[MOL] Breast Cancer Info

["Lillian" <firefly@islc.net>]

 

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American Society of Clinical Oncology 35th Annual Meeting
Day 2 - May 16, 1999

Weekly Taxanes and Liposomal Anthracyclines for Advanced Breast Cancer: Widening Studies in Clinical Practice; And MMP Inhibitors

Harold J. Burstein, MD, PhD -- Contributing Author: Joseph Sparano, MD

Weekly taxanes are being widely used to treat metastatic breast cancer. In addition, new formulations of anthracyclines are coming into clinical trials, with the promise of equal activity but fewer side effects. Several posters presented Sunday testified to the rapidly evolving interest in these regimens. The growing experience with these different regimens is likely to have significant clinical impact in the near future.

Activity of Weekly Taxanes in Metastatic Breast Cancer

Historically, taxanes such as paclitaxel (Bristol Myers) and docetaxel (Rhône-Poulenc Rorer) have been administered primarily on an every-3-week treatment schedule. It was on the strength of activity data for this every-3-week schedule that these drugs were FDA-approved for treatment. Previous studies have explored whether more frequent, lower-dose infusion of taxanes might alter the activity or side-effect profiles of these treatments. Phase I studies from investigators at several institutes have demonstrated that weekly administration of paclitaxel and docetaxel are reasonably well tolerated.

Weekly paclitaxel therapy for metastatic breast cancer has been reported in a single Phase II study from researchers at Memorial Sloan-Kettering Cancer Center. Dr. Andy Seidman^[1] has reported that weekly administration of paclitaxel at doses from 60-100 mg/m²/week is associated with a response rate of approximately 52%. A number of other studies of weekly taxane treatment were presented at the 35th ASCO meeting and are summarized in Table I.

Table I. Studies of Weekly Taxane Treatment

	Abstract or Ref	Line of Therapy for Metastatic Disease	Schedule	Weekly Taxane Dose (mg/m2)	Response Rate
Paclitaxel
Seidman[1]	Ref 1	1-3	Weekly	80-100	52%
Perez[11]	Abst 480	1-4	Weekly	80	23
		1			33
Fornier[12]	Abst 482	1-4	Weekly	90 with Herceptin	44 (HER2-negative subset)
Loesch[13]	Abst 445	1	Weekly x 3, 1 week off	80 with 5-FU and leucovorin	49
Docetaxel
Burstein[14]	Abst 484	1-2	Weekly x 6, 2 weeks off	40	41
Climent[15]	Abst 453	> 1	Weekly	35	35% to 50%

These Phase II studies demonstrate that weekly administration of taxanes is associated with reasonable clinical activity in treating metastatic breast cancer. It is apparent that weekly administration alters the toxicity profile of taxane therapy. With weekly administration of either paclitaxel or docetaxel, myelosuppression is dramatically less than that seen with other treatment schedules. Grade 4 neutropenia is exceedingly rare, and myelosuppression is not cumulative. Other hematologic toxicity is also very mild.

Patients appear to tolerate weekly infusions of taxanes reasonably well. With protracted therapy, other side effects become more apparent. Paclitaxel has been associated with neuropathy. Docetaxel has been associated with fluid retention, fatigue, and eye tearing/conjunctivitis.

It is not known how effective weekly taxane administration is in comparison to administration on an every-3-week schedule. Randomized studies will be needed to answer this question. Similarly, it is not known how paclitaxel and docetaxel compare with each other with regard to activity on a weekly schedule.

Weekly Paclitaxel After Prior Paclitaxel Therapy

An interesting observation has been the reported success of taxane therapy on re-treatment with a different administration schedule following prior taxane therapy. Dr. A. Alvarez^[2] presented a Phase II study looking at treatment with weekly paclitaxel in patients with metastatic breast cancer who had previously received paclitaxel on an every-3-week basis. Despite havin