There are few hard and fast rules for the medical treatment of patients with metastatic pancreatic neuroendocrine tumors. Two agents which have shown promise include everolimus (Afinitor – Novartis) and temozolomide (Temodar ~ Merck).
An article by Kulke and colleagues at Harvard Medical School and the associated Dana-Farber Cancer Institute in Boston as published in the June 3rd edition of the journal Cancer offers the results of a phase I/II clinical trial for a regimen consisting of a combination of the drug agents everolimus and temozolomide for the treatment of advanced neuroendocrine tumors.
In this study, 43 patients with diagnosed metastatic neuroendocrine tumors were given this regimen in two cohorts, and with an escalation of temozolomide dosage after safeties were observed. The progression-free survival median for patients was found to be 15.4 months. The overall median survival point was not reached. The temozolomide treatment was limited to a total duration of six months.
The authors suggest that the toxicity profile appeared to be reasonable. And thus, with apparent activity and tolerable side-effects, the everolimus and temozolomide combination may be appropriate for the treatment of advanced neuroendocrine tumors, and certainly merits further investigation including trying to discover whether the regimen improves survival over the use of each agent alone.
Dale O’Brien, MD
One of the great pleasures of doing worldwide reviews of the medical literature on pancreatic cancer is encountering the obscure, deep background, early and even unusual research on the topic. The following study must fit into one or more of these categories, I think.
Nishino and colleagues of the College of Pharmacy and Pharmaceutical Sciences at Howard University in Washington, DC published recent research in The Journal of Complementary and Integrative Medicine that looked at the administration and effects of the extract of red beets (Beta vulgaris L. – one of the main kinds that we prepare and eat) coupled with the chemotherapy drug doxorubicin on various human cancer cell lines including that of pancreatic cancer.
They found that this combination (beet plus doxorubicin) provided synergy in toxicity against the pancreatic cancer cells.
This is interesting early work that is perhaps deserving of further exploration.
Dale O’Brien, MD
The issue of offering combination treatment with radiation and chemotherapy AFTER pancreatic cancer surgery to improve survival had been in place based on the August 1985 classic study by the (U.S.) Gastrointestinal Tumor Study Group under Kalser and Ellenberg published in the Archives of Surgery. This appeared to have been confirmed by European researchers, but the additional use of the radiation in the regimen has been strongly challenged by the work of the European Study Group for Pancreatic Cancer since the early 1990s.
This debate has raged on – with research appearing to support each side at different times.
A recent article by Landry and colleagues at Emory University in Atlanta may help shed some light on the subject. In the June 15th issue of the journal Cancer, the authors report reviewing National Cancer Data Bank information from 1998 until 2002 – specifically looking for the outcomes of the treatment of pancreatic cancer in those treated with surgery and subsequent adjuvant (added) radiochemotherapy – as broken out by the dosage used in the radiation portion of the regimen.
The researchers looked at four radiation dosage categories – and found that those who received more than OR less than the perceived optimal (and in this case actual optimal) dosage of radiation, did not fare as well as those who received the optimal dose (between 50 to 55 Gy – gray units).
This is an intriguing finding – which could help explain apparent disparate results among serious scientists
The results are preliminary, and deserve further inquiry to help determine the extent of adjuvant treatment that is generally necessary to produce the best outcomes after the surgery for pancreatic cancer.
Dale O’Brien, MD