CAPTEM trial was presented at GI ASCO this month.

The investigators demonstrated that capecitabine and temozolomide were synergistic in inducing apoptosis in neuroendocrine tumour cell lines. This led to the development of this prospective phase II clinical trial. The interim results were presented this month.

28 patients with metastatic, well-moderately differentiated NET (ki-67 ≤20%) and who had shown progression only on 60mg Sandostatin LAR (if octreotide scan positive) were treated with the following regimen: CAP 1,500mg/m2/day (PO divided BID, maximum 2,500 mg/day) between day 1-14; TEM 150-200mg/m2/day (PO divided BID, lower dose for patients who had prior chemotherapy or extensive radiation) between days 10-14, with the next two weeks off, over a 28 day cycle.

The primary objective was radiological response based upon RECIST, and secondary objectives included PFS, OS (from time of initiation of therapy), and toxicity evaluation. Among the study population, 12 patients had carcinoid tumours, three had pituitary tumours, 11 had peripheral neuroectodermal tumours and two had medullary thyroid tumours.

Overall RR was 43% (11% CR) and SD rate was 54%, with clinical benefit in 97%. ORR was 41% in carcinoid tumours. Ongoing mPFS is >20mo for all subtypes with 18/28 (64%) having progressed at this time. The ongoing median PFS is more than 20 months, and the ongoing median OS is more than 25.3 months. Twelve of 28 had died at this analysis. Among patients with carcinoid tumours, 41% demonstrated response.

The most common G3/4 toxicities were lymphopenia (32%), hyperglycemia (15%, unlikely related), thrombocytopenia (3%), and diarrhea (3%). No hospitalizations, opportunistic infections, or deaths occurred from CAPTEM.

The authors concluded that CAPTEM is an effective treatment for patients with progressive NET who failed high dose octreotide, with high PR and SD rates in carcinoids and insulinomas. The ongoing PFS in pancreatic NETs (>18.2 mo) is 150% greater than reported with everolimus and sutent.

The authors state “In this study, we’re seeing patients who had been given 6 months to live who are still alive 8 years after starting CAPTEM. The regimen was effective even in patients with tumours that hadn’t responded to any other standard treatment, including chemotherapy, high-dose octreotide, small molecule inhibitors, radiation or surgery.”

Source: Healio (medical news website)