Eighteen RCTs (9,032 women) were included.
Optimal dose of paclitaxel for metastatic breast cancer (5 RCTs, 2,208 patients).
The RCTs compared different doses and different regimens. The most favourable therapeutic index was obtained using 175 mg/m2 of paclitaxel, administered as an intravenous infusion over 3 hours every 3 weeks. Higher doses or longer infusion periods were associated with greater toxicity without a clear survival benefit.
3-hour versus 24-hour infusion of paclitaxel (2 RCTs).
One RCT involving 563 patients with stage IIIB or stage IV breast cancer compared 3- and 24-hour infusions of paclitaxel (250 mg/m2). After 4 cycles, the 24-hour infusion produced a significantly higher response rate (51 versus 41%), similar median progression-free survival (7.2 versus 6.3 months), and similar median overall survival (21.9 versus 21.1 months). Grade 4 toxicity was more common in the 24-hour infusion arm (23 versus 12%). The other RCT (521 patients) found no difference in response rates (29 versus 31%) between the 24- and 3-hour infusions (175 mg/m2). However, it did find a statistically-significant increase for the 24-hour infusion in median time to progression (4.6 versus 3.8 months; p=0.021) and for median survival (13.4 versus 9.8 months; p=0.021). The 24-hour infusion was associated with significantly more grade 4 neutropenia, mucositis, and any diarrhoea. The 3-hour infusion was associated with significantly more neuropathy.
3-hour versus 96-hour infusion of paclitaxel (1 RCT, 179 patients).
The single RCT found no significant difference between the treatment arms.
Doses of 175 versus 135 mg/m2 paclitaxel over 3 hours (1 RCT, 471 patients).
Increased toxicity (grade 3 to 4 leucopenia, neuropathy, febrile neutropenia, grade 3 myalgia or arthralgia) was found in the higher dose arm. However, there was no significant difference between the treatment arms in terms of the overall response rate (29 versus 22%) or median survival (11.7 versus 10.5 months). The quality of life-adjusted time to progression analysis favoured the higher dose (175 mg/m2) arm. Doses of 175 versus 210 versus 250 mg/m2 paclitaxel over 3 hours (1 RCT, 474 patients).
There was no significant difference between the treatment arms in terms of the response rates: the response rates were 22, 26 and 21% for doses of 175, 210 and 250 mg/m2, respectively. The 175 mg/m2 arm was associated with significantly less grade 4 granulocytopenia, grade 3 sensory neuropathy, grade 3 motor neuropathy and grade 3 myalgias, than the other regimens.
Taxanes as first-line therapy for metastatic disease (7 RCTs, 2,479 patients).
The response rates across the treatment arms ranged from 15 to 68%, and the median time to progression ranged from 4.1 to 8.7 months.
The addition of trastuzumab to paclitaxel resulted in improved survival in women with metastatic breast cancer that overexpressed the HER2/neu protein. The single RCT (178 patients) reported a significant increase in response rate (38 versus 15%), median time to progression (6.7 versus 2.5 months), and median response duration (8.3 versus 4.3 months) in the combination therapy arm. The following adverse reactions were significantly more common in the combination arm: cardiac dysfunction, fever, chills, abdominal pain, infection, nausea, diarrhoea, cough, rhinitis, sinusitis and rash. Quality of life was not assessed.
Taxanes as second-line therapy (3 RCTs, 850 patients).
The response rates across the treatment arms ranged from 12.1 to 42.1%, and the median time to progression ranged from 2.6 to 6.0 months.
Two RCTs looked at the effect of using docetaxel (100 mg/m2) as second-line therapy for anthracycline-resistant disease. One RCT (392 patients) found statistical improvements in the response rate (30 versus 12%; p<0.05), median time to progression (4.4 versus 2.6 months; p<0.05) and median survival (11.4 versus 8.7 months; p<0.05), when docetaxel was compared with mitomycin plus vinblastine. There was no difference in the global health scores between the treatment arms. Docetaxel was associated with more grade 3 to 4 neutropenia, infection, stomatitis, skin rash, nail disorders, diarrhoea, asthenia, and neurosensory toxicity.
The other RCT (283 patients, 199 included in the analysis) found statistical improvements in the response rate (42 versus 19%; p<0.05) and median time to progression (6.0 versus 3.0 months; p<0.05), when docetaxel was compared with methotrexate plus 5-fluorouracil. Docetaxel was associated with greater rates of leucopenia, infection, asthenia, fluid retention, nail toxicity, and neuropathy.
Another RCT (175 patients) found no significant difference between docetaxel and a combination of vinorelbine and 5-fluorouracil
Early-stage breast cancer.
One RCT (3,121 patients) found that, compared with 4 cycles of doxorubicin, 4 cycles of doxorubicin followed by 4 cycles of paclitaxel increased the disease-free survival at 2 years (90 versus 86%; p<0.05) and improved the survival in women with axillary-node positive breast cancer.