Phase II and Pharmacological Study of Oral Paclitaxel (Paxoral) Plus Ciclosporin in Anthracycline-Pretreated Metastatic Breast Cancer

cohort study do not allow us to draw definitive conclusions, the study certainly substantiates established data that report that functional status (ie, performance status) is more important than chronologic age.3-6 Therefore, a careful individual clinical assessment of older patients that takes into account any pre-existing comorbid conditions and assesses functional status will guide adjuvant recommendations. Hopefully, this data will continue to build the evidence that will collectively change our practices to achieve the best care for all patients, regardless of age. R. F. Swaby, MD L. J. Goldstein, MD

References 1. DeMichele A, Putt M, Zhang Y, et al: Older age predicts a decline in adjuvant chemotherapy recommendations for patients with breast carcinoma. Cancer 97:2150-2159, 2003. 2. Muss HB: Older age: Not a barrier to cancer treatment. N Engl J Med 345:1128-1129, 2001. 3. Muss HB, Woolf S, Berry D, et al: Adjuvant chemotherapy in older and younger women with lymph node-positive breast cancer. JAMA 293:1073-1081, 2005. 4. Langer CJ, Manola J, Bernardo P, et al: Cisplatin-based therapy for elderly patients with advanced non-small-cell cancer lung cancer: Implications of Eastern Cooperative Oncology Group 5592, a randomized trial. J Natl Cancer Inst 94:173-181, 2002. 5. Sweeney CJ, Zhu J, Sandler AB, et al: Outcome of patients with a performance status of 2 in Eastern Cooperative Oncology Group Study E1594: A phase II trial in patients with metastatic nonsmall cell lung carcinoma. Cancer 92:26392647, 2001. 6. Pepe C, Hasan B, Winton TL, et al: Adjuvant vinorelbine and cisplatin in elderly patients: National Cancer Institute of Canada and Intergroup Study JBR.10. J Clin Oncol 25:15531561, 2007.

Phase II Trial Evaluating the Palliative Benefit of SecondLine Zoledronic Acid in Breast Cancer Patients With Either a Skeletal-Related Event or Progressive Bone Metastases Despite First-Line Bisphosphonate Therapy Clemons MJ, Dranitsaris G, Ooi WS, et al J Clin Oncol 24:4895-4900, 2006 Most women with breast cancer metastases to bone receive monthly intravenous bisphosphonate therapy to delay the onset of SREs, such as new bone pain, fracture, or need for radiation therapy. There is little information or guidance on what we should do with the bisphosphonate therapy once an SRE occurs, with standard practice being to continue the same bisphosphonate therapy. This article presented a small phase II trial that attempted to address this

problem. Women who had an SRE or progressive bone metastases while on clondronate or pamidronate were switched to zoledronic acid, a third-generation bisphosphonate with higher antiresorptive activity. Measures of bone turnover and pain scores significantly decreased. Some of the limitations of this study were that the trial was small and the definition of progression for entry into the trial was somewhat vague. As well, the data needs confirmation in a larger phase III trial. The data in this trial, however, do hint that there may be differences in the clinical effect of bisphosphonates as second-line therapy, although a larger randomized trial in the firstline setting showed little difference.1 It would not be unreasonable, if cost and tolerability were not factors, to switch to zoledronic acid upon incidence of an SRE while receiving another bisphosphonate. A. M. Brufsky, MD, PhD

Reference 1. Rosen LS, Gordon D, Kaminski M, et al: Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: A phase III, double-blind, comparative trial. Cancer J 7:377-387, 2001.

Phase II and Pharmacological Study of Oral Paclitaxel (Paxoral) Plus Ciclosporin in Anthracycline-Pretreated Metastatic Breast Cancer Helgason HH, Kruijtzer CMF, Huitema ADR, et al Br J Cancer 95:794-800, 2006 This paper assessed the efficacy of oral paclitaxel plus ciclosporin (a P-glycoprotein inhibitor) in the treatment of metastatic breast cancer. Oral absorption of paclitaxel is poor because of its high affinity for membrane-bound P-glycoprotein. Thus administering paclitaxel with an inhibitor of P-glycoprotein would potentially increase its absorption. In this study, the response rate was 52%, and time to progression was approximately 6 months, with expected average survival. The drug caused mild myelosuppression and some nausea and vomiting, the latter because of the vehicle it was dissolved in, and the authors remarked that they had improved upon this for future-generation studies. This trial indicates that oral paclitaxel is at least as active as intravenous paclitaxel but probably no more active. The advantages of oral formulations include ease of administration; avoidance of cremophor, which can cause allergic reactions and other toxicities; greater flexibility in dosing and scheduling; and the ability to give it along with other oral agents in an all-oral combination. The disadvantages include potentially unpredictable systemic absorption due to diarrhea, nausea, or vomiting, and poor patient compliance. Overall, whereas this approach does not appear to offer any greater therapeutic efficacy, at least at this dosing schedule, it does allow for the possibility of increased flexibility in exploring dosing, scheduling, and administration issues in the future. R. M. Elledge, MD

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