Standard Versus Continuous Capecitabine in Advanced Breast Cancer
Standard Versus Continuous Capecitabine in Advanced Breast Cancer
Capecitabine is active in metastatic breast cancer but the conventional schedule (1250
 mg/m2/12 hr 2 weeks on, one week off) produces grade 2 or greater hand and foot syndrome in
 up to 50% of patients leading to those reductions. There are theoretical reasons to
 administer S-phase specific agents in continuous, protracted rather than intermittent
 schedules. The investigators study compares the standard schedule (1250 mg/m2/12 hr 2 weeks
 on, one week off) with a continuous administration schedule (800 mg/m2/12hr). The latter
 administer approximately the same cumulative dose of capecitabine as the standard schedule.
 The study hypothesis is that grade 2 or greater hand and foot syndrome will be reduced from
 50% (standard arm) to 20% (experimental arm). The investigators assume similar antitumor
 activity in both arms.
Capecitabine is active in metastatic breast cancer but the conventional schedule (1250
 mg/m2/12 hr 2 weeks on, one week off) produces grade 2 or greater hand and foot syndrome in
 up to 50% of patients leading to those reductions. Some authors have tested continuous
 administration schedules of capecitabine, showing better tolerance and apparently similar
 antitumor activity. Capecitabine is a pro-drug of 5-FU and mimics an i.v. continuous infusion
 administration of this antimetabolite. On the other hand, there are theoretical reasons to
 administer S-phase specific agents in continuous, protracted rather than intermittent
 schedules. Our study compares the standard schedule(1250 mg/m2/12 hr 2 weeks on, one week
 off)with a continuous administration schule (800 mg/m2/12hr). The latter schedule administer
 approximately the same cumulative dose of capecitabine as the standard one. The study
 hypothesis is that grade 2 or greater hand and foot syndrome will be reduced from 50%
 (standard arm) to 20% (experimental arm). The investigators assume similar antitumor activity
 in both arms.
Inclusion Criteria

 1. Patients diagnosed with metastatic breast cancer

 2. Patients that either have received previous treatment with anthracyclines and/or
 taxanes or not (either as advance or in metastatic disease).

 3. The patient is ambulatory with a functional ECOG < 2 status (see Appendix 2).

 4. Patient presents, at least one lesion measurable according to RECIST criteria (see
 Appendix 3)

 5. Patients with a life expectancy of at least 3 months.

 6. Patients that agree to and are able to fulfill the requirements of the whole protocol
 through the whole study.

 Exclusion criteria:

 1. Patients that have previously shown unexpected severe reactions to therapy with
 fluoropyrimidines or with a known sensitivity to 5-fluorouracile.

 2. Patients previously treated with capecitabine.

 3. Patients with organ transplants.

 4. Other diseases or severe affections:

 1. Patients with previous convulsions, central nervous system diseases or
 psychiatric diseases, including dementia, that the investigator might consider
 clinically significant and which adversely affect therapeutic compliance.

 2. Patients with severe intellectual impairment, unable to carry out basic daily
 routines and established depression.

 3. Clinical significant cardiac disease (e. g. . congestive heart failure,
 symptomatic coronary artery disease and cardiac arrhythmia not fully controlled
 with medication) or myocardial infarction within the last 12 months.

 4. Severe renal impairment (baseline creatinine clearance < 30 ml/min)

 5. Patients with signs of metastasis in the CNS. Patients with a history of uncontrolled
 convulsions, central nervous system disorders or psychiatric disability judged by the
 investigator to be clinically significant precluding informed consent or interfering
 with compliance for oral drug intake should be excluded.

 6. Patients with an active infection.

 7. Patients with a history of other neoplasias during the previous five years, except for
 basal cell skin cancer or cervical cancer in situ, both cured.

 8. Patients showing the following laboratory values:

 1. Neutrophil count < 555 x 109/l

 2. Platelet count< 100 x 109/l

 3. Serum creatinine > 1,5 x upper normality limit

 4. seric bilirubin > 2,0 x upper normality limit

 5. ALAT, ASAT > 2,5 x upper normality limit or > 5 x upper normality limit in case
 of liver metastases

 6. Alkaline phosphatase > 2,5 x upper normality limit > 5 x upper normality limit in
 case of liver metastases o > 10 x upper normality limit in case of bone
 metastases.

 9. Patients under radiotherapy four weeks prior to the initiation of the study treatment,
 or under previous radiotherapy on the marker lesions be measured during the study (new
 marker lesions that appear in previously irradiated areas are accepted) or patients
 who are receiving programmed radiotherapy.

 10. Patients under major surgery within 4 weeks prior to study treatment or who have not
 completely recovered from the effects of major surgery.

 11. Patients who lack upper gastrointestinal tract physical integrity or with
 malabsorption syndrome.

 12. Patients who have received more than two cycles of chemotherapy for the metastatic
 disease.

 13. Patients Her2 + per FISH ó +++ Immunohistochemistry