Weekly Taxol and carboplatin for breast cancer – pro

Two independent phase II studies have shown that the combination of carboplatin and docetaxel (Taxotere®; Aventis Pharmaceuticals, Inc.; Bridgewater, NJ) is active in the first-line treatment of metastatic breast cancer. Based on these promising results, nonanthracycline alternatives were investigated, with many of them incorporating platinum agents.

The benefit of adding carboplatin to paclitaxel and trastuzumab in the first-line treatment of HER2-overexpressing metastatic breast cancer was further shown in results from an ongoing phase III study. Updated data indicate that the group receiving carboplatin had a significantly higher response rate (52% versus 36%, p = 0.03) and a longer median time to progression (10.3 versus 7.0 months, p = 0.016) than the group receiving only paclitaxel and trastuzumab.

A recent review concluded: “In several phase II studies, combination carboplatin and paclitaxel (Taxol®; Bristol-Myers Squibb) therapy was active and reasonably well tolerated in the first-line treatment of metastatic breast cancer, producing objective response rates of 53%–62%—substantially higher rates than those seen in other phase II trials of either drug alone. Similar phase II data for carboplatin with docetaxel (Taxotere®; Aventis; Bridgewater, NJ) have been reported, and recent phase III data suggest that adding carboplatin to a paclitaxel/trastuzumab regimen produces superior efficacy than paclitaxel/trastuzumab alone for patients with HER2+ metastatic disease. Drug scheduling plays an important role in the therapeutic ratio of this combination treatment.”

To amplify, weekly administration of paclitaxel is active in patients with metastatic breast cancer, including patients treated previously in the adjuvant or metastatic setting, and produces a mild toxicity profile In one study of 95 evaluable patients, eight (8%) had complete responses and 51 (54%) had partial responses for an overall response rate of 62%. The response rates did not differ between those receiving the 135 mg/m2 paclitaxel dose and those receiving the 100 mg/m2 dose. The median time to progression, however, was somewhat shorter than that observed with the q3w schedule. A phase III trial would be required to avoid the inherent difficulties of comparing data across phase II studies with different treatment regimens. Such a study has not been done.

FDA status:

•TAXOTERE (docetaxel for injection) is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy.
•TAXOTERE (docetaxel for injection) in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with operable node-positive breast cancer.
Herceptin (trastuzumab) is indicated for adjuvant treatment of HER2 overexpressing node positive or node negative (ER/PR negative or with one high risk feature [see Clinical Studies] breast cancer….•with docetaxel and carboplatin.

Both drugs are FDA approved for breast cancer, carboplatin in combination with docetaxel and trastuzumab, which is not being used in this case, but not without it.

The combination is in a current trial: Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer, NCT00321633 This randomized phase II trial is studying carboplatin to see how well it works compared to docetaxel in treating women with metastatic genetic breast cancer. There is also a Chinese adjuvant study: Docetaxel Plus Carboplatin Versus Epirubicin Plus Cyclophosphamide Followed by Docetaxel as Adjuvant Treatment in Triple-negative Breast Cancer, NCT01150513.

Burris H 3rd, Yardley D, Jones S, et al. Phase II trial of trastuzumab followed by weekly paclitaxel/carboplatin as first-line treatment of patients with metastatic breast cancer. J Clin Oncol 2004;22:1621–1629.

Perez, Edith A. Carboplatin in Combination Therapy for Metastatic Breast Cancer
Oncologist 2004 9: 518-527

J. W. Chia, P. Ang, H. See, Z. Wong, L. Soh, Y. Yap, N. Wong Triple-negative metastatic/recurrent breast cancer: Treatment with paclitaxel/carboplatin combination chemotherapy. Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 1086

 

For adjuvant therapy:

Adjuvant chemotherapy is usually given after a mastectomy, and the TC regimen is recommended by NCCN and well studied. It is not stated, whether margins were negative of not. IT is nto clear if radiaton was also givne in December but it seems that not. Only one dose was given, on 12/4, and actual doses are not lsited, so I cannot dermine wheter this a weekly or tree weekly regimen.

Whereas TCH is well established for HER+ disease for adjuvant therpay, TC (Taxol and carboplatin) is not well established for HER negative disease.A recent review (Stover et al ) says: “It remains unclear how to incorporate platinum, and it is not known whether platinum could be used to substitute for anthracycline, taxane, or an alkylator rather than added to the current regimens.”.

 

NCCN, Breast Cancer BINV-K 2016

Neoadjuvant and Adjuvant Chemotherapy Considerations for Triple-Negative Breast Cancer

Daniel G. Stover, MD; Caitlin F. Bell; Sara M. Tolaney, MD, MPH – See more at: http://www.gotoper.com/publications/ajho/2016/2016mar/neoadjuvant-and-adjuvant-chemotherapy-considerations-for-triple-negative-breast-cancer#sthash.x64b5SQn.dpuf, 2016

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