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Introduction:

Paclitaxel and docetaxel were the
approved drugs for the  metastatic breast
cancer (MBC). Paclitaxel is derived from Bark of the Pacific yew tree (Taxus
brevifolia), and Docetaxel is synthesized from European yew tree (Taxus
baccata). Both Paclitaxel and Docetaxel demonstrate greater affinity for the
tubulin-binding site, a different microtubule polymerization pattern, longer
intracellular retention time and higher intracellular concentration in target
cells, greater thymidine phosphorylase upregulation, more potent antitumor
activity in in vitro and in vivo models.  The above mentioned chemical nature of these
drugs have proven efficacy in metastatic breast Cancer.

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Objective of the study:

Objective of the study is to assess the
safety and efficacy of the Docetaxel compared to Paclitaxel in patients with
advanced Breast Cancer that had progressed after an anthracycline-containing
chemotherapy regimen. During the study the antitumor activity and
toxicity of docetaxel 100 mg/m2 1-hour intravenous (IV) infusion every 21 days was
compared with paclitaxel 175 mg/m2 3-hour IV infusion every 21 days.The primary end points for the study
were toxicity and objective response.

Study Design:

This is a randomized,
controlled, open-label, multicenter, phase III study in order to compare the toxicity
and antitumor activity of docetaxel 100 mg/ sqm 1 hour intravenous infusion for
every 21 days compared to paclitaxel 175 mg/sqm 3-hour IV infusion every 21
days.

Patient Population:

Women aged 18
years or older suffering from adenocarcinoma of breast and disease progression
after one prior chemotherapy regimen for locally advanced or MBC, or with
locally advanced or MBC that progressed during or within 12 months of
completing an adjuvant or neoadjuvant chemotherapy regimen, were eligible for
the study. Prior therapy with an anthracycline was required, unless medically
contraindicated.

Results:

Study was conducted
for 7 years  (from 1994 to 2001) in 449
patients across 53 institutions. Statistical significant differences between
the Paclitaxel and Docetaxel
were not significant. Median age for subjects selected was found to be 56 years
for docetaxel patients whereas 54 years for paclitaxel patients. Both Paclitaxel and Docetaxel groups had
a median of two sites of disease, most patients were postmenopausal and more
than 90% of patients had metastatic disease. Many patients had estrogen
receptor positive tumors in docetaxel arm (51% in Docetaxel whereas 42% in
Paclitaxel). However, this difference was not Statistically not significant.

Intent-to-treat
population, both the median overall survival (OS, 15.4 v 12.7 months; hazard
ratio, 1.41; 95 percent Confidence Interval,1.15 to 1.73; Power= 0.03) and the
median time to progression (TTP, 5.7 months v 3.6 months; HR, 1.64; 95 Percent
CI, 1.33 to 2.02; P .0001) for docetaxel were significantly longer than for
paclitaxel, and the overall response rate (ORR, 32% v 25%; Power=0 .10) was
higher for docetaxel. Incidence of treatment-related nonhematologic toxicities and
hematologic was greater for docetaxel than for paclitaxel; however,
quality-of-life scores were not statistically different between treatment
groups over time.

Efficacy:

Statistical
Analysis in Intent to Treat population shows that the overall response rate was
higher for docetaxel than for paclitaxel (32% v 25 respectively; P=0.10; Table
3). Median response durations during the study were noted as 7.5 and 4.6 months
in the docetaxel and paclitaxel groups (P=0.01). Thirty percentage of
paclitaxel patients and 18% of docetaxel patients had progressive disease as
the best response.

Safety:

Four
treatment-related deaths occurred during the study in the docetaxel group among
them three were due to infection and one was as a result of Gastro Intestinal
Bleeding in nonthrombocytopenic patient. No deaths were reported in paclitaxel
group. Other toxicities seen were Neutropenia, Febrile neutropenia Thrombocytopenia
in both the groups. There was no significant statistical difference in terms of
Quality of Life among the two groups.

Conclusion:

Survival
advantage for docetaxel was observed when compared to paclitaxel group though
the incidence of toxicities were more leading to reduction in dosage and withdrawal
of treatment. Paclitaxel required slightly greater use of rescue of salvage
treatment. Hence, Docetaxel was found to be superior when compared to paclitaxel
in terms of Overall Survival and median time to progression. Overall Survival
Rate was higher for docetaxel. Nonhematologic and Hematologic toxicities
occurred more frequently in the patients of docetaxel group. Quality of life
scores were similar for both groups.

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