A Study of Docetaxel Monotherapy or DOXIL and Docetaxel in Patients With Advanced Breast Cancer

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00091442
• Collaborator: (none)
• Enrollment: 751
• Locations: 151
• Arms: 2
• Duration (Months): 51
• Patients Per Site: 5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate whether the time to progression for the DOXIL and docetaxel combination therapy group was superior to that of the group treated with docetaxel monotherapy in participants with advanced breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Docetaxel; Drug: DOXIL	Phase 3

Detailed Description

This is a randomized (the study medication is assigned by a random order), active control (study medication will be compared with available standard care of treatment), parallel-group (each treatment group will be treated simultaneously at the same time and each participant only receives one treatment regimen as assigned), open-label (both the investigator and the participant know the intervention received by the participant), multicenter study designed to determine if women with locally advanced or metastatic breast cancer, who were previously treated with prior anthracycline therapy in the neoadjuvant (administration of treatment before surgery) or adjuvant setting (administration of treatment after surgery), and who also had a disease-free interval of at least 12 months since the end of their last cytotoxic therapy, would benefit from the addition of DOXIL to docetaxel therapy. Approximately 751 participants will be randomly assigned to either receive docetaxel monotherapy or DOXIL in combination with docetaxel therapy. Treatment is to continue until disease progression or the occurrence of unacceptable treatment related toxicity. Safety evaluations will include assessments of adverse events which will be recorded from the first study related procedure until 30 days after the last dose of medication; clinical laboratory tests and tests for cardiac function (multiple gated acquisition scan/echocardiogram and electrocardiogram) which will be monitored throughout the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 751 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Controlled Study of Docetaxel Monotherapy or Docetaxel and DOXIL for the Treatment of Advanced Breast Cancer
• Study Start Date: Sep 1, 2004
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DOXIL and docetaxel combination therapy DOXIL and docetaxel combination therapy: DOXIL 30 mg/m2 solution administered by intravenous infusion, followed by docetaxel 60 mg/m2 administration by intravenous infusion over 1 hour on Day 1 of every 21-day cycle.	Drug: Docetaxel; Docetaxel monotherapy: docetaxel 75 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle. DOXIL in combination with docetaxel: docetaxel 60 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle; Drug: DOXIL; DOXIL 30 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle.; Other Names: DOXIL in combination with Docataxel
Active Comparator: Docetaxel monotherapy Docetaxel monotherapy: Docetaxel 75 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle	Drug: Docetaxel; Docetaxel monotherapy: docetaxel 75 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle. DOXIL in combination with docetaxel: docetaxel 60 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle

Outcome Measures

Primary Outcome Measures

1. Time to Progression [From date of randomization until date of disease progression or death, whichever occurred first, until approximately 485 events of disease progression or death were observed, as assessed approximately 15 months after the last patient was enrolled]

   Time interval in months between the date of randomization and the date of disease progression or death due to progression, whichever occurred first.

Secondary Outcome Measures

1. Overall Survival [From the date of randomization until the participant's death from any cause, as assessed until approximately 485 death events were observed which is assessed approximately 25 months after the last patient was enrolled]

   Time interval in months between the date of randomization and the participant's death from any cause.

2. Response Rate: Number of Participants in the Evaluable Population Who Achieved a Complete Response (CR) or Partial Response (PR) [Up to 30 to 42 days after last dose of study medication]

   Number of participants in the evaluable population who achieved a CR or PR as per Response Evaluation Criteria In Solid Tumors (RECIST) criteria. CR: Disappearance of all target lesions and PR: at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD. Response was assessed by Computed Tomography (CT)/Magnetic Resonance Imaging (MRI).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Females with locally advanced or metastatic breast cancer who received prior anthracycline therapy in the neoadjuvant or adjuvant setting, and had at least a 12-month disease-free interval since the end of their last cytotoxic therapy, were eligible for the study

• Participants who received prior hormonal therapy, or no more than 1 cytotoxic chemotherapy regimen (anthracyclines, taxanes, or antitubulin agents were not permitted), or both for advanced disease

• Participants with normal cardiac function, as evidenced by a normal left ventricular ejection fraction

Exclusion Criteria:

• More than 1 prior cytotoxic chemotherapy regimen for advanced breast cancer

• Treatment of advanced breast cancer with an anthracycline, paclitaxel, docetaxel, vinorelbine, or vinblastine (prior treatment of advanced breast cancer with 1 regimen that included alkylating agents or antimetabolite agents was acceptable)

• Less than 2 months since the last dose of trastuzumab

• Less than 3 weeks since last dose of tamoxifen or fulvestrant, or less than 1 week since the last dose of other hormonal therapy

• Radiation to areas of disease within 30 days before study enrollment

• History of New York Heart Association Class II or greater cardiac disease or other clinical evidence of congestive heart failure

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Hoover	Alabama	United States
2		Fountain Valley	California	United States
3		Long Beach	California	United States
4		Los Angeles	California	United States
5		Palm Springs	California	United States
6		Newark	Delaware	United States
7		Lakeland	Florida	United States
8		Fort Gordon	Georgia	United States
9		Centralia	Illinois	United States
10		Joliet	Illinois	United States
11		Indianapolis	Indiana	United States
12		Lexington	Kentucky	United States
13		Louisville	Kentucky	United States
14		Lafayette	Louisiana	United States
15		Baltimore	Maryland	United States
16		Jackson	Mississippi	United States
17		Las Vegas	Nevada	United States
18		Newark	New Jersey	United States
19		Albuquerque	New Mexico	United States
20		Bronx	New York	United States
21		Cooperstown	New York	United States
22		New York	New York	United States
23		Gastonia	North Carolina	United States
24		Philadelphia	Pennsylvania	United States
25		Upland	Pennsylvania	United States
26		Providence	Rhode Island	United States
27		Charleston	South Carolina	United States
28		N Charleston	South Carolina	United States
29		Fort Worth	Texas	United States
30		Pasadena	Texas	United States
31		Plovdiv		Bulgaria
32		Shumen		Bulgaria
33		Sofia		Bulgaria
34		Stara Zagora		Bulgaria
35		Varna		Bulgaria
36		Tartu N/A		Estonia
37		Rabat		France
38		Tunis		France
39		Budapest N/A		Hungary
40		Budapest		Hungary
41		Debrecen		Hungary
42		Szeged		Hungary
43		Szekesfehervar		Hungary
44		Zalaegerszeg		Hungary
45		Ashkelon		Israel
46		Haifa		Israel
47		Jerusalem		Israel
48		Ramat-Gan		Israel
49		Tel Aviv		Israel
50		Riga		Latvia
51		Kaunas		Lithuania
52		Vilnius		Lithuania
53		Arnhem		Netherlands
54		Capelle Aan Den Ijssel		Netherlands
55		Den Haag		Netherlands
56		Roosendaal		Netherlands
57		Bialystok		Poland
58		Bydgoszcz		Poland
59		Bytom		Poland
60		Gdansk		Poland
61		Gdynia N/A		Poland
62		Gliwice		Poland
63		Kielce		Poland
64		Koszalin		Poland
65		Krakow		Poland
66		Lodz		Poland
67		Lublin		Poland
68		Olsztyn		Poland
69		Poznan		Poland
70		Warsaw		Poland
71		Coimbra		Portugal
72		Matosinhos N/A		Portugal
73		Bacau		Romania
74		Bucuresti		Romania
75		Cluj-Napoca		Romania
76		Hunedoara		Romania
77		Iasi		Romania
78		Onesti		Romania
79		Timisoara		Romania
80		Arkhangelsk		Russian Federation
81		Balashikha		Russian Federation
82		Barnaul		Russian Federation
83		Chelyabinsk		Russian Federation
84		Ekaterinburg		Russian Federation
85		Engels Saratov Region		Russian Federation
86		Irkutsk		Russian Federation
87		Ivanovo		Russian Federation
88		Izhevsk		Russian Federation
89		Kazan		Russian Federation
90		Krasnodar		Russian Federation
91		Leningrad Region		Russian Federation
92		Lipetsk		Russian Federation
93		Moscow N/A		Russian Federation
94		Moscow Region		Russian Federation
95		Moscow		Russian Federation
96		Murmansk		Russian Federation
97		N Novgorod N/A		Russian Federation
98		Nizhny Novgorod		Russian Federation
99		Novosibirsk		Russian Federation
100		Obninsk		Russian Federation
101		Omsk		Russian Federation
102		Orel		Russian Federation
103		Petrozavodsk		Russian Federation
104		Pyatigorsk		Russian Federation
105		Rostov-Na-Donu		Russian Federation
106		Ryazan		Russian Federation
107		Samara N/A		Russian Federation
108		Smolensk		Russian Federation
109		St Petersburg N/A		Russian Federation
110		St. Petersburg		Russian Federation
111		Stavropol		Russian Federation
112		Tomsk		Russian Federation
113		Tver		Russian Federation
114		Ulianovsk		Russian Federation
115		Vladimir		Russian Federation
116		Volgograd		Russian Federation
117		Voronezh		Russian Federation
118		Yaroslavl		Russian Federation
119		Beograd		Serbia
120		Nis		Serbia
121		Sremska Kamenica		Serbia
122		Cape Town		South Africa
123		Johannesburg		South Africa
124		Kimberley		South Africa
125		Parktown		South Africa
126		Port Elizabeth		South Africa
127		Pretoria Gauteng		South Africa
128		Pretoria		South Africa
129		Bilbao Vizcaya		Spain
130		Lérida		Spain
131		Madrid		Spain
132		Santander N/A		Spain
133		Sevilla		Spain
134		Cherkassy		Ukraine
135		Chernivtsi		Ukraine
136		Dnepropetrovsk		Ukraine
137		Donetsk		Ukraine
138		Kharkov		Ukraine
139		Kiev		Ukraine
140		Lugansk		Ukraine
141		Lutsk		Ukraine
142		Odessa		Ukraine
143		Poltava		Ukraine
144		Simferopol		Ukraine
145		Uzhgorod		Ukraine
146		Vinnitsa		Ukraine
147		Zhitomir		Ukraine
148		Huddersfield		United Kingdom
149		Manchester		United Kingdom
150		Nottingham		United Kingdom
151		Sutton		United Kingdom

Sponsors and Collaborators

• Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Investigators

• Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• ClinicalTrials.gov Identifier: NCT00091442
• Other Study ID Numbers: CR004120; DOXILBCA3001; NCT00343538
• First Posted: Sep 13, 2004
• Last Update Posted: Apr 21, 2014
• Last Verified: Apr 1, 2014

• Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.: Breast Cancer; Advanced breast cancer; Breast Tumors; Cancer of Breast; Human Mammary Carcinoma; Mammary Neoplasms, Human; DOXIL; Docetaxel
• Additional relevant MeSH terms: Breast Neoplasms; Docetaxel; Liposomal doxorubicin

Study Results

Participant Flow

Recruitment Details	A total of 751 participants were enrolled and randomized at 143 sites in 19 countries.
Pre-assignment Detail	751 participants were randomly assigned to 2 treatment groups (Docetaxel: 373 ; DOXIL+docetaxel: 378). 750 participants received treatment (Docetaxel: 373; DOXIL+docetaxel: 377). 1 participant in DOXIL+docetaxel treatment group did not receive treatment.

Arm/Group Title	Docetaxel	DOXIL+Docetaxel
Arm/Group Description	Docetaxel monotherapy: Docetaxel 75 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle.	DOXIL and docetaxel combination: DOXIL 30 mg/m2 solution administered by intravenous infusion, followed by docetaxel 60 mg/m2 administration by intravenous infusion over 1 hour on Day 1 of every 21-day cycle.
Period Title: Overall Study
STARTED	373	378
COMPLETED	4	5
NOT COMPLETED	369	373

Baseline Characteristics

Arm/Group Title	Docetaxel	DOXIL+Docetaxel	Total
Arm/Group Description	Docetaxel monotherapy: Docetaxel 75 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle.	DOXIL and docetaxel combination: DOXIL 30 mg/m2 solution administered by intravenous infusion, followed by docetaxel 60 mg/m2 administration by intravenous infusion over 1 hour on Day 1 of every 21-day cycle.	Total of all reporting groups
Overall Participants	373	378	751
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.0 (9.23)	52.8 (9.17)	52.4 (9.20)
Sex: Female, Male (Count of Participants)
Female	373 100%	378 100%	751 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Secondary Outcome

Title	Overall Survival
Description	Time interval in months between the date of randomization and the participant's death from any cause.
Time Frame	From the date of randomization until the participant's death from any cause, as assessed until approximately 485 death events were observed which is assessed approximately 25 months after the last patient was enrolled

Outcome Measure Data

Analysis Population Description

Intent to Treat: If the date of death was unknown, the data were censored at the date that the participant was last known to have been alive.

Arm/Group Title	Docetaxel	DOXIL+Docetaxel
Arm/Group Description	Docetaxel monotherapy: Docetaxel 75 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle.	DOXIL and docetaxel combination: DOXIL 30 mg/m2 solution administered by intravenous infusion, followed by docetaxel 60 mg/m2 administration by intravenous infusion over 1 hour on Day 1 of every 21-day cycle.
Measure Participants	373	378
Median (95% Confidence Interval) [Months]	20.7	20.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Docetaxel, DOXIL+Docetaxel
	Comments	Null Hypothesis: Designed to detect an improvement in median survival from 15 months to 19.5 months with 80% power.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5988
	Comments	Not adjusted for multiple comparison.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.06
	Confidence Interval	() 95%; 0.86 to 1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Response Rate: Number of Participants in the Evaluable Population Who Achieved a Complete Response (CR) or Partial Response (PR)
Description	Number of participants in the evaluable population who achieved a CR or PR as per Response Evaluation Criteria In Solid Tumors (RECIST) criteria. CR: Disappearance of all target lesions and PR: at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD. Response was assessed by Computed Tomography (CT)/Magnetic Resonance Imaging (MRI).
Time Frame	Up to 30 to 42 days after last dose of study medication

Outcome Measure Data

Analysis Population Description

Evaluable population: Included all randomized participants who received at least 1 dose of study medication (DOXIL or docetaxel), and who had at least 1 postbaseline tumor assessment.

Arm/Group Title	Docetaxel	DOXIL+Docetaxel
Arm/Group Description	Docetaxel monotherapy: Docetaxel 75 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle.	DOXIL and docetaxel combination: DOXIL 30 mg/m2 solution administered by intravenous infusion, followed by docetaxel 60 mg/m2 administration by intravenous infusion over 1 hour on Day 1 of every 21-day cycle.
Measure Participants	364	370
Number [Participants]	95 25.5%	129 34.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Docetaxel, DOXIL+Docetaxel
	Comments	Null hypothesis - no difference in response rate between the two treatment groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0085
	Comments	Not adjusted for multiple comparison
	Method	Cochran-Mantel-Haenszel
	Comments

3. Primary Outcome

Title	Time to Progression
Description	Time interval in months between the date of randomization and the date of disease progression or death due to progression, whichever occurred first.
Time Frame	From date of randomization until date of disease progression or death, whichever occurred first, until approximately 485 events of disease progression or death were observed, as assessed approximately 15 months after the last patient was enrolled

Outcome Measure Data

Analysis Population Description

Intent to Treat: For patients who were progression free at the time of data cutoff, data were censored for time to progression at the time of their last tumor assessment.

Arm/Group Title	Docetaxel	DOXIL+Docetaxel
Arm/Group Description	Docetaxel monotherapy: Docetaxel 75 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle.	DOXIL and docetaxel combination: DOXIL 30 mg/m2 solution administered by intravenous infusion, followed by docetaxel 60 mg/m2 administration by intravenous infusion over 1 hour on Day 1 of every 21-day cycle.
Measure Participants	373	378
Median (95% Confidence Interval) [Months]	7.0	9.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Docetaxel, DOXIL+Docetaxel
	Comments	Null hypothersis - no difference in Time to Progression (TTP) between the two treatment groups. Designed to detect an improvement in median TTP from 6 months to 7.8 months with 80% power, assuming exponential survival distribution.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.65
	Confidence Interval	() 95%; 0.55 to 0.77
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	From first dose of study medication until 30 days after the last dose of study medication.
Adverse Event Reporting Description	751 participants were randomly assigned to 2 treatment groups (Docetaxel: 373 ; DOXIL+docetaxel: 378). 750 participants received treatment (Docetaxel: 373; DOXIL+docetaxel: 377). 1 participant in DOXIL+docetaxel treatment group did not receive treatment.
Arm/Group Title	Docetaxel		DOXIL+Docetaxel
Arm/Group Description	Docetaxel monotherapy: Docetaxel 75 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle.		DOXIL and docetaxel combination: DOXIL 30 mg/m2 solution administered by intravenous infusion, followed by docetaxel 60 mg/m2 administration by intravenous infusion over 1 hour on Day 1 of every 21-day cycle.
All Cause Mortality
	Docetaxel		DOXIL+Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Docetaxel		DOXIL+Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	59/373 (15.8%)		69/377 (18.3%)
Blood and lymphatic system disorders
Neutropenia	14/373 (3.8%)		17/377 (4.5%)
Febrile neutropenia	10/373 (2.7%)		10/377 (2.7%)
Leukopenia	1/373 (0.3%)		4/377 (1.1%)
Anaemia	2/373 (0.5%)		2/377 (0.5%)
Lymphadenopathy	0/373 (0%)		1/377 (0.3%)
Cardiac disorders
cardiac failure	2/373 (0.5%)		1/377 (0.3%)
Atrial fibrillation	1/373 (0.3%)		1/377 (0.3%)
Pericardial effusion	2/373 (0.5%)		0/377 (0%)
Cardiac failure congestive	1/373 (0.3%)		0/377 (0%)
Cardiomyopathy	0/373 (0%)		1/377 (0.3%)
Supraventricular tachycardia	0/373 (0%)		1/377 (0.3%)
Tachycardia	0/373 (0%)		1/377 (0.3%)
Diabetic ketoacidosis	1/373 (0.3%)		0/377 (0%)
Gastrointestinal disorders
Vomiting	3/373 (0.8%)		4/377 (1.1%)
Diarrhoea	2/373 (0.5%)		3/377 (0.8%)
Nausea	3/373 (0.8%)		2/377 (0.5%)
Stomatitis	1/373 (0.3%)		4/377 (1.1%)
Abdominal pain	2/373 (0.5%)		0/377 (0%)
Abdominal mass	1/373 (0.3%)		0/377 (0%)
Dysphagia	0/373 (0%)		1/377 (0.3%)
Gastric haemorrhage	0/373 (0%)		1/377 (0.3%)
Gastrointestinal ulcer	0/373 (0%)		1/377 (0.3%)
Ileus	1/373 (0.3%)		0/377 (0%)
Intestinal ischaemia	0/373 (0%)		1/377 (0.3%)
Peritonitis	0/373 (0%)		1/377 (0.3%)
General disorders
Pyrexia	3/373 (0.8%)		6/377 (1.6%)
Asthenia	1/373 (0.3%)		3/377 (0.8%)
Infusion related reaction	0/373 (0%)		2/377 (0.5%)
Death	1/373 (0.3%)		0/377 (0%)
Multi-organ failure	0/373 (0%)		1/377 (0.3%)
Hepatobiliary disorders
Biliary colic	1/373 (0.3%)		0/377 (0%)
Cholecystitis acute	1/373 (0.3%)		0/377 (0%)
Cholelithiasis	0/373 (0%)		1/377 (0.3%)
Hyperbilirubinaemia	1/373 (0.3%)		0/377 (0%)
Immune system disorders
Anaphylactic reaction	0/373 (0%)		1/377 (0.3%)
Infections and infestations
Pneumonia	0/373 (0%)		12/377 (3.2%)
Neutropenic sepsis	4/373 (1.1%)		0/377 (0%)
Cellulitis	1/373 (0.3%)		2/377 (0.5%)
Urinary tract infection	1/373 (0.3%)		1/377 (0.3%)
Appendicitis	0/373 (0%)		1/377 (0.3%)
Breast abscess	1/373 (0.3%)		0/377 (0%)
Catheter related infection	1/373 (0.3%)		0/377 (0%)
Catheter site cellulitis	1/373 (0.3%)		0/377 (0%)
Cystitis	0/373 (0%)		1/377 (0.3%)
Erysipelas	1/373 (0.3%)		0/377 (0%)
Folliculitis	0/373 (0%)		1/377 (0.3%)
Groin abscess	1/373 (0.3%)		0/377 (0%)
Infection	0/373 (0%)		1/377 (0.3%)
Lung infection	1/373 (0.3%)		0/377 (0%)
Pulpitis dental	1/373 (0.3%)		0/377 (0%)
Pyelonephritis	1/373 (0.3%)		0/377 (0%)
Skin infection	0/373 (0%)		1/377 (0.3%)
Staphylococcal infection	1/373 (0.3%)		0/377 (0%)
Subcutaneous abscess	0/373 (0%)		1/377 (0.3%)
Tooth abscess	0/373 (0%)		1/377 (0.3%)
Vaginal infection	0/373 (0%)		1/377 (0.3%)
Viral infection	0/373 (0%)		1/377 (0.3%)
Vulvitis	0/373 (0%)		1/377 (0.3%)
Injury, poisoning and procedural complications
Fall	1/373 (0.3%)		1/377 (0.3%)
Alcohol poisoning	0/373 (0%)		1/377 (0.3%)
Humerus fracture	1/373 (0.3%)		0/377 (0%)
Upper limb fracture	1/373 (0.3%)		0/377 (0%)
Investigations
Alanine aminotransferease increased	1/373 (0.3%)		0/377 (0%)
Aspartate aminotransferase increased	1/373 (0.3%)		0/377 (0%)
Blood creatinine increased	1/373 (0.3%)		0/377 (0%)
Blood urea increased	1/373 (0.3%)		0/377 (0%)
Ejection fraction decreased	0/373 (0%)		1/377 (0.3%)
Metabolism and nutrition disorders
Dehydration	3/373 (0.8%)		2/377 (0.5%)
Hypocalcaemia	0/373 (0%)		2/377 (0.5%)
Hypokalaemia	1/373 (0.3%)		1/377 (0.3%)
Hypercalcaemia	0/373 (0%)		1/377 (0.3%)
Hyperglycaemia	0/373 (0%)		1/377 (0.3%)
Hypomagnesaemia	1/373 (0.3%)		0/377 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/373 (0%)		1/377 (0.3%)
Bone pain	1/373 (0.3%)		0/377 (0%)
Pathological fracture	1/373 (0.3%)		0/377 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma	1/373 (0.3%)		0/377 (0%)
Metastasis	0/373 (0%)		1/377 (0.3%)
Neoplasm malignant	0/373 (0%)		1/377 (0.3%)
Nervous system disorders
Convulsion	1/373 (0.3%)		1/377 (0.3%)
Heachache	1/373 (0.3%)		1/377 (0.3%)
Loss of consciousness	0/373 (0%)		2/377 (0.5%)
Brain stem syndrome	0/373 (0%)		1/377 (0.3%)
Cerebrovascular accident	0/373 (0%)		1/377 (0.3%)
Dizziness	0/373 (0%)		1/377 (0.3%)
Grand mal convulsion	0/373 (0%)		1/377 (0.3%)
Hemiplegia	1/373 (0.3%)		0/377 (0%)
Speech disorder	0/373 (0%)		1/377 (0.3%)
Syncope	0/373 (0%)		1/377 (0.3%)
Psychiatric disorders
Anxiety	1/373 (0.3%)		0/377 (0%)
Mental status changes	0/373 (0%)		1/377 (0.3%)
Reproductive system and breast disorders
Metrorrhagia	1/373 (0.3%)		0/377 (0%)
Uterine polyp	1/373 (0.3%)		0/377 (0%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	4/373 (1.1%)		0/377 (0%)
Pulmonary embolism	2/373 (0.5%)		2/377 (0.5%)
Dyspnoea	2/373 (0.5%)		1/377 (0.3%)
Acute respiratory failure	1/373 (0.3%)		1/377 (0.3%)
Respiratory arrest	0/373 (0%)		2/377 (0.5%)
Respiratory failure	0/373 (0%)		2/377 (0.5%)
Asthma	0/373 (0%)		1/377 (0.3%)
Asthmatic crisis	1/373 (0.3%)		0/377 (0%)
Bronchial haemorrhage	0/373 (0%)		1/377 (0.3%)
Bronchospasm	0/373 (0%)		1/377 (0.3%)
Hydrothorax	1/373 (0.3%)		0/377 (0%)
Hypoxia	0/373 (0%)		1/377 (0.3%)
Pneumothorax	1/373 (0.3%)		0/377 (0%)
Pulmonary oedema	0/373 (0%)		1/377 (0.3%)
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome	0/373 (0%)		7/377 (1.9%)
Intertrigo	0/373 (0%)		1/377 (0.3%)
Surgical and medical procedures
Surgery	0/373 (0%)		1/377 (0.3%)
Uterine dilation and curettage	1/373 (0.3%)		0/377 (0%)
Vascular disorders
Deep vein thrombosis	1/373 (0.3%)		0/377 (0%)
Embolism	1/373 (0.3%)		0/377 (0%)
Hypertension	0/373 (0%)		1/377 (0.3%)
Jugular vein thrombosis	1/373 (0.3%)		0/377 (0%)
Phlebitis	0/373 (0%)		1/377 (0.3%)
Subclavian vein thrombosis	1/373 (0.3%)		0/377 (0%)
Superior vena caval occlusion	0/373 (0%)		1/377 (0.3%)
Other (Not Including Serious) Adverse Events
	Docetaxel		DOXIL+Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	340/373 (91.2%)		359/377 (95.2%)
Blood and lymphatic system disorders
Anaemia	62/373 (16.6%)		75/377 (19.9%)
Febrile neutropenia	14/373 (3.8%)		19/377 (5%)
Leukopenia	99/373 (26.5%)		126/377 (33.4%)
Neutropenia	241/373 (64.6%)		244/377 (64.7%)
Cardiac disorders
Tachycardia	14/373 (3.8%)		21/377 (5.6%)
Gastrointestinal disorders
Constipation	18/373 (4.8%)		13/377 (3.4%)
Diarrhoea	42/373 (11.3%)		56/377 (14.9%)
Mucositis/stomatitis	53/373 (14.2%)		195/377 (51.7%)
Nausea	80/373 (21.4%)		105/377 (27.9%)
Vomiting	35/373 (9.4%)		38/377 (10.1%)
General disorders
Asthenia	72/373 (19.3%)		110/377 (29.2%)
Fatigue	56/373 (15%)		78/377 (20.7%)
Oedema peripheral	34/373 (9.1%)		17/377 (4.5%)
Pyrexia	31/373 (8.3%)		59/377 (15.6%)
Infections and infestations
Respiratory tract infection	12/373 (3.2%)		21/377 (5.6%)
Investigations
Alanine aminotransferase increased	29/373 (7.8%)		31/377 (8.2%)
Aspartate aminotransferase increased	31/373 (8.3%)		26/377 (6.9%)
Weight decreased	6/373 (1.6%)		18/377 (4.8%)
Metabolism and nutrition disorders
Anorexia	21/373 (5.6%)		33/377 (8.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	25/373 (6.7%)		26/377 (6.9%)
Bone pain	26/373 (7%)		12/377 (3.2%)
Myalgia	33/373 (8.8%)		32/377 (8.5%)
Nervous system disorders
Dizziness	12/373 (3.2%)		18/377 (4.8%)
Dysgeusia	22/373 (5.9%)		10/377 (2.7%)
Headache	21/373 (5.6%)		39/377 (10.3%)
Peripheral neuropathy	68/373 (18.2%)		78/377 (20.7%)
Respiratory, thoracic and mediastinal disorders
Cough	23/373 (6.2%)		23/377 (6.1%)
Dyspnoea	40/373 (10.7%)		29/377 (7.7%)
Skin and subcutaneous tissue disorders
Alopecia	169/373 (45.3%)		181/377 (48%)
Erythema	6/373 (1.6%)		17/377 (4.5%)
Nail disorder	26/373 (7%)		37/377 (9.8%)
Palmar-plantar erythrodysaesthesia syndrome	5/373 (1.3%)		229/377 (60.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission. Expedited reviews will be arranged if needed. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days to allow for filing of a patent application. The sponsor will not mandate modifications to scientific content and does not have the right to suppress information.