The somatostatin analog octreotide LAR (SandostatinR LARR) can retard tumor progression in patients with metastatic neuroendocrine midgut tumors, according to interim results of a phase IIIb trial reported here at the American Society of Clinical Oncology’s 2009 Gastrointestinal Cancers Symposium.

The study, conducted at 18 cancer centers in Germany, found that octreotide LAR was associated with a 66 percent reduction in the risk of disease progression compared with placebo after six months of treatment (p=0.000072).

“Octreotide LAR should be considered the standard of care in patients with newly diagnosed, functionally active or inactive, well-differentiated metastatic midgut neuroendocrine tumors and a low hepatic tumor load,” Rudolf Arnold, MD, with Philipps University in Marburg , Germany, said.

Dr. Arnold was the principal investigator of the trial, known as PROMID (Placebo-Controlled Prospective Randomized Study on the Antiproliferative Efficacy of Octreotide LAR in Patients with Metastatic Neuroendocrine Midgut Tumors).

He noted at a news conference that the standard treatment option for patients with metastatic midgut neuroendocrine tumors, a rare gastrointestinal tumor, is surgery. Additional options include hepatic embolization in the event of liver metastases or radioligand therapy. However, both approaches are associated with significant side effects, he added.

The trial included 85 treatment-naïve patients with histologically confirmed locally inoperable or metastasized well-differentiated neuroendocrine tumors and a Karnofsky index greater than 60.

About 70 percent of patients had surgery before enrolling in the trial to remove the primary tumor, while the remainder had more advanced, inoperable disease. Eighty six percent had liver metastases.

Participants were randomized to octreotide LAR 30 mg i.m. every four weeks or placebo i.m. every four weeks for 18 months or until CT- or MRI-documented tumor progression or death.

The primary endpoint was median time to tumor progression.

After six months of treatment, tumor progression was reduced in 69% of octreotide LAR-treated patients and 39% of placebo-treated patients, Dr. Arnold said.

The median time to tumor progression was 14.3 months in the octreotide LAR group and six months in the placebo group (HR=0.34, p=0.000072).

Importantly, octreotide LAR’s favorable effect was observed in patients with either functioning (hormone-secreting) or non-functioning (non-secreting) neuroendocrine tumors.

Patients who derived the most benefit were newly diagnosed patients who had a tumor load that was less than or equal to 10%, Dr. Arnold observed.

Because most patients enrolled in the trial are still alive, it is not yet possible to ascertain an overall survival benefit, he added.

The side effects related to octreotide LAR were in line with those reported in earlier studies of the drug in patients with neuroendroine tumors and included diarrhea, fatigue, fever, and bile stones. Five patients dropped out of the trial because of side effects.

“Overall, our results support the use of octreotide LAR for patients after cytoreductive surgery who have few remaining metastases,” Dr. Arnold said.

The PROMID trial is the first placebo-controlled study to test octreotide LAR for the treatment of malignant neuroendocrine tumors.

Octreotide has been used to treat the clinical syndromes associated with neuroendocrine tumors. Octreotide also substantially reduces and in many cases normalizes growth hormone and/or insulin-like growth (IGF) factor-1 levels in patients with acromegaly.

(Octreotide belongs to Novartis)

Written by Jill Stein
Jill Stein is a Paris-based freelance medical writer.
jillstein03(at)gmail.com