B细胞受体抑制物可缓解淋巴球性白血病

A new, targeted approach to treating chronic¹ lymphocytic leukemia（淋巴球性白血病） has produced durable² remissions in a Phase I/II clinical trial for patients with relapsed or resistant³ disease, investigators⁵ report at the 53rd Annual Meeting of the American Society of Hematology. "PCI-32765, one of a new class of experimental drugs called B cell receptor inhibitors, has shown impressive potential in this clinical trial for its effectiveness and particularly for its relatively⁶ minimal⁷ toxicity," said lead investigator⁴ Susan O'Brien, M.D., professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center.

According to the National Cancer Institute's Surveillance Epidemiology and End Results database, an estimated 14,570 people will receive a diagnosis⁸ of CLL in 2011 and about 4,380 patients will die of the disease.

Six-month progression free survival of 90-92 percent

Of 27 CLL patients treated at a dose of 420 milligrams daily, 70 percent had complete or partial remission（缓解，宽恕） at 10.2 months of median follow-up. Six-month progression-free survival was 92 percent. Patients received a median three prior treatments before entering the clinical trial.

At a higher dose of 840 mg, 44 percent of 34 patients achieved complete or partial remission at 6.5 months median follow-up, similar to the response rate of the lower-dose cohort at 6.2 months. Progression free survival at 6 months was 90 percent. Study participants had received a median（中值） of five prior treatments.

Overall, five patients (8 percent) of the 61 from both arms had progressive disease and 50 (82 percent) remained on the therapy.

Drug does not suppress blood cell production

CLL presently is treated with combination chemotherapies that can cause myelosuppression -- inhibited⁹ bone marrow¹⁰ function leading to decreased production of blood cells. The resulting susceptibility to infection can be a problem for patients, O'Brien said.

"PCI-32765 is not myelosuppressive. The main side effect is mild diarrhea（腹泻，痢疾） that is usually self-limiting," O'Brien said.

Chronic lymphocytic leukemia is caused by overproduction of defective¹¹ B cell lymphocytes, white blood cells that fight infection by producing antibodies.

PCI-32765 is orally administered and inhibits¹² the Burton's tyrosine kinas (BT) enzyme¹³, which is central to B cell receptor signaling. The drug causes programmed cell death and hinders cell migration¹⁴ and adhesion（粘附，支持） in malignant¹⁵ B cells.

A Phase III clinical trial is planned. The clinical trial was funded by Pharmacyclics, Inc., the drug's developer.

Study co-investigators with O'Brien are: Jan Burger, M.D., Ph.D., also of MD Anderson's Department of Leukemia; Kristie Blum, M.D., Amy Johnson, Ph.D., Nyla Heerema, Ph.D., and John Byrd, M.D., of The Ohio State University; Richard Furman, M.D., of Weill Cornell Medical College; Steven Coutre, M.D., of Stanford Cancer Center, Stanford University School of Medicine; Jeff Sharman, M.D., of U.S. Oncology; Ian Flinn, M.D., Ph.D., of Sarah Cannon¹⁶ Research Institute, Nashville, TN; Barbara Grant, M.D., Vermont Cancer Center, University of Vermont, and Tasheda Navarro, Eric Holmgren, Ph.D., and Eric Hedrick, M.D., all of Pharmacyclics, Inc.