A duo of drugs, each targeting a prime survival strategy of tumors, can be safely administered and are potentially more effective than either drug alone for advanced, inoperable melanomas(黑素瘤) , according to a phase 1 clinical trial led by Dana-Farber Cancer Institute investigators2. The findings (abstract 8511), will be presented in an oral session at the annual meeting of the American Society of Clinical Oncology on Saturday, June 4, 3 p.m. CT, Arie Crown Theater, McCormick Place.
The drugs -- ipilimumab and bevacizumab -- are both monoclonal antibodies, intensified3 formulations of natural disease-fighting proteins. Ipilimumab spurs the immune system to attack diseased cells, including tumor1 cells. Bevacizumab, also known by the trade name Avastin, blocks the growth of blood vessels4 that provide tumors with nourishment5. Ipilimumab has extended the lives of metastatic melanoma patients in previous clinical trials, and bevacizumab is often used to treat tumors of the colon6, lung, and kidney.
The trial involved 22 patients with metatastic melanoma that was not treatable by surgery.
F. Stephen Hodi, MD, the study's lead author and director of the melanoma treatment center at Dana-Farber, said the trial is the first to explore whether the two agents enhance each other's effectiveness. Most of the participants didn't experience serious adverse7 side effects, although some did experience inflammation of artery8 walls, the liver, thyroid gland9, colon, or uvea(葡萄膜) (the middle layer of the eye). Five patients required steroid treatment for these problems and were removed the trial.
Positron emission10 tomography (PET正电子成像术) scans showed a prompt immune system response to many of the melanoma tumors, and computed11 tomography (CT) scans showed decreased blood flow to the tumors. Eight of the participants had partial responses -- showing some tumor shrinkage -- to the dual12 treatment, and six had stable disease. All the responses lasted at least six months. Biopsies performed after the treatment showed a more vigorous immune system response than would be expected with ipilimumab alone.
"Our findings indicate that ipilimumab and bevacizumab can be safely administered with careful management of side effects," said Hodi. "The results of lab tests suggest that the two agents may work synergistically(协同地) , with 14 of 21 evaluable patients experiencing a clinical benefit. This approach merits exploration in further clinical trials."