A drug called Ban Zhi Lian, which is derived from a Chinese medicinal herb, received international attention in late 2007 when it was covered in Time Magazine.¹ Ban Zhi Lian (BZL101) is an aqueous extract from the aerial part of barbed skullcap (Scutellaria barbata, Lamiaceae). Developed by Bionovo, Inc. of Emeryville, California, BZL101 is being tested for use in breast cancer treatment.

This herbal preparation was used in a Phase I clinical trial in 2001 at Cancer Research Network in Plantation, Florida.¹ In this trial, 21 patients with stage 4 metastatic breast cancer took 12 grams a day of BZL101 for a year.^1,2 The results show that 4 of 16 patients (25%) had stabilization in their disease for 90 days, and 3 of 16 patients (19%) had stabilization for 180 days.^1,2,3 Five patients had objective tumor regression, including one patient who had a partial remission based on the study's modified response evaluation criteria in solid tumors (RECIST).

BZL101 appears to work by singling out tumor cells. The drug causes the cells to undergo apoptosis, programmed cell death, by preventing cancer cells from undergoing glycolysis, a process of glycogen breakdown responsible for 85% of the cell's energy.^1,2 From the Phase I trial, the investigators concluded that BZL101 had a favorable toxicity profile and recommended its further development for cancer treatment.

"There has been a shift in the standards of metastatic breast cancer treatment, as the oncology community moves to prescribing oral drugs at a lower toxicity, for both efficacy and quality of life reasons," wrote Mary Tagliaferri, MD, president, co-founder and chief medical officer of Bionovo (e-mail, December 6, 2007). "BZL101 would seem to fit this new standard as an oral drug designed from the outset for minimal side effects and proven favorable efficacy, even in a heavily pretreated patient population."

BZL101 is now undergoing a multi-center, Phase I & II, open-label, non-randomized, dose escalation trial to assess safety, feasibility, optimal dosing and preliminary efficacy at 9 clinical sites throughout the United States, according to Katherina Audley, director of corporate media and communications at Bionovo (e-mail, December 6, 2007) and Bionovo's Web site.³ The next trial is slated to enroll 80 women with breast cancer, 40 who are estrogen receptor positive (ER+) and 40 who are negative (ER-). For the meantime, however, the dose escalation portion of the study has been extended because of positive effects, according to a recent Bionovo press release.⁴

"We had expected to reach the maximum tolerated dose earlier, and then transition to the full Phase II component of the trial with that dose. Instead, we have seen very favorable tolerability data at the higher doses, and we are continuing to escalate the dose," said Dr. Tagliaferri.⁴ "As a result of this positive news, we will continue the dose escalation, so long as we continue to see favorable tolerability and safety, after which we will transition to the full Phase II study component."

In general medical research, Phase I clinical trials address the safety and tolerability of a drug and determine the maximum tolerated dose or the appropriate biological active dose. Phase II clinical trials focus on determining a drug's efficacy; however, in cancer research Phase I trials can also measure efficacy as an outcome in a descriptive fashion.

According to Charlotte Gyllenhaal, PhD, research assistant professor at the University of Illinois at Chicago and associate editor of Integrative Cancer Therapies (a peer-reviewed journal dealing with non-conventional cancer treatments): "It is certainly a breakthrough in cancer research for a company to be testing an herbal extract for its cancer treatment properties, since herbs may eventually turn out to be easier to tolerate than pure compound anticancer drugs. This is a breakthrough that was made possible by the FDA's new Botanical Drug classification, and it is great to see that in action in the cancer area" (e-mail, December 5, 2007). Dr. Gyllenhaal is referring to the FDA guidance document that establishes FDA policy in addressing botanicals as drugs in the United States.⁵

Dr. Gyllenhaal is a member of the American Botanical Council Advisory Board. More information about BZL101 is available on the Web at www.bzl101.com and www.bionovo.com.