Clinical Outcomes in Metastatic Gastroenteropancreatic Neuro-endocrine Tumors (NETs) with Temozolomide and Thalidomide Combination Therapy

Abstract

Purpose: Gastroenteropancreatic NeuroEndocrine Tumors (NETs) are heterogenous group of neoplasms which have limited response rates and significant toxicity with standard chemotherapy. Temozolomide is considered as a less toxic alternative for NETs. Combination with thalidomide is postulated to increase the efficacy by inhibiting the angiogenic pathways, but there is limited data available. Methods: The study was a retrospective study of patients with metastatic NETs, who received an oral thalidomide and temazolamide combination. Clinical data including patient's age, gender, race, type of cancer, previous therapies, clinical, radiological and tumor marker response to chemotherapy and toxicity was recorded. Results: The study group consisted of 12 patients with metastatic NETs, of which 5 were males and 7 females. The median age of diagnosis was 67 yrs (Range 47-79 yrs). Six patients had NET and 6 had carcinoid tumors. The primary sites of the tumor were pancreas ( n=4), small bowel (n=4), colon (n=2) and lung (n=2). The tumor markers secreted were as follows: chromogranin(n=10), serotonin (n=6), gastrin (n=2) and pancreatic polypeptide(n=1). The median chromogranin level at diagnosis was 47 Units/L (Range 5-122,000). Sites of metastases were liver (n=12), omentum (n=6), lungs (n=5) and bones (n=2). All patients had received sandostatin and received prior chemotherapy ranging from 1 to 3 regimens. Patients received a median of 1.5 (Range 1-9) cycles of temozolomide and thalidomide combination. Six patients came off thalidomide for toxicity and remained on temozolomide for another 4 cycles. Clinical, radiological and marker response could be evaluated in 8 patients; four patients were too early for response evaluation. Clinical best response was as follows: partial response (n=3), stable disease (n=4) and progression (n=1). Best radiographic response was as follows: partial response (n=2), stable disease (n=5) and disease progression (n=1). Tumor marker response was recorded as follows: partial response (n=2), stable disease (n=5) and progression (n=1). The reasons for discontinuation of regimen were toxicity (n=7) and disease progression (n=1). The most frequent treatment related adverse events were lymphopenia (n=4), abnormal LFTs (n=3), venous thromboembolism (n=2), peripheral neuropathy (n=2) and cardiomyopathy (n=1). Median survival was not obtained as 11 patients were still alive. Conclusion: The temozolomide and thalidomide combination regimen is effective in patients with metastatic NETs refractory to conventional chemotherapy and is worthy of further study. This regimen has treatable toxicities and patients should be monitored closely.