Editor’s Note

The promise of targeted systemic therapy

An interesting bout of community-acquired pneumonia in 1996 provided me with a very personal perspective on targeted systemic therapy. A couple of doses of Biaxin melted bilateral pulmonary infiltrates, and in 24 hours, I went from febrile immobility to a performance status of 90.

Interventions with antibiotic-like therapeutic ratios have long been sought in cancer medicine, and this issue of Breast Cancer Update provides encouraging evidence of significant progress in that direction. The three research leaders interviewed for our program were members of this year’s faculty at the 19th Annual Chemotherapy Foundation meeting in New York.* Virtually all of the sessions included presentations related to targeted treatment, and the research interests of our three speakers directly connect to this theme.

Edith Perez, principal investigator of the North Central Cancer Treatment Group’s Intergroup adjuvant trastuzumab trial, discusses encouraging preliminary unpublished evidence that the cardiotoxicity observed in the pivotal trials in metastatic disease has not yet been seen in the adjuvant setting — although she cautions that much longer follow-up is needed. She also reviews the challenges of quality control in both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) determinations of HER2 status — an increasingly common topic of journal articles and meeting presentations (Figure 1).

Robert Carlson discusses several key new developments in the oldest form of targeted therapy of breast cancer — endocrine treatment. His presentation in New York on the estrogen receptor downregulator, fulvestrant, included randomized trial data providing hints that this agent — which results in the disabling and disappearance of estrogen receptors — may have greater antitumor efficacy than another recent addition to the endocrine armamentarium, the third-generation aromatase inhibitor, anastrozole.

*To order the CD-ROM of this year’s program from Meetings by Mail®, visit the Chemotherapy Foundation Symposium page at the Mount Sinai School of Medicine website: www.mssmtv.org/tcf/

* = calculated, ACIS™= automated cellular imaging system, CTA = clinical trial assay (4D5 and CB11 antibodies)

The next issue of Breast Cancer Update will review new data — just presented at the San Antonio meeting — suggesting that after 15 years as the “gold standard” of adjuvant endocrine therapy, tamoxifen may soon be replaced by anastrozole (Figure 2).

At the Chemotherapy Foundation meeting, our third speaker, Dan Budman, presented some of the most elegant translational research data currently available in oncology. Dr Budman has chaired a number of key clinical trials in the long history of research on cytotoxic regimens in the adjuvant and advanced disease setting. In our interview, he noted with displeasure the empiric basis of selecting most available combination regimens.

In contrast, the new combination of capecitabine and docetaxel goes beyond the classic rationale of combining non-crossresistant regimens with different side effect profiles. Specifically, docetaxel upregulates thymidine phosphorylase, which in turn increases formation of 5-fluorouracil from capecitabine (Figure 3).

The ultimate goal of translational research is improved clinical outcome, and Dr Budman updates the results from a randomized trial comparing docetaxel to docetaxel/capecitabine. This landmark study continues to show a significant advantage to the combination in both response rate and survival. He also presents new quality of life data further supporting the docetaxel/capecitabine combination and notes that the key determinant of performance status in the metastatic setting is tumor control.

This first 2002 issue of our series also includes a few changes that reflect our interest in targeted education. Category 1 continuing medical education credit is now being provided; the format of this audio program supplement has been modified to improve utility; and our website, BreastCancerUpdate.com, now includes the full transcripts of the interviews.

Every oncologist who has cared for a patient as miserable as I was with a pulmonary infection, dreams about the day that antitumor therapy will destroy tumor cells the way a few antibiotic doses quickly wiped out the organisms in my lungs. Drs Perez, Carlson and Budman provide substantial evidence that we are making significant progress towards that elusive goal.

—Neil Love, MD

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