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Other highlights in the April 8 JNCI
Date:4/8/2008

Randomized Clinical Trial Results on Preoperative Chemotherapy in Early Breast Cancer

Eight cycles of preoperative chemotherapy was no better than six cycles in women with early breast cancer who had responded to two initial cycles, according to data from a randomized controlled trial. Additionally, women who failed to respond to the first two cycles of one drug combination did not benefit from switching to a different drug combination for four additional cycles, compared with those who continued receiving the original combination for four more cycles.

Preoperative chemotherapy, also known as neoadjuvant chemotherapy, is used to shrink the tumor to improve surgical options and provide early information about a patient's response to treatment.

In a randomized controlled trial, Gunter von Minckwitz, M.D., of the Universitäts-Frauenklinik in Frankfurt and colleagues in the German Breast Group treated 2,090 women with two cycles of preoperative docetaxel, doxorubicin, and cyclophosphamide (TAC). The researchers then randomly assigned the 1,390 women whose tumors responded to therapy to either four or six additional cycles of TAC. The proportion of women who had a complete pathological response was similar in the two arms—21 percent and 23.5 percent, respectively.

The 622 women who failed to respond to the initial two cycles of TAC were randomly assigned to either four additional cycles of TAC or four cycles of capecitabine plus vinorelbine (NX). Increasing the number of TAC cycles or switching regimens did not appear to improve outcomes. Only 5.3 percent of women on TAC achieved a complete pathological response and 6.0 percent of the women on NX.

In an accompanying editorial, Francisco J. Esteva, M.D., Ph.D., and Gabriel N. Hortobagyi, M.D., of the University of Texas M. D. Anderson Cancer Center in Houston review the results of the German trial and other trials that tested neoadjuvant therapy. The data indicate that neoadjuvant therapy is effective and that the full benefit can be achieved with a limited number of treatment cycles. Not all women benefit equally though, and therefore new treatment approaches are needed.

"Patients who do not respond to the initial chemotherapy should be considered for alternative treatment approaches, if possible as part of a clinical trial," the editorialists write.

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Frequent Blood Donation Unrelated to Donors' Risk of Cancers

Frequent blood donation does not change an individual's risk of developing cancer.

While iron is a vital trace element for essentially all living organisms, too much iron has been implicated as a possible risk factor for certain cancers. If true, blood letting might be protective. On the other hand, blood cell proliferation after donation might increase the risk of malignancy. The interpretation of previous studies has been complicated by the fact that blood donors have a healthier lifestyle than most comparison groups. Therefore, blood donors should ideally be compared with other blood donors.

Gustaf Edgren, Ph.D., of the Karolinska Institute in Stockholm and colleagues performed a case-control study within a larger group of Swedish and Danish blood donors. They compared the frequency of donations among 10,866 regular blood donors who developed malignancies with the frequency of donations among 107,104 regular donors who did not.

They found no clear trend for an increased or decreased risk of cancer with increased donations. "In conclusion, we found that repeated blood donation was not associated with risk of cancer overall," the authors write.

Contact: Gustaf Edgren, gustaf.edgren@ki.se, +46 708 18 68 62 (mobile) or +46 8 524 861 40


Novel Mechanism to Overcome Resistance to Targeted Therapy Identified

Combining ABT-737, a molecularly targeted drug that promotes programmed cell death, with a second agent that induces metabolic stress increases acute lymphoblastic leukemia (ALL) cell death in vitro and overcomes resistance to single-agent ABT-737 treatment.

ABT-737 inhibits Bcl-2, a pro-survival protein that is overexpressed in many tumor types. Drugs that increase the production of reactive oxygen species, such as 4-HPR [N-(4-hydroxyphenyl)retinamide], increase metabolic stress and promote programmed cell death.

To find out if combining ABT-737 and 4-HPR would improve the anti-cancer activity of ABT-737, Min H. Kang, Pharm.D., of the University of Southern California Children's Hospital Los Angeles tested the drugs in seven human ALL cell lines. Two of the lines tested were resistant to single-agent ABT-737 therapy.

The addition of 4-HPR increased cell death in all lines tested, compared with treatment with either single agent alone. Treating cells with 4-HPR reduced expression of a cellular protein, Mcl-1, and decreased cell signaling activity, which helped overcome resistance to ABT-737 treatment.

"The inhibition of Mcl-1 expression by 4-HPR is a novel observation, and the inhibition of Mcl-1 expression is likely to underlie, at least in part, the synergistic cytotoxicity between ABT-737 and 4-HPR in ALL cell lines," the authors write.

Contact: Min Kang, mkang@chla.usc.edu, (323) 361-8724

Also in April 8 JNCI:


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Contact: Liz Savage
jncimedia@oxfordjournals.org
301-841-1287
Journal of the National Cancer Institute
Source:Eurekalert

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