Weekly chemo effective in IBC

watergirl

I did weekly chemo at UW so I try to keep up with the latest reports of its effectiveness.  They recently put out some interium results and it shows it has one of the highest pCR (~30%) rates reported for IBC.   Pathologically complete response (pCR) of 30% means that the 30% women of the women who had tumors prior to chemo showed NED at the time of surgery (which followed chemo). 

This is from http://www.clinicalbreastcancer.com/publication/caas_v7n11/article1.php

Q: Results from a Southwest Oncology Group trial (SWOG 0012) suggest neoadjuvant therapy with weekly doxorubicin and daily cyclophosphamide followed by weekly paclitaxel with growth factor support was tolerable and improved pathologic CRs (pCRs) when compared to a regimen in which the anthracycline/cyclophosphamide portion was administered every 3 weeks. Would you consider using metronomic therapy in the neoadjuvant or metastatic setting?

Dr. Rugo: SWOG 0012 was a precursor for an ongoing adjuvant trial (SWOG 0221) that is looking at a novel approach to the administration of chemotherapy based on previous studies showing that metronomic dosing can overcome chemotherapy resistance in a variety of model systems.11 A pilot trial evaluated dose-dense anthracycline-based chemotherapy in women with node-positive breast cancer and showed a very impressive 5-year eventfree survival of 86% in women who had a median of 4 positive nodes.12 SWOG 0012 compared standard chemotherapy to the metronomic approach in the neoadjuvant setting.13 The primary endpoint was pCR. A total of 372 patients with LABC or infl ammatory breast cancer (IBC) were enrolled in the study, with 265 evaluable for primary outcome. Metronomic chemotherapy consisted of doxorubicin 24 mg/m2/week and oral cyclophosphamide 60 mg/m2/day for 15 weeks, with weekly granulocyte colony-stimulating factor (G-CSF) support. In previous trials, patients who did not receive growth factors had an increase in dermatitis as well as hematologic toxicity, which was ameliorated with G-CSF support. The control arm received every-3-week doxorubicin/cyclophosphamide at standard doses for 5 doses (as opposed to the standard 4). Both treatment groups then received standard weekly paclitaxel for 12 weeks. Approximately 30% of the patients had IBC, so this was a very locally advanced disease group. The toxicity between the arms was similar to that seen in prior studies (13% grade 3/4 hand-foot syndrome [HFS] associated with metronomic dosing vs. 0 with standard treatment), but neutropenia was markedly reduced because of the G-CSF (16% with metronomic dosing vs. 47% with standard treatment). There was very minimal difference in reports of febrile neutropenia.

The response results are quite striking. There was a statistically significant difference in pCR rate at the primary site of 19% in the standard arm compared to 31% in the metronomic arm. This is one of the highest pCR rates reported in IBC. Considering patients who had both pCR and node negativity, the difference is also striking: 15% in the standard arm compared to 26% with metronomic-dose chemotherapy. The metronomic regimen is clearly quite tolerable, HFS being the major toxicity, with fewer hematologic side effects and what appears to be improved efficacy compared to standard dosing. This study demonstrates that occasionally data from preclinical models can inform the clinical setting with very positive results. The very encouraging clinical results support enrollment to SWOG 0221, an ongoing adjuvant trial comparing dose-dense chemotherapy to the metronomic approach. I would strongly encourage people to consider enrolling in this trial, particularly those with high-risk, node-positive disease.

Should we be using metronomic-dose chemotherapy as standard treatment for patients? Not yet. We don't yet know how this fits into our treatment armamentarium. However, when we don't really know the right treatment for a patient with IBC, providing that the patient does not have HER2-overexpressing disease, I think that following the regimen presented in SWOG 0012 is a reasonable approach because it is very well tolerated and potentially results in improved response. Further data regarding this treatment approach will be obtained from SWOG 0221.