taxane and Diarrhea

Capecitabine is frequently used alone or combined with other chemotherapy agents for the treatment of metastatic breast cancer in relapsed patients.. The objective of this meta-analysis is to evaluate the effectiveness and safety of capecitabine monotherapy versus combination in the treatment of metastatic breast cancer patients pretreated with anthracycline and taxane.. Eligible randomized controlled trials examining the efficacy and safety of capecitabine alone compared to capecitabine combination were systematically searched. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and grades 3-4 drug-related adverse events were the outcomes assessed.. A total of 6,714 patients of 9 trials were involved in the pooled analysis. Our findings demonstrated that capecitabine combination is significantly superior to capecitabine monotherapy in improving PFS (hazard ratio [HR] 1.32, 95% CI 1.13-1.54, p < 0.0001) and ORR (risk ratio [RR] 0.67, 95% CI 0.54-0.83, p < 0.001), but it was insignificant in OS (HR 1.09, 95% CI 0.98-1.22, p = 0.12). On the other hand, the incidence of non-hematological adverse events such as hand-foot syndrome and diarrhea was lower in capecitabine combination compared to capecitabine monotherapy.. Capecitabine-based combination chemotherapy showed superiority over capecitabine monotherapy in terms of PFS and ORR, with no significant difference in OS. Non-hematological adverse effects such as hand-foot syndrome were fewer with a combination regimen. However, hematological adverse events were fewer with capecitabine monotherapy regimen.

Topics: Anthracyclines; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Capecitabine; Diarrhea; Female; Hand-Foot Syndrome; Humans; Middle Aged; Progression-Free Survival; Randomized Controlled Trials as Topic; Survival Rate; Taxoids; Treatment Outcome

To assess whether crofelemer would prevent chemotherapy-induced diarrhea (CID) diarrhea in patients with HER2-positive, any-stage breast cancer receiving trastuzumab (H), pertuzumab (P), and a taxane (T; docetaxel or paclitaxel), with/without carboplatin (C; always combined with docetaxel rather than paclitaxel).. Patients scheduled to receive ≥ 3 consecutive TCHP/THP cycles were randomized to crofelemer 125 mg orally twice daily during chemotherapy cycles 1 and 2 or no scheduled prophylactic medication (control). All received standard breakthrough antidiarrheal medication (BTAD) as needed. The primary endpoint was incidence of any-grade CID for ≥ 2 consecutive days. Secondary endpoints were incidence of all-grade and grade 3/4 CID by cycle/stratum; time to onset and duration of CID; stool consistency; use of BTAD; and quality of life (Functional Assessment of Chronic Illness Therapy for Patients With Diarrhea [FACIT-D] score).. Fifty-one patients were randomized to crofelemer (n = 26) or control (n = 25). There was no statistically significant difference between arms for the primary endpoint; however, incidence of grade ≥ 2 CID was reduced with crofelemer vs control (19.2% vs 24.0% in cycle 1; 8.0% vs 39.1%, in cycle 2). Patients receiving crofelemer were 1.8 times more likely to see their diarrhea resolved and had less frequent watery diarrhea.. Despite the choice of primary endpoint being insensitive, crofelemer reduced the incidence and severity of CID in patients with HER2-positive breast cancer receiving P-based therapy. These data are supportive of further testing of crofelemer in CID.. Clinicaltrials.gov, NCT02910219, prospectively registered September 21, 2016.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Diarrhea; Docetaxel; Female; Humans; Paclitaxel; Quality of Life; Receptor, ErbB-2; Taxoids; Trastuzumab

The antibody-drug conjugate trastuzumab emtansine is indicated for the treatment of patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. Approval of this drug was based on progression-free survival and interim overall survival data from the phase 3 EMILIA study. In this report, we present a descriptive analysis of the final overall survival data from that trial.. EMILIA was a randomised, international, open-label, phase 3 study of men and women aged 18 years or older with HER2-positive unresectable, locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane. Enrolled patients were randomly assigned (1:1) via a hierarchical, dynamic randomisation scheme and an interactive voice response system to trastuzumab emtansine (3·6 mg/kg intravenously every 3 weeks) or control (capecitabine 1000 mg/m. Between Feb 23, 2009, and Oct 13, 2011, 991 eligible patients were enrolled and randomly assigned to either trastuzumab emtansine (n=495) or capecitabine and lapatinib (control; n=496). In this final descriptive analysis, median overall survival was longer with trastuzumab emtansine than with control (29·9 months [95% CI 26·3-34·1] vs 25·9 months [95% CI 22·7-28·3]; hazard ratio 0·75 [95% CI 0·64-0·88]). 136 (27%) of 496 patients crossed over from control to trastuzumab emtansine after the second interim overall survival analysis (median follow-up duration 24·1 months [IQR 19·5-26·1]). Of those patients originally randomly assigned to trastuzumab emtansine, 254 (51%) of 495 received capecitabine and 241 [49%] of 495 received lapatinib (separately or in combination) after study drug discontinuation. In the safety population (488 patients treated with capecitabine plus lapatinib, 490 patients treated with trastuzumab emtansine), fewer grade 3 or worse adverse events occurred with trastuzumab emtansine (233 [48%] of 490) than with capecitabine plus lapatinib control treatment (291 [60%] of 488). In the control group, the most frequently reported grade 3 or worse adverse events were diarrhoea (103 [21%] of 488 patients) followed by palmar-plantar erythrodysaesthesia syndrome (87 [18%]), and vomiting (24 [5%]). The safety profile of trastuzumab emtansine was similar to that reported previously; the most frequently reported grade 3 or worse adverse events in the trastuzumab emtansine group were thrombocytopenia (70 [14%] of 490), increased aspartate aminotransferase levels (22 [5%]), and anaemia (19 [4%]). Nine patients died from adverse events; five of these deaths were judged to be related to treatment (two in the control group [coronary artery disease and multiorgan failure] and three in the trastuzumab emtansine group [metabolic encephalopathy, neutropenic sepsis, and acute myeloid leukaemia]).. This descriptive analysis of final overall survival in the EMILIA trial shows that trastuzumab emtansine improved overall survival in patients with previously treated HER2-positive metastatic breast cancer even in the presence of crossover treatment. The safety profile was similar to that reported in previous analyses, reaffirming trastuzumab emtansine as an efficacious and tolerable treatment in this patient population.. F Hoffmann-La Roche/Genentech.

Topics: Ado-Trastuzumab Emtansine; Adult; Aged; Aged, 80 and over; Anemia; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aspartate Aminotransferases; Breast Neoplasms; Breast Neoplasms, Male; Bridged-Ring Compounds; Capecitabine; Diarrhea; Disease-Free Survival; Female; Hand-Foot Syndrome; Humans; Lapatinib; Male; Maytansine; Middle Aged; Quinazolines; Receptor, ErbB-2; Response Evaluation Criteria in Solid Tumors; Retreatment; Survival Rate; Taxoids; Thrombocytopenia; Trastuzumab; Vomiting; Young Adult

In the randomised, parallel assignment, open-label, phase 3 TH3RESA study, progression-free survival was significantly longer with trastuzumab emtansine versus treatment of physician's choice in previously treated patients with HER2-positive advanced breast cancer. We report results from the final overall survival analysis of the TH3RESA trial.. Eligible patients for the TH3RESA trial were men and women (aged ≥18 years) with centrally confirmed HER2-positive advanced breast cancer previously treated with both trastuzumab and lapatinib (advanced setting) and a taxane (any setting) and with progression on two or more HER2-directed regimens in the advanced setting. Patients had to have an Eastern Cooperative Oncology Group performance status of 0-2, left ventricular ejection fraction of at least 50%, and adequate organ function. Patients were randomly assigned (2:1) by an interactive voice and web response system with permuted block randomisation in blocks of six to receive trastuzumab emtansine (3·6 mg/kg intravenously every 21 days) or treatment of physician's choice administered per local practice. Randomisation was stratified by world region, number of previous regimens for advanced breast cancer, and presence of visceral disease. On Sept 12, 2012, the study protocol was amended to allow patients with disease progression to crossover from treatment of physician's choice to trastuzumab emtansine. The coprimary endpoints for TH3RESA were investigator-assessed progression-free survival and overall survival in the intention-to-treat population. We report results from a preplanned second interim analysis of overall survival, which was planned for when approximately 67% (n=330) of 492 expected deaths had occurred. This study is registered with ClinicalTrials.gov, number NCT01419197.. Between Sept 14, 2011, and Nov 19, 2012, 602 patients were enrolled from 146 centres in 22 countries and randomly assigned to trastuzumab emtansine (n=404) or treatment of physician's choice (n=198). At data cutoff (Feb 13, 2015), 93 (47%) of 198 patients in the physician's choice group had crossed over to trastuzumab emtansine. Overall survival was significantly longer with trastuzumab emtansine versus treatment of physician's choice (median 22·7 months [95% CI 19·4-27·5] vs 15·8 months [13·5-18·7]; hazard ratio 0·68 [95% CI 0·54-0·85]; p=0·0007). As the stopping boundary for overall survival was crossed, this overall survival analysis serves as the final and confirmatory analysis of overall survival and the study was terminated according to the protocol. The incidence of grade 3 or worse adverse events was 161 (40%) of 403 patients in the trastuzumab emtansine group and 87 (47%) of 184 patients in the treatment of physician's choice group. Of the most common grade 3 or worse adverse events (affecting ≥2% of patients in either group), those with a 3% or greater difference in incidence between groups that were more frequent with treatment of physician's choice than with trastuzumab emtansine were diarrhoea (three [1%] of 403 patients in the trastuzumab emtansine group vs eight [4%] of 184 patients in the treatment of physician's choice group), neutropenia (ten [3%] vs 29 [16%]), and febrile neutropenia (one [<1%] vs seven [4%]); whereas those that were more frequent with trastuzumab emtansine were thrombocytopenia (24 [6%] of 403 patients vs five [3%] of 184 patients) and haemorrhage of any type (17 [4%] of 403 vs one [<1%] of 184). Serious adverse events were reported in 102 (25%) of 403 patients in the trastuzumab emtansine group and 41 (22%) of 184 in the physician's choice group. Deaths from adverse events were reported in three patients (2%) in the physician's choice group (of which one was judged to be treatment related) and nine (2%) in the trastuzumab emtansine group (of which three were judged to be treatment related).. In patients who had progressed on two or more HER2-directed regimens, trastuzumab emtansine treatment resulted in a significant improvement in overall survival versus treatment of physician's choice. These data further solidify the role of trastuzumab emtansine in the management of patients with previously treated HER2-positive advanced breast cancer, and validate HER2 as a therapeutic target even after multiple lines of previous therapy.. F Hoffman-La Roche/Genentech.

Topics: Ado-Trastuzumab Emtansine; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Breast Neoplasms, Male; Bridged-Ring Compounds; Chemotherapy-Induced Febrile Neutropenia; Diarrhea; Early Termination of Clinical Trials; Female; Hemorrhage; Humans; Lapatinib; Male; Maytansine; Middle Aged; Neoplasm Metastasis; Neutropenia; Practice Patterns, Physicians'; Quinazolines; Receptor, ErbB-2; Retreatment; Survival Rate; Taxoids; Thrombocytopenia; Trastuzumab

Sorafenib is a multikinase inhibitor with antiangiogenic/antiproliferative activity. In this randomized, double-blind, placebo-controlled phase III trial, we assessed first- or second-line capecitabine with sorafenib or placebo in patients with locally advanced/metastatic HER2-negative breast cancer resistant to a taxane and anthracycline and with known estrogen/progesterone receptor status.. Treatment with sorafenib with capecitabine, compared with capecitabine with placebo, did not prolong median PFS (5.5 vs. 5.4 months; hazard ratio [HR], 0.973; 95% confidence interval [CI], 0.779-1.217; P = .811) or overall survival (OS; 18.9 vs. 20.3 months; HR, 1.195; 95% CI, 0.943-1.513; P = .140); or enhance overall response rate (ORR; 13.5% vs. 15.5%; P = .515). Any grade toxicities (sorafenib vs. placebo) included palmar-plantar erythrodysesthesia syndrome (PPES; 79.2% vs. 59.6%), diarrhea (47.3% vs. 37.8%), mucosal inflammation (15.4% vs. 6.7%), and hypertension (26.2% vs. 5.6%). Grade 3/4 toxicities included PPES (15.4% vs. 7.1%), diarrhea (4.2% vs. 6.4%), and vomiting (3.5% vs. 0.7%).. The combination of sorafenib with capecitabine did not improve PFS, OS, or ORR in patients with HER2-negative advanced breast cancer. Rates of Grade 3 toxicities were higher in the sorafenib arm.

Topics: Administration, Oral; Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Capecitabine; Diarrhea; Disease-Free Survival; Double-Blind Method; Drug Administration Schedule; Drug Resistance, Neoplasm; Female; Hand-Foot Syndrome; Humans; Hypertension; Kaplan-Meier Estimate; Middle Aged; Niacinamide; Phenylurea Compounds; Placebos; Receptor, ErbB-2; Sorafenib; Taxoids; Treatment Outcome

The efficacy of lapatinib versus trastuzumab combined with taxanes in the first-line setting of human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (BC) is unknown.. The MA.31 trial compared a combination of first-line anti-HER2 therapy (lapatinib or trastuzumab) and taxane therapy for 24 weeks, followed by the same anti-HER2 monotherapy until progression. Stratification was by prior (neo)adjuvant anti-HER2 therapy, prior (neo)adjuvant taxane, planned taxane, and liver metastases. The primary end point was intention-to-treat (ITT) progression-free survival (PFS), defined as time from random assignment to progression by RECIST (version 1.0) criteria, or death for patients with locally assessed HER2-positive tumors. The primary test statistic was a stratified log-rank test for noninferiority. PFS was also assessed for patients with centrally confirmed HER2-positive tumors.. From July 17, 2008, to December 1, 2011, 652 patients were accrued from 21 countries, resulting in 537 patients with centrally confirmed HER2-positive tumors. Median follow-up was 21.5 months. Median ITT PFS was 9.0 months with lapatinib and 11.3 months with trastuzumab. By ITT analysis, PFS was inferior for lapatinib compared with trastuzumab, with a stratified hazard ratio (HR) of 1.37 (95% CI, 1.13 to 1.65; P = .001). In patients with centrally confirmed HER2-positive tumors, median PFS was 9.1 months with lapatinib and 13.6 months with trastuzumab (HR, 1.48; 95% CI, 1.20 to 1.83; P < .001). More grade 3 or 4 diarrhea and rash were observed with lapatinib (P < .001). PFS results were supported by the secondary end point of overall survival, with an ITT HR of 1.28 (95% CI, 0.95 to 1.72; P = .11); in patients with centrally confirmed HER2-positive tumors, the HR was 1.47 (95% CI, 1.03 to 2.09; P = .03).. As first-line therapy for HER2-positive metastatic BC, lapatinib combined with taxane was associated with shorter PFS and more toxicity compared with trastuzumab combined with taxane.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Bridged-Ring Compounds; Diarrhea; Disease-Free Survival; Drug Administration Schedule; Drug Eruptions; Female; Follow-Up Studies; Humans; International Cooperation; Kaplan-Meier Estimate; Lapatinib; Middle Aged; Neoplasm Staging; Patient Selection; Quality of Life; Quinazolines; Receptor, ErbB-2; Taxoids; Trastuzumab; Treatment Outcome

Lenalidomide, a highly potent immunomodulatory derivative of thalidomide, potentiates the action of paclitaxel in vitro against prostate cancer cell lines in co-culture with mononuclear cells. A modular Phase I study of lenalidomide and paclitaxel in men with metastatic castration-resistant prostate cancer (CRPC) was conducted to assess PSA kinetics with lead-in lenalidomide and the feasibility of the combination.. Men with metastatic CRPC with prior taxane chemotherapy were planned for single-agent "lead-in" lenalidomide for 21/28 days at dose-levels: -1 (5 mg), 0 (10 mg), +1 (15 mg), +2 (20 mg), +3 (25 mg); followed by lenalidomide at the same dose and schedule in combination with weekly intravenous paclitaxel 100 mg/m(2) over 3 h on days 1, 8, 15 every 28 days utilizing a 3 + 3 dose-escalation design.. Dose-limiting toxicity was observed in 4/6 patients with first-cycle combination therapy at the 10 mg dose-level and 3/6 patients at the 5 mg dose-level of lenalidomide, respectively. These included Grade 3 neutropenia precluding planned paclitaxel therapy (n = 3), grade 3 gastrointestinal toxicity (n = 2), chest pain (n = 1) and pulmonary embolism (n = 1). With lead-in lenalidomide, two patients with lymph-node dominant CRPC had a PSA-decline and regression in lymph node disease, respectively. Two of seven evaluable patients had PSA declines by 50% with combination therapy. Progression-free survival was 13 weeks (range 4-35 weeks).. The high dose-limiting toxicity rates observed with lenalidomide and weekly paclitaxel require exploration of alternate dose-schedules of the combination in the second-line setting of CRPC. These early observations suggest distinctive toxicity and efficacy outcomes from thalidomide in combination with paclitaxel.

Topics: Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Combined Modality Therapy; Diarrhea; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Lenalidomide; Male; Middle Aged; Nausea; Neutropenia; Orchiectomy; Paclitaxel; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Analysis; Taxoids; Thalidomide; Treatment Outcome; Vomiting

Treatment options are limited for patients with refractory metastatic breast cancer (MBC). Larotaxel (XRP9881) is a novel taxoid with preclinical activity against taxane-resistant breast cancer. The current phase II trial of larotaxel was conducted in women with taxane-treated MBC.. Patients were stratified by response to prior taxane therapy (resistant or nonresistant). Larotaxel 90 mg/m(2) was administered as a 1-h infusion every 3 weeks. Patients were evaluated for tumor response every two cycles. A blinded external response review committee determined the overall response rate (ORR), duration of response (DOR), and time to progression (TtP) of the disease. Median survival time (MST) and safety were also evaluated.. One hundred and thirty patients were treated. In the nonresistant group, the ORR was 42%; median DOR 5.3 months; median TtP 5.4 months; and MST 22.6 months. In the resistant group, the ORR was 19%; median DOR 5.0 months; median TtP 1.6 months; and MST 9.8 months. The most common grade 3/4 adverse events were neutropenia (82%), fatigue (15%), diarrhea (12%), febrile neutropenia (9%), neutropenic infection (8%), and sensory neuropathy (7%).. Larotaxel has good activity, manageable toxicity, and a favorable therapeutic index in women with taxane-pretreated MBC.

Topics: Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Cohort Studies; Diarrhea; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Fatigue; Female; Follow-Up Studies; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Middle Aged; Neoplasm Metastasis; Neutropenia; Prospective Studies; Taxoids; Time Factors; Treatment Outcome

Treatment options in patients with recurrent non-small cell lung cancer (NSCLC) remain limited as a result of poor activity of most agents after failure of platinum-based therapy. In the present phase I-II study, we evaluated the feasibility and efficacy of bi-weekly gemcitabine (GEM) + irinotecan (CPT-11) in patients with relapsed NSCLC.. Patients with advanced NSCLC, WHO-performance status (PS)

Topics: Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Blood Cell Count; Bridged-Ring Compounds; Camptothecin; Carcinoma, Non-Small-Cell Lung; Deoxycytidine; Diarrhea; Dose-Response Relationship, Drug; Female; Gemcitabine; Humans; Irinotecan; Lung Neoplasms; Male; Middle Aged; Neutropenia; Organoplatinum Compounds; Patient Compliance; Quality of Life; Survival Analysis; Taxoids

To determine the efficacy and safety of ZD6474, an orally available inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase with additional activity against the epidermal growth factor receptor (EGFR) tyrosine kinase, in patients with previously treated metastatic breast cancer.. Eligible patients had histologically confirmed metastatic breast cancer and had received prior treatment with an anthracycline and taxane; measurable disease was required. Patients were enrolled sequentially into one of two dose cohorts, 100 or 300 mg orally once daily; 28 days defined one cycle. The primary end point was objective response rate; pharmacokinetics and serial pharmacodynamic studies were obtained.. Forty-six patients were enrolled between May 2002 and April 2003, and 44 were evaluable for response. Diarrhea was the most commonly reported toxicity and seemed dose related (grade >/=2: 4.5% and 37.5% in the 100 and 300 mg cohorts, respectively). Rash was reported by 26% of patients but was never worse than grade 2. Seven patients in the 300 mg cohort had asymptomatic grade 1 prolongation of the QTc interval. Hypertension requiring treatment was not reported. There were no objective responses; one patient in the 300 mg cohort had stable disease >/=24 weeks. All patients in the 300 mg cohort and 90% of patients in the 100 mg cohort achieved steady-state concentrations exceeding the IC(50) for VEGF inhibition in preclinical models.. ZD6474 monotherapy was generally well tolerated but had limited monotherapy activity in patients with refractory metastatic breast cancer.

Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Breast Neoplasms; Bridged-Ring Compounds; Diarrhea; Dose-Response Relationship, Drug; ErbB Receptors; Female; Humans; Middle Aged; Nausea; Neoplasm Metastasis; Piperidines; Quinazolines; Taxoids; Treatment Outcome; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2

The APHINITY (BIG 4-11) study showed that pertuzumab significantly improved the rates of invasive disease-free survival among patients with human epidermal growth factor receptor 2 (HER2)-positive, operable breast cancer when added to adjuvant trastuzumab and chemotherapy. Because diarrhea was a common adverse event that could compromise treatment administration, we evaluated the incidence and management of diarrhea in the APHINITY study.. The APHINITY trial is a prospective, randomized, multicenter, multinational, double-blind, placebo-controlled trial. The eligible patients were randomly assigned to receive standard adjuvant chemotherapy and 1 year of trastuzumab combined with pertuzumab or placebo. The diarrhea incidence, severity (National Cancer Institute common terminology criteria for adverse events, version 4.0), onset, and management were analyzed.. A total of 4805 patients were randomized. Diarrhea of any grade was the most common adverse event and occurred in 71% of patients in the pertuzumab arm versus 45% in the placebo arm. Diarrhea grade 3 to 4 was observed in 10% and 4% in the pertuzumab and placebo arms, respectively. The greatest incidence of diarrhea was reported during the concomitant administration of HER2-targeted therapy and taxane (61% vs. 34% of patients experienced an event with pertuzumab vs. placebo, respectively). A marked decrease was observed on chemotherapy cessation. Antidiarrheal agents were commonly used, and diarrhea rarely caused treatment dose modifications or discontinuation.. Diarrhea was a common adverse event in the APHINITY study. Most episodes were low grade and were generally manageable with common antidiarrheal agents. The incidence of diarrhea was greater with the combination of a taxane and HER2-targeted treatment and decreased once chemotherapy was stopped.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antidiarrheals; Antineoplastic Combined Chemotherapy Protocols; Breast; Breast Neoplasms; Bridged-Ring Compounds; Chemotherapy, Adjuvant; Diarrhea; Disease-Free Survival; Female; Humans; Incidence; Mastectomy; Middle Aged; Multicenter Studies as Topic; Progression-Free Survival; Prospective Studies; Randomized Controlled Trials as Topic; Receptor, ErbB-2; Severity of Illness Index; Taxoids; Trastuzumab