Maintenance Treatment With Capecitabine Versus Observation in Breast Cancer Patients

• Sponsor: Spanish Breast Cancer Research Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00130533
• Collaborator: Hoffmann-La Roche (Industry), IBEROAMERICAN COALITION FOR BREAST ONCOLOGY RESEARCH (CIBOMA) (Other)
• Enrollment: 876
• Locations: 48
• Arms: 2
• Actual Duration (Months): 133.6
• Patients Per Site: 18.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a prospective, open-label, randomized phase III study assessing adjuvant capecitabine after standard chemotherapy for patients with early triple negative breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Capecitabine	Phase 3

Detailed Description

Patients will be stratified as per investigational site, previous adjuvant chemotherapy (anthracyclines versus anthracyclines plus taxanes), and number of affected axillary lymph nodes (0, 1-3, >= 4). Node negative patients must present a tumour size > 2 cm to be eligible. At least 6 lymph nodes must be analysed to confirm the number of affected nodes. Patients will be randomised to receive: 8 courses of capecitabine 1000 mg/m2 by mouth, twice a day (p.o. bid) for 14 days, followed by a 7 day rest versus observation.

Tissue samples must be analysed by a central laboratory, to confirm estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor-2 (HER2), cytokeratins (CK) 5/6 and epidermal growth factor receptor (EGFR) status.

The following data were obtained from the database of the "El Alamo" project. One thousand six hundred and twenty-seven (1,627) in total were considered during the years 1990 to 1997. The population is formed of patients with operable breast cancer, with surgery, positive nodes, and negative hormone receptors, or negative nodes, negative hormone receptors and T2-3 tumors.

For these patient groups, estimated 5-year disease-free survival is 64.72%. Assuming an exponential distribution, the aim is to detect an increase of 64.72% to 73.7% in 5 years Disease Free survival rate corresponds to a Hazard Ratio of 0.701 and a risk reduction of about 30%, with a power of 80% using a two-tailed log-rank test at 0.05 and whereas 4 years of recruitment period and 3 years of follow-up period. We would need 255 events, 834 patients without considering any dropouts.

Considering a drop-out rate of 5% post-randomization, the final sample size will be 876 patients, 438 per treatment arm.

The sample size calculation was performed by the program package "EAST" version 5.2.

Study Design

• Study Type: Interventional
• Actual Enrollment: 876 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Multicenter, Open-label, Randomized Phase III to Evaluate Efficacy of Maintenance Treatment With Capecitabine Following Standard Adjuvant Chemotherapy in Operable Triple Negative Breast Cancer Patients
• Actual Study Start Date: Jan 1, 2006
• Actual Primary Completion Date: Feb 17, 2017
• Actual Study Completion Date: Feb 17, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Xeloda (capecitabine) 1000 mgrs/m2 twice a day, tablets, 8 cycles	Drug: Capecitabine; Other Names: Xeloda
No Intervention: Observation Observation. No intervention.

Outcome Measures

Primary Outcome Measures

1. Disease Free Survival (DFS) Events [5 years]

   DFS was measured from the date of randomization assignment in the intent to treat (ITT) population to loco-regional or distant recurrence, second primary malignancy or death date, whichever occurred first.

Secondary Outcome Measures

1. Disease Free Survival (DFS) Events by Phenotype [5 years]

   DFS was measured from the date of randomization assignment in the intent to treat (ITT) population to loco-regional or distant recurrence, second primary malignancy or death date, whichever occurred first.

2. Overall Survival (OS) Event [5 years]

   OS event is defined as the death from any cause.

3. The Number of Participants Who Experienced Adverse Events (AE) [5 years]

   Safety will be assessed by standard clinical and laboratory tests (haematology, serum chemistry). AE grade were defined by the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Written informed consent.

• Histological diagnoses of operable invasive adenocarcinoma of the breast (T1-T3). Tumours must be HER2 negative. Time window between end of adjuvant chemotherapy and study randomization must be less than 8 weeks. In patients receiving adjuvant radiotherapy, time window allowed between last session and randomisation is 4 weeks.

• Surgery must consist of mastectomy or conservative surgery with axillary lymph node dissection. Margins free of disease and ductal carcinoma in-situ (DCIS) are required. Lobular carcinoma is not considered a positive margin.

• Node negative patients with tumour size > 2 cm.

• Positive axillary lymph nodes defined as at least 1 out of 6 nodes with presence of disease. If sentinel node technique is used, sentinel node can be the only node affected. Patients belonging to the following classifications are eligible: pN1a (Metastases in 1-3 axillary lymph nodes, at least one metastasis greater than 2.0 mm), pN2a (Metastases in 4-9 axillary lymph nodes (at least one tumor deposit greater than 2 mm)), pN3a (Metastases in 10 or more axillary lymph nodes [at least one tumor deposit greater than 2 mm]; or metastases to the infraclavicular [level III axillary lymph] nodes).

• Status of hormone receptors in primary tumour. Negative results must be available before the end of adjuvant chemotherapy.

• Patients must not present evidence of metastatic disease.

• Negative status of HER2 in primary tumour, known before randomization.

• Adjuvant chemotherapy consisting of a minimum of 6 courses with anthracyclines and/or taxanes.

• Age >= 18 and <= 70 years old.

• Performance status (Karnofsky index) >= 80.

• Laboratory results (within 14 days prior to randomization):

• Hematology:

• neutrophils >= 1.5 x 10e9/l;

• platelets >= 100x 10e9/l;

• hemoglobin >= 10 mg/dl

• Hepatic function:

• total bilirubin <= 1 upper normal limit (UNL);

• Aspartate aminotransferase (AST or SGOT) and Alanine aminotransferase (ALT or SGPT) <= 2.5 UNL;

• alkaline phosphatase <= 2.5 UNL.

• If values of SGOT and SGPT > 1.5 UNL are associated to alkaline phosphatase > 2.5 UNL, patient is not eligible.

• Renal Function:

• creatinine <= 175 µmol/l (2 mg/dl).

• creatinine clearance >= 60 ml/min.

• Pharmacogenetics:

• one blood sample is needed for single nucleotide polymorphism (SNP) assessment.

• Patients able to comply with treatment and study follow-up.

• Negative pregnancy test done in the 14 previous days to randomization.

Exclusion Criteria:

• Prior therapy with anthracyclines or taxanes (paclitaxel or docetaxel) for any malignancy.

• Pregnant or lactating women. Adequate contraceptive methods must be used during chemotherapy and hormone therapy treatments. Negative pregnancy test in the 14 previous days to randomization.

• Bilateral invasive breast cancer.

• Any T4 or M1 tumour.

• Axillary lymph nodes: patients belonging to the following classifications are excluded: pN1b (Metastases in internal mammary nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected), pN1c (Metastases in 1-3 axillary lymph nodes and in internal mammary lymph nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected), pN2b (Metastases in clinically detected internal mammary lymph nodes in the absence of axillary lymph node metastases), pN3b (Metastases in clinically detected ipsilateral internal mammary lymph nodes in the presence of one or more positive axillary lymph nodes; or in more than three axillary lymph nodes and in internal mammary lymph nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected), pN3c (Metastases in ipsilateral supraclavicular lymph nodes).

• Any other serious medical pathology, such as congestive heart failure, unstable angina, history of myocardial infarction during the previous year, uncontrolled hypertension or high risk arrhythmias.

• History of neurological or psychiatric disorders, which could preclude the patients to free informed consent.

• Active uncontrolled infection.

• Active peptic ulcer, unstable diabetes mellitus.

• Previous or current history of neoplasms different to breast cancer, except for skin carcinoma, cervical in situ carcinoma, or any other tumour curatively treated and without recurrence in the last 10 years; ductal in situ carcinoma in the same breast; lobular in situ carcinoma.

• History of hypersensitivity to capecitabine, fluorouracil.

• Patients lacking physical integrity of upper gastrointestinal tract or with history of bad absorption syndrome.

• History of dihydropyrimidine dehydrogenase (DPD) deficiency.

• Anticoagulant treatment with coumadin anticoagulants.

• Current treatment with sorivudine or its chemical family.

• Concomitant treatment with other investigational products. Participation in other clinical trials with a non-marketed drug in the 30 previous days before randomization.

• Concomitant treatment with other therapy for cancer.

• Males.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital General Universitario de Elche	Elche	Alicante	Spain	03203
2	Instituto Catalán de Oncología de L'Hospitalet	L'Hospitalet De Llobregat	Barcelona	Spain	08908
3	Corporació Sanitaria Parc Taulí	Sabadell	Barcelona	Spain	08208
4	Hospital del Espíritu Santo	Santa Coloma De Gramenet	Barcelona	Spain	08923
5	Consorci Sanitari de Terrassa	Terrassa	Barcelona	Spain	08227
6	Hospital Universitario Marqués de Valdecilla	Santander	Cantabria	Spain	39008
7	Hospital Provincial de Castellón	Castellón De La Plana	Castellón	Spain	12002
8	Hospital General de Jerez	Jerez De La Frontera	Cádiz	Spain	11407
9	Onkologikoa	Donostia-San Sebastián	Guipúzcoa	Spain	20012
10	Hospital de Donostia	Donostia-San Sebastián	Guipúzcoa	Spain	20014
11	Hospital de Barbastro	Barbastro	Huesca	Spain	22300
12	Hospital Insular de Las Palmas de Gran Canaria	Las Palmas De Gran Canaria	Las Palmas	Spain	35016
13	Hospital Universitario Fundación Alcorcón	Alcorcón	Madrid	Spain	28922
14	Coalición Iberoamericana de Investigación en Oncología Mamaria (CIBOMA)	San Sebastián de los Reyes	Madrid	Spain	28703
15	Complejo Hospitalario Universitario de Vigo	Vigo	Pontevedra	Spain	36312
16	Complejo Hospitalario Universitario A Coruña	A Coruña		Spain	15006
17	Centro Oncológico de Galicia	A Coruña		Spain	15009
18	Hospital Universitario General de Alicante	Alicante		Spain	03010
19	Hospital del Mar	Barcelona		Spain	08003
20	Hospital Santa Creu i Sant Pau	Barcelona		Spain	08025
21	Hospital Clinic i Provincial	Barcelona		Spain	08036
22	Hospital Universitario Germans Trias i Pujol	Barcelona		Spain	08916
23	Hospital Universitario General Yagüe	Burgos		Spain	09006
24	Hospital Universitario Puerta del Mar	Cádiz		Spain	11009
25	Hospital Universitario Reina Sofía	Córdoba		Spain	14004
26	Hospital General Universitario de Guadalajara	Guadalajara		Spain	19002
27	Complejo Hospitalario de Jaén	Jaén		Spain	23007
28	Hospital Universitario Arnau de Vilanova de Lleida	Lleida		Spain	25198
29	Hospital Universitario La Princesa	Madrid		Spain	28006
30	Hospital Universitario 12 de Octubre	Madrid		Spain	28021
31	Hospital Ruber Internacional	Madrid		Spain	28034
32	Hospital Clínico Universitario San Carlos	Madrid		Spain	28040
33	Hospital de Madrid Norte Sanchinarro (CIOCC)	Madrid		Spain	28050
34	Hospital Universitario Virgen de la Arrixaca	Madrid		Spain	30120
35	Hospital General Universitario Morales Meseguer	Murcia		Spain	30008
36	Hospital Regional Universitario Carlos Haya	Málaga		Spain	29010
37	Complejo Hospitalario de Ourense	Ourense		Spain	32005
38	Hospital Clínico Universitario de Salamanca	Salamanca		Spain	37007
39	Hospital Universitario Nuestra Señora de Candelaria	Santa Cruz De Tenerife		Spain	38010
40	Hospital Universitario Virgen del Rocío	Sevilla		Spain	41013
41	Hospital Universitario de Valme	Sevilla		Spain	41014
42	Hospital Virgen de la Salud	Toledo		Spain	45004
43	Instituto Valenciano de Oncología	Valencia		Spain	46009
44	Hospital Clínico Universitario de Valencia	Valencia		Spain	46010
45	Hospital General Universitario de Valencia	Valencia		Spain	46014
46	Hospital Provincial de Zamora "Rodríguez Chamorro"	Zamora		Spain	49021
47	Hospital Clínico Universitario de Zaragoza "Lozano Blesa"	Zaragoza		Spain	50009
48	Hospital Universitario Miguel Servet	Zaragoza		Spain	50009

Sponsors and Collaborators

• Spanish Breast Cancer Research Group
• Hoffmann-La Roche
• IBEROAMERICAN COALITION FOR BREAST ONCOLOGY RESEARCH (CIBOMA)

Investigators

• Principal Investigator: Study Principal Investigator, Hospital Clínico Universitario de Valencia

Study Documents (Full-Text)

• Study Protocol - Sep 16, 2009
• Statistical Analysis Plan - May 1, 2010

More Information

Additional Information:

• Sponsor's web
• Spanish Breast Cancer Research Group (GEICAM) is a Spanish Breast Cancer Research Group

Publications

None provided.

• Responsible Party: Spanish Breast Cancer Research Group
• ClinicalTrials.gov Identifier: NCT00130533
• Other Study ID Numbers: CIBOMA 2004-01; 2005-002838-36
• First Posted: Aug 15, 2005
• Last Update Posted: Oct 25, 2019
• Last Verified: Oct 1, 2019

• Keywords provided by Spanish Breast Cancer Research Group: Triple-Negative Early Breast Cancer; Maintenance Adjuvant Chemotherapy; Capecitabine; Basal-like genotype; Triple-Negative
• Additional relevant MeSH terms: Breast Neoplasms; Capecitabine

Study Results

Participant Flow

Recruitment Details	Between October 2006 and September 2011, 876 patients were recruited, across 80 institutions in 8 countries (Spain, Brazil, Chile, Colombia, Ecuador, Mexico, Peru, and Venezuela)

Arm/Group Title	Xeloda (Capecitabine)	Observation
Arm/Group Description	1000 mgrs/m2 twice a day, tablets, 8 cycles Capecitabine	Observation. No intervention.
Period Title: Overall Study
STARTED	448	428
COMPLETED	337	398
NOT COMPLETED	111	30

Baseline Characteristics

Arm/Group Title	Xeloda (Capecitabine)	Observation	Total
Arm/Group Description	1000 mgrs/m2 twice a day, tablets, 8 cycles Capecitabine	Observation. No intervention.	Total of all reporting groups
Overall Participants	448	428	876
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	50	49	49
Sex: Female, Male (Count of Participants)
Female	448 100%	428 100%	876 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	313 69.9%	309 72.2%	622 71%
Hispanic	107 23.9%	97 22.7%	204 23.3%
Black	16 3.6%	11 2.6%	27 3.1%
Other	12 2.7%	11 2.6%	23 2.6%
Region of Enrollment (participants) [Number]
Spain	272 60.7%	260 60.7%	532 60.7%
Brazil	71 15.8%	68 15.9%	139 15.9%
Mexico	61 13.6%	52 12.1%	113 12.9%
Chile	19 4.2%	23 5.4%	42 4.8%
Peru	7 1.6%	12 2.8%	19 2.2%
Ecuador	9 2%	9 2.1%	18 2.1%
Colombia	6 1.3%	3 0.7%	9 1%
Venezuela	3 0.7%	1 0.2%	4 0.5%
Karnofsky Index Performance Status (Count of Participants)
80	8 1.8%	17 4%	25 2.9%
90	57 12.7%	67 15.7%	124 14.2%
100	383 85.5%	344 80.4%	727 83%
Menopausal status at diagnosis (Count of Participants)
Premenopausal	136 30.4%	140 32.7%	276 31.5%
Postmenopausal	312 69.6%	288 67.3%	600 68.5%
Histologic type (Count of Participants)
Invasive ductal carcinoma	395 88.2%	369 86.2%	764 87.2%
Invasive lobular carcinoma	9 2%	10 2.3%	19 2.2%
Other	44 9.8%	49 11.4%	93 10.6%
Histologic grade (Count of Participants)
Grade 1	15 3.3%	12 2.8%	27 3.1%
Grade 2	82 18.3%	81 18.9%	163 18.6%
Grade 3	323 72.1%	299 69.9%	622 71%
Unknown	28 6.3%	36 8.4%	64 7.3%
Phenotype by immunohistochemistry (IHC) (Count of Participants)
Basal	319 71.2%	309 72.2%	628 71.7%
Non-basal	129 28.8%	119 27.8%	248 28.3%
Stage at diagnosis (Count of Participants)
Stage I	62 13.8%	74 17.3%	136 15.5%
Stage II	270 60.3%	271 63.3%	541 61.8%
Stage III	106 23.7%	80 18.7%	186 21.2%
Unknown	10 2.2%	3 0.7%	13 1.5%
Nodal status (Count of Participants)
Negative	244 54.5%	242 56.5%	486 55.5%
1-3 positive nodes	121 27%	124 29%	245 28%
≥4 positive nodes	77 17.2%	61 14.3%	138 15.8%
Missing data	6 1.3%	1 0.2%	7 0.8%
Type of prior Chemotherapy (Count of Participants)
Adjuvant (only)	353 78.8%	352 82.2%	705 80.5%
Neoadjuvant (+/- adjuvant)	89 19.9%	75 17.5%	164 18.7%
Missing data	6 1.3%	1 0.2%	7 0.8%
Chemotherapy regimens (Count of Participants)
Anthracyclines-based	147 32.8%	138 32.2%	285 32.5%
Anthracyclines and taxanes-based	301 67.2%	290 67.8%	591 67.5%
Breast surgery (Count of Participants)
Conservative	237 52.9%	242 56.5%	479 54.7%
Mastectomy	205 45.8%	185 43.2%	390 44.5%
Missing data	6 1.3%	1 0.2%	7 0.8%
Axillary surgery (Count of Participants)
sentinel lymph node biopsy (SLNB)	99 22.1%	122 28.5%	221 25.2%
axillary lymph node dissection +/- SLNB	349 77.9%	306 71.5%	655 74.8%
Radiation therapy (Count of Participants)
Yes	352 78.6%	346 80.8%	698 79.7%
No	91 20.3%	81 18.9%	172 19.6%
Unknown	5 1.1%	1 0.2%	6 0.7%

Outcome Measures

1. Primary Outcome

Title	Disease Free Survival (DFS) Events
Description	DFS was measured from the date of randomization assignment in the intent to treat (ITT) population to loco-regional or distant recurrence, second primary malignancy or death date, whichever occurred first.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Xeloda (Capecitabine)	Observation
Arm/Group Description	1000 mgrs/m2 twice a day, tablets, 8 cycles Capecitabine	Observation. No intervention.
Measure Participants	448	428
Count of Participants [Participants]	105 23.4%	120 28%

2. Secondary Outcome

Title	Disease Free Survival (DFS) Events by Phenotype
Description	DFS was measured from the date of randomization assignment in the intent to treat (ITT) population to loco-regional or distant recurrence, second primary malignancy or death date, whichever occurred first.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Xeloda (Capecitabine)	Observation
Arm/Group Description	1000 mgrs/m2 twice a day, tablets, 8 cycles Capecitabine	Observation. No intervention.
Measure Participants	105	120
Basal Phenotype	84 18.8%	86 20.1%
Non basal Phenotype	21 4.7%	34 7.9%

3. Secondary Outcome

Title	Overall Survival (OS) Event
Description	OS event is defined as the death from any cause.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Xeloda (Capecitabine)	Observation
Arm/Group Description	1000 mgrs/m2 twice a day, tablets, 8 cycles Capecitabine	Observation. No intervention.
Measure Participants	448	428
Count of Participants [Participants]	71 15.8%	73 17.1%

4. Secondary Outcome

Title	The Number of Participants Who Experienced Adverse Events (AE)
Description	Safety will be assessed by standard clinical and laboratory tests (haematology, serum chemistry). AE grade were defined by the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events).
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

The analysis of toxicity was made in all study patients who had received at least 1 treatment cycle, or who had completed the observation period equivalent to 1 cycle.

Arm/Group Title	Xeloda (Capecitabine)	Observation
Arm/Group Description	1000 mgrs/m2 twice a day, tablets, 8 cycles Capecitabine	Observation. No intervention.
Measure Participants	436	425
Count of Participants [Participants]	416 92.9%	271 63.3%

Adverse Events

Time Frame	5 years
Arm/Group Title	Xeloda (Capecitabine)		Observation
Arm/Group Description	1000 mgrs/m2 twice a day, tablets, 8 cycles Capecitabine		Observation. No intervention.
All Cause Mortality
	Xeloda (Capecitabine)		Observation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	71/448 (15.8%)		73/428 (17.1%)
Serious Adverse Events
	Xeloda (Capecitabine)		Observation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/436 (5.3%)		6/425 (1.4%)
Blood and lymphatic system disorders
Neutropenia G 3; Leucopenia G2	1/436 (0.2%)		0/425 (0%)
Hyperbilirrubinemia	1/436 (0.2%)		0/425 (0%)
Cardiac disorders
Supraventricular arrhythmia NOS	1/436 (0.2%)		0/425 (0%)
Heart failure	0/436 (0%)		1/425 (0.2%)
Infarction and cardiac arrest	0/436 (0%)		1/425 (0.2%)
Ischemia cardiac/Infarction	1/436 (0.2%)		0/425 (0%)
Coronary vasospam	1/436 (0.2%)		0/425 (0%)
Gastrointestinal disorders
Gastroenteritis and renal insuficience	1/436 (0.2%)		0/425 (0%)
Diarrhea	4/436 (0.9%)		0/425 (0%)
Pancreatitis	2/436 (0.5%)		0/425 (0%)
Mucositis Oral cavity and Pharynx	1/436 (0.2%)		0/425 (0%)
Diarrhea grade 2, Vomiting grade 2, Septic shock grade 5	1/436 (0.2%)		0/425 (0%)
Ulcer gastric	1/436 (0.2%)		0/425 (0%)
General disorders
Worsening of depressive syndrome	1/436 (0.2%)		0/425 (0%)
Dehydration	1/436 (0.2%)		0/425 (0%)
Febrile neutropenia, Diarrhea, Hand foot skin reaction, Acute renal failure	1/436 (0.2%)		0/425 (0%)
Infections and infestations
Infection with normal ANC ( Urinary)	1/436 (0.2%)		0/425 (0%)
Infection with unknown ANC pulmonary/upper respiratory - lung (pneumonia)	0/436 (0%)		1/425 (0.2%)
Pneumonia	1/436 (0.2%)		0/425 (0%)
Musculoskeletal and connective tissue disorders
Thorax and left arm pain	1/436 (0.2%)		0/425 (0%)
Showed lumbar column fracture(L4)	0/436 (0%)		1/425 (0.2%)
Nervous system disorders
CNS cerebrovascular ischemia	2/436 (0.5%)		0/425 (0%)
Hand-foot skin reaction	1/436 (0.2%)		0/425 (0%)
Pregnancy, puerperium and perinatal conditions
Positive pregnant test performed	0/436 (0%)		1/425 (0.2%)
Renal and urinary disorders
Right renal colic	1/436 (0.2%)		0/425 (0%)
Respiratory, thoracic and mediastinal disorders
Thoracic pain grade 2, disnea G-1	0/436 (0%)		1/425 (0.2%)
Surgical and medical procedures
Axillary nodular resection	1/436 (0.2%)		0/425 (0%)
Vascular disorders
Thrombosis/thrombus/embolism: venous thrombosis	1/436 (0.2%)		0/425 (0%)
Other (Not Including Serious) Adverse Events
	Xeloda (Capecitabine)		Observation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	416/436 (95.4%)		271/425 (63.8%)
Blood and lymphatic system disorders
LYMPHOPENIA	1/436 (0.2%)		0/425 (0%)
LYMPHOPENIA	3/436 (0.7%)		1/425 (0.2%)
LYMPHOPENIA	19/436 (4.4%)		6/425 (1.4%)
LYMPHOPENIA	40/436 (9.2%)		26/425 (6.1%)
LEUKOCYTES (TOTAL WBC)	1/436 (0.2%)		0/425 (0%)
LEUKOCYTES (TOTAL WBC)	54/436 (12.4%)		12/425 (2.8%)
LEUKOCYTES (TOTAL WBC)	81/436 (18.6%)		46/425 (10.8%)
NEUTROPHILS/GRANULOCYTES	8/436 (1.8%)		0/425 (0%)
NEUTROPHILS/GRANULOCYTES	50/436 (11.5%)		8/425 (1.9%)
NEUTROPHILS/GRANULOCYTES	67/436 (15.4%)		38/425 (8.9%)
HEMOGLOBIN	1/436 (0.2%)		0/425 (0%)
HEMOGLOBIN	19/436 (4.4%)		0/425 (0%)
HEMOGLOBIN	87/436 (20%)		27/425 (6.4%)
Gastrointestinal disorders
DIARRHEA	1/436 (0.2%)		0/425 (0%)
DIARRHEA	14/436 (3.2%)		0/425 (0%)
DIARRHEA	45/436 (10.3%)		2/425 (0.5%)
DIARRHEA	94/436 (21.6%)		4/425 (0.9%)
NAUSEA	4/436 (0.9%)		0/425 (0%)
NAUSEA	15/436 (3.4%)		0/425 (0%)
NAUSEA	84/436 (19.3%)		6/425 (1.4%)
General disorders
FATIGUE	13/436 (3%)		0/425 (0%)
FATIGUE	48/436 (11%)		10/425 (2.4%)
FATIGUE	111/436 (25.5%)		38/425 (8.9%)
Metabolism and nutrition disorders
BILIRUBIN	1/436 (0.2%)		0/425 (0%)
AST, SGOT	1/436 (0.2%)		0/425 (0%)
AST, SGOT	8/436 (1.8%)		0/425 (0%)
AST, SGOT	74/436 (17%)		23/425 (5.4%)
URIC ACID, SERUM-HIGH	0/436 (0%)		1/425 (0.2%)
URIC ACID, SERUM-HIGH	7/436 (1.6%)		4/425 (0.9%)
ALT, SGPT	1/436 (0.2%)		0/425 (0%)
ALT, SGPT	15/436 (3.4%)		1/425 (0.2%)
ALT, SGPT	69/436 (15.8%)		27/425 (6.4%)
Nervous system disorders
NEUROPATHY: SENSORY	3/436 (0.7%)		1/425 (0.2%)
NEUROPATHY: SENSORY	13/436 (3%)		3/425 (0.7%)
NEUROPATHY: SENSORY	50/436 (11.5%)		21/425 (4.9%)
Renal and urinary disorders
RENAL FAILURE	1/436 (0.2%)		0/425 (0%)
RENAL FAILURE	1/436 (0.2%)		0/425 (0%)
Reproductive system and breast disorders
IRREGULAR MENSES	57/436 (13.1%)		55/425 (12.9%)
IRREGULAR MENSES	7/436 (1.6%)		6/425 (1.4%)
IRREGULAR MENSES	5/436 (1.1%)		6/425 (1.4%)
Skin and subcutaneous tissue disorders
RASH: HAND-FOOT SKIN REACTION	82/436 (18.8%)		0/425 (0%)
RASH: HAND-FOOT SKIN REACTION	109/436 (25%)		1/425 (0.2%)
RASH: HAND-FOOT SKIN REACTION	115/436 (26.4%)		2/425 (0.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.