Benefit risk assessment and update on the use of docetaxel in the management of breast cancer

Figures & data

Figure 1 Chemical structure of docetaxel.

Table 1 Randomized trials of docetaxel in combination

Author	O’Shaughnessy et al^Citation25	Pacilio et al^Citation26	Sparano et al^Citation27
Study design	Randomized	Randomized	Randomized
Primary endpoint	TTP	ORR	TTP
Secondary endpoint	OS, ORR	OS, TTP	OS, ORR
Investigational arm	Capecitabine 1,250 mg/m^2 twice daily on days 1 to 14 and docetaxel 75 mg/m^2 on day 1	Epirubicin 75 mg/m^2 and docetaxel 80 mg/m^2	Pegylated liposomal doxorubicin 30 mg/m^2 and docetaxel 60 mg/m^2
Control arm Patient population	Docetaxel 100 mg/m^2 on day 1* Anthracycline-pretreated metastatic breast cancer	Docetaxel 100 mg/m^2 on day 1* Anthracycline-pretreated in the neoadjuvant/adjuvant setting. No previous chemotherapy for metastatic breast cancer	Docetaxel 75 mg/m^2 on day 1* Anthracycline-pretreated in the neoadjuvant/adjuvant setting; prior hormonal treatment and/or one regimen of chemotherapy for metastatic disease were acceptable

Note:

* All regimens are 3-week cycles.

Abbreviations: TTP, time to progression; ORR, objective response rate; OS, overall survival.

Table 2 Common toxicities in Phase II trials of docetaxel in the metastatic setting

	Fumoleau et al^Citation43	Valero et al^Citation22
Dose administered	100 mg/m^2	100 mg/m^2
Neutropenia (grade 3–4)	97%	96%
Fluid retention	89%	43%*
Neurosensory disorders	81.1%	6%

Note:

* Protocol modification at midpoint analysis commenced prophylactic corticosteroid therapy for edema.

Table 3 Common toxicities associated with docetaxel

Trial	Chan et al^Citation23	BCIRG-001^Citation29	BIG 02-98^Citation30	E2917^Citation31	BCIRG-006^Citation44
Dose administered	100 mg/m^2	75 mg/m^2	50–100 mg/m^2	60 mg/m^2	75–100 mg/m^2
Setting	Metastatic	Adjuvant	Adjuvant	Adjuvant	Adjuvant
Neutropenia (grade 3–4)	93.5%	65.6% (P < 0.001)	28%	54% (P < 0.05)	65.9%
Fluid retention	59.7%	33.7% (P < 0.001)	0.3%
Neurosensory disorders	42.8% (P ≤ 0.05)	25.5% (P < 0.001)	0.8%	1%	36%
Diarrhea	50.3% (P ≤ 0.05)	35.2%	6%	5%	5.4%
Nail disorder	44% (P ≤ 0.05)	18.5%	NA		28.7%

Table 4 Toxicity profiles of taxanes in a head to head comparison

	Paclitaxel 3-week cycle	Paclitaxel weekly	Docetaxel 3-week cycle	Docetaxel weekly
Total % of grade 3–4 toxicities	30%	28%	71%‡	45%‡
Neutropenia (grade 4)	4%	2%	46%	3%
Febrile neutropenia (grade 3, 4)	<0.5%	1%	16%	1%
Edema (grades 2–4)	3.5%	8%	12.5%	10.5%
Nail changes (grades 2–4)	2%	7%	11.5%	25%
Diarrhea (grades 2–4)	3%	6%	10%	10%
Sensory neuropathy (grades 2–4)	17%	21.5%	13%	10.5%

Notes: All patients were pretreated with doxorubicin/cyclophosphamide.

‡ P < 0.001.³⁹

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