Update on Adjuvant Chemotherapy Clifford Hudis, MD The impact of adjuvant chemotherapy is firmly established, but the optimal regimens and applications are still under development. Toxicity, rather than efficacy, was the theme at the 24th Annual San Antonio Breast Cancer Symposium. Cardiac Toxicity and Trastuzumab (Herceptin) The Eastern Cooperative Oncology Group presented results from a trial[1] evaluating a regimen of paclitaxel and trastuzumab followed by doxorubicin and cyclophosphamide (AC) and then randomization to additional trastuzumab or no further treatment. This study revealed that cardiac toxicity, while rare, is a potential issue as we broadly test trastuzumab in the adjuvant setting. Ongoing trials, including those of the Cancer and Leukemia Group B (CALGB), the National Surgical Adjuvant Breast and Bowel Project (NSABP), and the Breast Cancer International Research Group (BCIRG), will provide much-needed risk and benefit information in the coming years. Risk of Acute Leukemia With Conventional and Dose-Escalating Regimens: How Worried Should We Be? The NSABP, Pittsburgh, Pennsylvania,[2] reported that the risk of leukemia with AC using escalated doses of the alkylating agent was significantly increased but still low among 8563 patients followed for a median of 122 months; the risks of recurrence and death from breast cancer were significantly greater. On the other hand, given the lack of benefit for a 4-fold increase in dose and dose intensity for cyclophosphamide across their B22 and B25 trials, there is no compelling reason to use these regimens outside of clinical trials. Granulocyte colony-stimulating factor (G-CSF) was used routinely for doses of cyclophosphamide >/= 1200 mg/m2 x 4 in NSABP trial B25, which included patients with acute myeloid leukemia (AML), myelodysplastic syndrome, acute lymphoblastic leukemia, chronic lymphocytic leukemia, and chronic myeloid leukemia. The risk of AML seemed to increase with dose intensity, but only modestly and without statistical significance. Overall, the risk was 6-fold greater for the dose-intense regimens compared with the conventional regimen, but the 5-year cumulative risk was about 1.1% -- low, compared with the relapse rate in node-positive patients (35%). The risk of AML with regimens containing adjuvant epirubicin was estimated to be in the same range (1.5%) in a report from the National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario.[3] As regimens with increased efficacy are developed, even this level of risk will have to be reduced. Toxicity of Dose Escalation, Dose Dense Regimens, and the Use of Taxanes Randomized trials reported at this year's meeting suggest that dose escalation of CMF may allow for equal activity compared with AC[7] and that sequential epirubicin-paclitaxel-CMF may be no more toxic than the same regimen lacking the taxane.[8] In addition, phase 2 studies reported at this meeting suggest that dose-intense and dose-dense 5-fluorouracil-containing therapy (FAC) or AC with G-CSF support is active and feasible[9] and that sequential dose-dense epirubicin and paclitaxel may have an acceptable toxicity profile and warrant further study.[10] Taken together, the studies reported suggest that we have significant work ahead to demonstrate a convincing benefit for the taxanes while minimizing the overall toxicity of chemotherapy. The so-far unreported long-term results of many ongoing and completed randomized trials are awaited. Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.