Results from a recent, phase III, randomized clinical trial, supported, in part, the National Cancer Institute and Amgen, shows thatlow-dose weekly administration ofadjuvant paclitaxel (Taxol?, Bristol-Myers Squibb Company) vs.standard,every two weeks administrationin women withhigher-risk early-stage breast cancer who have undergone surgery yieldsequal progression-free survival (PFS). However, the researchers also found thatcertain side effects were more common with the every two weeks regimen. This, according to the researchers, suggests the weekly schedule may be preferable.The study results were presented at the 49th Annual Meeting of theAmerican Society of Clinical Oncology(ASCO), being held in Chicago, Il, May 31 – June 4, 2013.

These study’s practice changing findings may lead to more doctors utilizing the weekly schedule, which could also result in cost savings, as the every two weeks regimen requires additional supportive care, including growth factors (e.g., pegfilgrastim; Neulasta?, Amgen) to boost white blood cell production.

A Phase III study shows that a weekly regimen of adjuvant paclitaxel chemotherapy for women with early-stage breast cancer was comparable to the standard, biweekly regimen, but caused substantially fewer side effects.

Paclitaxel,a compound that is extracted from the bark of the Pacific yew tree,is a long-standing component of breast cancer treatment. The drug is typically given to patients either weekly or every two weeks, at a higher dose. Both approaches are widely used in practice but until this study, there has not been a formal comparison of their efficacies.

In December of 1992, theU.S. Food and Drug Administration (FDA)approved paclitaxelfor treatment of ovarian cancer that had not responded to standard chemotherapy.Subsequent clinical trials demonstrated that paclitaxelwas also effective in treating advanced breast cancer and in april 1994, theFDAapproved the drug for the treatment of metastatic breast cancer that did not respond to combination chemotherapy, or breast cancer that had recurred within six months after the completion of initial chemotherapy.Paclitaxel is alsoapproved for adjuvant treatment of breast cancer that has spread to the lymph nodes when given following a doxorubicin chemotherapy regimen.

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Weekly schedule offer better QoL
?Our results suggest that either regimen will give a good outcome, but the weekly schedule seems to result in better quality of life (QoL) for patients, causing less muscle and bone pain and allergic reactions,? noted lead study author G. Thomas Budd, MD, a medical oncologist andstaff physician in the Taussig Cancer Center at the Cleveland Clinicin Cleveland, Ohio. ?The findings provide assurance that women can choose the lower-dose therapy without sacrificing their chances of survival.?

In this trial, patients with node-positive or high-risk node-negative operable breast cancer first received treatment with one of three different regimens of doxorubicin and cyclophosphamide and then received one of two different regimens of paclitaxel, in a randomized fashion. The paclitaxel regimens studied were:

  • a standard-dose treatment given every two weeks for 12 weeks with pegfilgrastim support, or
  • a low-dose weekly regimen for12 weeks.

The results of the doxorubicin and cyclophosphamide treatment were reported at ASCO in 2011, and the results of a comparison of the two ways of giving paclitaxel were reported today.

The estimated five-year progression-free survival (PFS) rates for weekly and every two weeks paclitaxel were equivalent ? 82% and 81% respectively. The two schedules differed in the type and severity of side effects: the every two week schedule was associated with higher frequency of allergic reactions (1.4% vs. 0.6%), and muscle and bone pain (11% vs. 3%), compared to the weekly schedule. The frequency of neurologic toxicity, a common side effect involving numbness, tingling and pain of the fingers and toes, was also higher in the every two week regimen (17% vs. 10%), but this difference may have been smaller had the patients received only four cycles of every two weeks therapy (as is current practice) rather than six. (Six cycles of every two weeks regimen was selected in this study so that patients in both arms would be on treatment for 12 weeks).

Preventing breast cancer progression
?The current trial demonstrates that weekly paclitaxel dosing and every two weeks dosing were equally effective in preventing breast cancer progression. However, weekly dosupportedsing caused less toxicity, and should ultimately be associated with lower cost due to less use of granulocyte colony stimulating factor. While some oncologists have already been using the weekly schedule for adjuvant therapy, these results will motivate many doctors, including myself, to use weekly dosing,? said Andrew D. Seidman, MD, ASCO spokesperson and breast cancer expert.

A longer follow-up of patients enrolled in this study is planned, in addition to several ancillary studies using participants? tumor samples. Those studies will explore genetic factors that predict the likelihood of toxic side effects in individual patients treated with paclitaxel and effects of diet and exercise on treatment efficacy and side effects.

For more information:
Abstract #CRA1008: S0221: Comparison of two schedules of paclitaxel as adjuvant therapy for breast cancer.
Authors: Budd GT, Barlow WE, Moore HCF, Hobday TJ, Stewart JA, Isaacs C, Salim M, et al.
Oral Abstract Session: Breast Cancer ? Triple-Negative/Cytotoxics/Local Therapy
Date: Monday, June 3, 2013, 12:15 ? 12:30 PM CDT
Location: Room: N Hall B1
Reference:J Clin Oncol 31, 2013 (suppl; abstr CRA1008)

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