| General information |
| Database: | DB00900 |
| Objective: | Both everolimus and temozolomide are associated with singleagent activity in patients with pancreatic neuroendocrine tumor (NET). a phase 1/2 study was performed to evaluate the safety and efficacy of temozolomide in combination with everolimus in patients who have advanced pancreatic NET. |
| Authors: | Chan JA, et al |
| Title: | A prospective, phase 1/2 study of everolimus and temozolomide in patients with advanced pancreatic neuroendocrine tumor. |
| Journal: | Cancer. |
| Year: | 2013 |
| PMID: | 23733618 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | everolimus and temozolomide
|
| Target: | NA
|
| Cancer Type: | pancreatic cancer |
| Cancer Subtype: | advanced pancreatic neuroendocrine tumor |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | everolimus+temozolomide |
| Study Type: | A prospective, phase I/II study |
| Key Patients Feature: | patients were required to have histologically confirmed low or intermediate grade (G1 and G2) metastatic or locally unresectable pancreatic NET. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | patients were treated with temozolomide at a dose of 150 mg/m(2) per day on days 1 through 7 and days 15 through 21 in combination with everolimus daily in each 28day cycle. In cohort 1, temozolomide was administered together with everolimus at 5 mg daily. Following demonstration of safety in this cohort, subsequent patients in cohort 2 were treated with temozolomide plus everolimus at 10 mg daily. The duration of temozolomide treatment was limited to 6 months. |
| Primary End Point: | toxicity, radiologic and biochemical response, and survival |
| Secondary End Point: | NA |
| Patients Number: | 43 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 40% |
| Disease Control Rate: | 93% |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 15.4 months (95% CI, 9.4-20.4 months) months |
| Median OS A vs. C: | NR(not reached) |
| Adverse Event(agent arm): | Nearly half (44%) of patients experienced grade 3 or 4 lymphopenia, and 16% experienced grade 3 or 4 thrombocytopenia. Other common toxicities included mild mucositis, hyperglycemia, hypercholesterolemia, hypertriglyceridemia. |
| Conclusions: | Temozolomide and everolimus can be safely administered together in patients with advanced pancreatic NET, and the combination is associated with encouraging antitumor activity. Future studies evaluating the efficacy of combination therapy compared to treatment with either agent alone are warranted. |