ASCO 2013: Weekly Paclitaxel Is Less Toxic but as Effective for Women with Higher-risk Early-stage Breast Cancer
Low-dose weekly administration of paclitaxel resulted in equal progression-free survival but reduced overall toxicity compared to every-2-week dose-dense administration for women with higher-risk early-stage breast cancer who have undergone surgery, according to a phase III randomized trial.
“Our results suggest that either regimen will give a good outcome, but the weekly schedule seems to result in better quality of life for patients, causing less muscle and bone pain and allergic reactions,” said lead study author G. Thomas Budd, MD, a medical oncologist at the Cleveland Clinic in Cleveland, Ohio, at the 2013 ASCO Annual Meeting (Abstract CRA1008). “The findings provide assurance that women can choose the lower-dose therapy without sacrificing their chances of survival.”
Both the weekly and every-2-week schedule for administering paclitaxel are widely used in practice, but until this study, there had not been a formal comparison of their efficacies.
“The current trial demonstrates that weekly paclitaxel dosing and every-2-week dosing were equally effective in preventing breast cancer progression. However, weekly dosing caused less toxicity, and should ultimately be associated with lower cost due to less use of granulocyte colony-stimulating factor,” remarked Andrew D. Seidman, MD, Attending Physician for the Breast Cancer Medicine Service at Memorial Sloan-Kettering Cancer Center, New York. “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.”
Progression-free Survival Exceeds 80%
The trial accrued a total of 3,294 patients with node-positive or high-risk node-negative operable breast cancer. This study was originally a four-arm study, but after November 2010, it became a two-arm study, with all patients receiving doxorubicin at 60 mg/m2 and cyclophosphamide at 600 mg/m2 every 2 weeks, with either paclitaxel at 175 mg/m2 with pegfilgrastim (Neulasta) support every 2 weeks for 6 cycles, or paclitaxel at 80 mg/m2 per week for 12 cycles.
The estimated 5-year progression-free survival rates were equivalent: 82% for weekly and 81% for every-2-week paclitaxel. “It appears from these data that either way of giving the paclitaxel produces similar outcomes, so in terms of outcome, a doctor and a patient could choose either one of these two schedules,” Dr. Budd said.
Type and Severity of Side Effects
“Overall, about a third of the patients had significant—that is, grade 3 or 4—toxicity,” Dr. Budd stated. The every 2 week schedule was associated with higher frequency of grade 3/4 allergic reactions (1.4% vs 0.6%) and musculoskeletal pain (11% vs 3%). The frequency of neurologic toxicity was also higher in the every 2 week regimen (17% vs 10%), but the magnitude of the difference could be due to patients receiving six cycles of the every 2 weeks treatment rather than four cycles, which is current practice. Six cycles of the every 2 weeks regimen was selected in this study so that patients in both arms would be on treatment for 12 weeks.
Hematologic side effects were greater with the weekly schedule (17% vs 6%), but there may have been “an ascertainment bias,” Dr. Budd noted, “Patients getting treatment weekly have their blood counts checked weekly, so we looked more often, so there is more of an ascertainment bias.” In addition, since patients getting dose-dense treatment also received hematopoietic growth factors to boost the white cells, “that may have reduced the rate in which we detected a low white count.” Dr. Budd also noted that there were no differences in the rates of infectious complications between patients receiving and not receiving hematopoietic growth factors.
Some side effects resolve by themselves; others do not. “The muscle pain is transient but often requires treatment. The neuropathy usually resolves, but it takes months and months—6 months to a year. In some patients, it does not resolve. It improves, but it does not resolve,” Dr. Budd said.
“The significant bone pain that can sometimes occur from the growth factors would not be a consideration for lower weekly dose of paclitaxel, which does not generally require growth factor support,” Dr. Seidman added.
Weekly Dosing May Lower Costs
“These data suggest to me that we can get the same benefit with less toxicity, possibly with less cost,” Dr. Seidman said. While the cost of growth factor support was not addressed in this study, it “is not trivial,” he noted.
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.
This research was supported in part by the National Cancer Institute and Amgen, Inc. Dr. Budd reported a consultant or advisory role with Amgen.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
