docetaxel and doxorubicin - breast cancer

J · medicine forum addict Joined: 07 May 2005 Posts: 93

http://www.forbes.com/lifestyle/health/feeds/hscout/2005/06/01/hscout526060.html

Chemotherapy Combo Increases Breast Cancer Survival
By Serena Gordon
HealthDay Reporter

WEDNESDAY, June 1 (HealthDay News) -- A combination of chemotherapy drugs
can increase the five-year survival rate of women with metastatic,
node-positive breast cancer by about 7 percent, a new Spanish study finds.

However, that gain doesn't come without a significant risk of serious side
effects, researchers report in the June 2 issue of the New England Journal
of Medicine.

The drugs are docetaxel and doxorubicin, and this combination plus a third
drug, cyclophosphamide, is currently one of the standard treatments used
for women with node-positive breast cancer. Node-positive breast cancer is
a malignancy that has spread beyond the breast to at least one lymph node.

"We have a reasonable new therapeutic option that can improve the
likelihood of cure of node-positive breast cancer patients. And the
benefits [extend] to all subsets of patients," including both pre-and
post-menopausal women and those with hormonal or genetic risk factors for
more aggressive disease, said study author Dr. Miguel Martin, chairman of
the Spanish Breast Cancer Research Group at the University Hospital in
Madrid.

Not everyone agrees that the combination of docetaxel and doxorubicin is a
good treatment option, however. In the May 18 issue of the Journal of the
American Medical Association, French researchers stopped a trial of this
drug combination because three women died from complications related to
the chemotherapy.

"A high risk of life-threatening complications associated with the
doxorubicin-docetaxel regimen was found in this open-label, controlled
trial," the researchers wrote, and they added the combination shouldn't be
used outside of carefully controlled clinical trials.

Martin disagreed with their conclusion, and said he was surprised they
stopped their study so abruptly. Like any chemotherapy drug, these
medications don't just interfere with cancer cell growth; they can also
affect normal cell growth, which can cause toxic side effects. Often,
chemotherapy medications can suppress the growth of white blood cells,
leaving patients vulnerable to infection.

But, according to Martin, doctors also have medications called growth
factors that can help counteract these effects. The French researchers
should have considered adding such medications to their trial, rather than
halting it altogether, Martin contends.

The Spanish study involved 1,480 women with node-positive breast cancer,
ranging between 18 and 70 years of age. All had surgery to remove cancer
from their breast, and were randomly assigned to a treatment group within
60 days of surgery. Each treatment group received six cycles of
chemotherapy.

Women in the TAC group (744) received 75 milligrams of docetaxel per
square meter of body surface area, 50 milligrams of doxorubicin per square
meter and 500 milligrams of cyclophosphamide per square meter, while women
in the FAC group (736) received 500 milligrams of fluouracil per square
meter, and the same dose of doxorubicin and cyclophosphamide.

The average follow-up time was 55 months. Two women from each group died
within 30 days of receiving treatment, though only one death from each
group was believed to be related to the medications.

The disease-free, five-year survival rate for the TAC group was 75
percent, compared with 68 percent in the FAC group. Overall five-year
survival rates were estimated to be 87 percent for the TAC group and 81
percent for women in the FAC group. Treatment with TAC resulted in a 30
percent reduction in the risk of death, according to the study.

Infections were more likely in women in the TAC group, though there were
no deaths attributed to infection.

This study, said Martin, "clearly shows that six cycles of the TAC
combination is superior to six cycles of the FAC combination" after
surgery for breast cancer.

"This was a well-done study that shows we have a very active agent in
docetaxel," said Dr. Jay Brooks, chairman of hematology and oncology at
Ochsner Clinic Foundation Hospital in New Orleans.

"The benefits of docetaxel clearly outweigh the disadvantages," said
Brooks, who added that more liberal use of growth factor medications might
help prevent infection and anemia caused by chemotherapy medications such
as docetaxel.

The bottom line though, said Brooks, is that "if someone in my family had
node-positive breast cancer, this drug would be used in their treatment."

J · medicine forum addict Joined: 07 May 2005 Posts: 93

http://www.jco.org/cgi/content/abstract/21/6/968

Journal of Clinical Oncology, Vol 21, Issue 6 (March), 2003: 968-975
© 2003 American Society for Clinical Oncology
Docetaxel and Doxorubicin Compared With Doxorubicin and Cyclophosphamide as
First-Line Chemotherapy for Metastatic Breast Cancer: Results of a Randomized,
Multicenter, Phase III Trial

Jean-Marc Nabholtz, Carla Falkson, Daniel Campos, Janos Szanto, Miguel Martin,
Stephen Chan, Tadeuz Pienkowski, Jerzy Zaluski, Tamas Pinter, Maciej Krzakowski,
Daniel Vorobiof, Robert Leonard, Ian Kennedy, Nacer Azli, Michael Murawsky,
Alessandro Riva, Pierre Pouillart for the TAX 306 Study Group

From the University of California at Los Angeles, CA; University of Pretoria,
Pretoria, and Sandton Oncology Centre, Johannesburg, South Africa; Hospital de San
Isidro, Buenos Aires, Argentina; Szt Margit Hospital, Budapest, and County Hospital,
Gyor, Hungary; Hospital Clinico San Carlos, Madrid, Spain; City Hospital Trust,
Nottingham, and Western General Hospital, Edinburgh, United Kingdom; Oncology
Center, Warsaw, and Oncology Center, Poznan, Poland; Waikato Hospital, Hamilton, New
Zealand; and Aventis Pharma, Antony, and Institut Curie, Paris, France.

Address reprint requests to Jean-Marc Nabholtz, MD, University of California, Los
Angeles, Peter Ueberroth Building Suite 3360B, Los Angeles, CA 90095-7077; email:
jmnabholtz@hotmail.com.

Purpose: This randomized, multicenter, phase III study compared doxorubicin and
docetaxel (AT) with doxorubicin and cyclophosphamide (AC) as first-line chemotherapy
(CT) in metastatic breast cancer (MBC).

Patients and Methods: Patients (n = 429) were randomly assigned to receive
doxorubicin 50 mg/m2 plus docetaxel 75 mg/m2 (n = 214) or doxorubicin 60 mg/m2 plus
cyclophosphamide 600 mg/m2 (n = 215) on day 1, every 3 weeks for up to eight cycles.

Results:

Time to progression (TTP; primary end point) and time to treatment failure (TTF)
were significantly longer with AT than AC (median TTP, 37.3 v 31.9 weeks; log-rank P
= .014; median TTF, 25.6 v 23.7 weeks; log-rank P = .048).

The overall response rate (ORR) was significantly greater for patients taking AT
(59%, with 10% complete response [CR], 49% partial response [PR]) than for those
taking AC (47%, with 7% CR, 39% PR) (P = .009).

The ORR was also higher with AT in patients with visceral involvement (58% v 41%;
liver, 62% v 42%; lung, 58% v 35%), three or more organs involved (59% v 40%), or
prior adjuvant CT (53% v 41%).

Overall survival (OS) was comparable in both arms.

Grade 3/4 neutropenia was frequent in both groups, although febrile neutropenia and
infections were more frequent for patients taking AT (respectively, 33% v 10%, P <
..001; 8% v 2%, P = .01). Severe nonhematologic toxicity was infrequent in both
groups, including grade 3/4 cardiac events (AT, 3%; AC, 4%).

Conclusion: AT significantly improves TTP and ORR compared with AC in patients with
MBC, but there is no difference in overall survival. AT represents a valid option
for the treatment of MBC.

Supported by Aventis Pharma, Antony, France.

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