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What Is the Best Chemotherapy Treatment Option for Anthracycline and Taxane Pretreated Metastatic Breast Cancer?

Sunnybrook and Women’s Health Sciences Centre Toronto, Ontario, Canada

Anil A. Joy, John R. MacKey

Cross Cancer Institute, Edmonton, Alberta, Canada

To the Editor:

We commend Keller et al for their study evaluating pegylated liposomal doxorubicin (PLD) versus vinorelbine or mitomycin C plus vinblastine in women with taxane-refractory advanced breast cancer.¹

With the increasing use of anthracyclines and taxanes in the adjuvant and first-line metastatic settings, there is a need for effective therapeutic agents for this patient population on disease progression. Commonly used agents include capecitabine, vinorelbine, gemcitabine, and PLD. Unfortunately, there are few randomized trials in the literature comparing the efficacy of these agents against one another in patients with disease that would be considered anthracycline and taxane refractory.

Keller et al have performed a well-designed clinical trial to help answer the question as to which chemotherapy treatment option is the most appropriate for this particular patient population. They conclude that PLD is comparable in efficacy to vinorelbine or mitomycin C plus vinblastine, with a superior toxicity profile. However, overall survival remains poor with no statistical difference between PLD and the comparator arms (10.4 months v < 9.0 months respectively, p < = NS).

The Keller study has limited practical application as it fails to incorporate another effective agent, capecitabine, a current standard option for this anthracycline and taxane refractory population. Capecitabine, an oral fluorouracil prodrug, has significant activity in metastatic breast cancer (MBC) with reported response rates in taxane-refractory metastatic breast cancer of 20%.² There are also two small, phase IIB studies in the first-line setting (intravenous cyclophosphamide, methotrexate, fluorouracil v < capecitabine, and paclitaxel v < capecitabine); both favor capecitabine. ^3,4

Given the lack of trials comparing vinorelbine with capecitabine, we conducted a retrospective review at two large Canadian cancer centers to evaluate the efficacy of capecitabine, vinorelbine, or both agents sequentially in anthracycline and taxane refractory MBC.⁵ One hundred forty-one patients met study inclusion criteria: 45 patients received single agent vinorelbine, 68 patients received single agent capecitabine, and 28 patients received combined sequential therapy. The mean duration of therapy was 2.3 months with vinorelbine and 4.6 months with the capecitabine treatment group. Median overall survival time was 3.4 months for the vinorelbine group and 6.3 months for capecitabine group (P <.0001). Of the twenty-eight patients who received both agents in sequence, the mean duration of therapy was 3.9 months (3.1 months with vinorelbine followed by capecitabine and 4.9 months with capecitabine followed by vinorelbine), with a median overall survival of 13 months. Survival at 1 year was 15.6% for the vinorelbine group, 28.4% for the capecitabine group, and 46.4% for the sequential group (P < =.017).

Our study supports Keller's observation that patients who have anthracycline and taxane refractory MBC may derive palliative survival benefit from additional chemotherapy. In our retrospective review women who received capecitabine appeared to survive longer than those who received vinorelbine alone. Until randomized comparative studies are available to directly evaluate the relative efficacy of these agents, we suggest that the potential benefits of capecitabine chemotherapy in taxane and anthracycline pre-exposed patients should not be underestimated.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Keller AM, Mennel RG, Georgoulias VA, et al: Randomized Phase III Trial of Pegylated Liposomal Doxorubicin Versus Vinorelbine or Mitomycin C Plus Vinblastine in Women With Taxane-Refractory Advanced Breast Cancer. J Clin Oncol 22:3893-3901, 2004[Abstract/Free Full Text]

2. Blum JL, Jones SE, Buzdar AU, et al: Multicenter Phase II Study of Capecitabine in Paclitaxel-Refractory Metastatic Breast Cancer. J Clin Oncol 17:485-493, 1999[Abstract/Free Full Text]

3. O'Shaughnessy JA, Blum J, Moiseyenko V, et al: Randomized, open-label, phase II trial of oral capecitabine (Xeloda) vs. a reference arm of intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) as first-line therapy for advanced/metastatic breast cancer. Ann Oncol 12:1247-1254, 2001[Abstract/Free Full Text]

4. Talbot DC, Moiseyenko V, Van Belle S, et al: Randomised, phase II trial comparing oral capecitabine (Xeloda) with paclitaxel in patients with metastatic/advanced breast cancer pretreated with anthracyclines. Br J Cancer 86:1367-1372, 2002[CrossRef][Medline]

5. Verma S, Trudeau M, Dranitsaris G, et al: Survival differences observed in anthracycline and taxane refractory metastatic breast cancer treated with capecitabine when compared to vinorelbine. Breast Cancer Res Treat 88:s201, 2004 (suppl 1, abstr 5050)

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• In Reply:
  Alan M. Keller
  JCO 2005 23: 6261 [Full Text]

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