The effect of tamoxifen or exemestane on bone mineral density during the first 2 years of adjuvant treatment of postmenopausal women with early breast cancer.

BACKGROUND: Adjuvant therapy with aromatase inhibitors is associated with increased bone loss in postmenopausal women with breast cancer. We assessed changes in bone mineral density (BMD) from baseline to 24 months in patients receiving either tamoxifen (T) or exemestane (E). PATIENTS AND METHODS: A total of 578 women randomly assigned to T 20 mg per day orally or E 25 mg/day orally enrolled in this substudy; baseline, 12-month, and 24-month BMD measurements of the femur and lumbar spine by dual-energy x-ray absorptiometry were planned. Women receiving bone antiresorptive agents were excluded. Mean BMD changes from baseline to 12 and 24 months were tested between the treatment groups using 2-sample t tests and both g/cm2 (as percent changes) and T scores (as differences from baseline). RESULTS: A total of 167 women with all 3 imaging studies were evaluable and form the basis of this report (T=89, E=78). Using T scores, the mean difference from baseline was significant between the 2 groups at 12 months at both the spine (P=.0002) and the hip (P=.0004), and at 24 months only at the hip (P=.02). CONCLUSION: More bone loss occurred during the first 12 months of treatment with E compared with T, but by 2 years the differences were less apparent and bone loss with E had slowed.

Phase II trial of capecitabine and weekly paclitaxel in patients with metastatic breast cancer previously treated with every-3-week taxane therapy.

PURPOSE: We conducted a multicenter phase II trial to determine the efficacy/safety of capecitabine and weekly paclitaxel, a combination with preclinical evidence of synergy, in patients with metastatic breast cancer (MBC) previously treated with a taxane. PATIENTS AND METHODS: Eligibility criteria included measurable MBC, history of every-3-week taxane therapy (adjuvant or for MBC), and no previous taxane on a weekly basis, capecitabine, or infusional 5-fluorouracil. Patients received capecitabine 825 mg/m2 per dose orally twice daily (1650 mg/m2 per day) on days 1-14 and weekly paclitaxel 80 mg/m2 intravenously on days 1 and 8, followed by a 1-week rest period (every-3-week cycle) until progression or intolerable toxicity. Fifty-four women were treated, most with previous every-3-week taxane exposure as adjuvant therapy (n=43) rather than for MBC (n=11). The median number of delivered cycles was 7, with dose modifications in 30 patients. The intent-to-treat objective response rate (primary study endpoint) was 59% (95% confidence interval, 46%-72%), including 7 complete and 25 partial responses. RESULTS: Three patients had stable disease for>or=6 months, for a clinical benefit rate of 65% (95% confidence interval, 51%-76%). Median objective response duration, time to progression, and overall survival were 8.1 months, 8.4 months, and 21.6 months, respectively. Grade 3/4 treatment-related adverse events consisted of neutropenia (13%), anemia (2%), hand-foot skin reaction (20%), fatigue (7%), diarrhea (4%), nausea/vomiting (4%), and pain (2%). No patients developed grade 3/4 neuropathy. CONCLUSION: Capecitabine and weekly paclitaxel were highly active with acceptable tolerability in patients with MBC previously treated with a taxane, consistent with our recently published experience in taxane-naive women with MBC.

Results of a Phase II study of weekly docetaxel and carboplatin in Stage IIIB (with effusion) or Stage IV non-small cell lung cancer patients age

This study explores if advanced NSCLC patients with ECOG PS 2 and age

Phase II trial of weekly docetaxel/ gemcitabine as first-line chemotherapy in patients with locally recurrent or metastatic breast cancer.

PURPOSE: A phase II study evaluated weekly docetaxel/gemcitabine as first-line chemotherapy for locally recurrent or metastatic breast cancer in a multicenter community oncology practice setting. PATIENTS AND METHODS: Eligible patients who had not received chemotherapy for metastatic disease received docetaxel 30 mg/m2 followed by gemcitabine 800 mg/m2, each administered weekly for 3 weeks (days 1, 8, and 15), followed by a 1-week rest period (28-day cycle). Patients also received oral dexamethasone to reduce the incidence/severity of fluid retention and hypersensitivity reactions. Of the 46 enrolled patients, 45 were treated as part of the intent-to-treat (ITT) population and were evaluable for safety. RESULTS: There were 3 complete responses and 12 partial responses among the 39 evaluable patients, for an objective response rate (ORR) of 39% (95% confidence interval [CI], 24%-54%). The ORR in the ITT population was 33% (95% CI, 18%-48%). Median time to response was 3.4 months, with a median response duration of 6.7 months. Median survival was 15.8 months, and median time to progression was 5.8 months. The most common grade 3/4 hematologic toxicity was neutropenia (13.3%); there was a low incidence of other grade 3/4 hematologic toxicities. Grade 3 fatigue (15.6%) was the most common grade 3/4 nonhematologic toxicity, and grade 2 alopecia occurred in 47% of patients. One patient who had been receiving chronic corticosteroid therapy died from treatment-related neutropenia and acute respiratory distress syndrome. CONCLUSION: These phase II results suggest that weekly docetaxel/gemcitabine is moderately active and well tolerated as first-line therapy for locally recurrent or metastatic breast cancer. No clear advantage for combined weekly docetaxel/gemcitabine was observed compared with published results on the efficacy of docetaxel and gemcitabine given as single agents.

A phase II study of weekly paclitaxel/estramustine/carboplatin in hormone-refractory prostate cancer.

PURPOSE: The objective of this phase II study was to determine the response rate in patients with hormone-refractory prostate cancer given paclitaxel/estramustine/carboplatin for weeks 1, 2, and 3 of a 4-week cycle. PATIENTS AND METHODS: Eighty-four patients were registered into the trial. Paclitaxel 80 mg/m2 and carboplatin area under the curve of 2 were administered intravenously on days 2, 9, and 16, and oral estramustine 280 mg 3 times daily was given on days 1-3, 8-10, and 15-17 for 6 cycles. Eastern Cooperative Oncology Group performance status 0, 1, and 2 was 46%, 41%, and 13%, respectively, and median age was 70 years (range, 53-82 years), with 58 patients (69%) aged > 65 years. The majority of patients (83%) were white. Fifteen patients (18%) had received previous chemotherapy, 61 patients (73%) had undergone previous surgery, and 51 patients (61%) had received previous external-beam radiation therapy. RESULTS: Intent-to-treat analysis revealed a > or = 50% prostate-specific antigen decrease rate of 61%. Median survival was 15.3 months. The most frequent grade > or = 3 toxicities included fatigue (11%), nausea (10%), neutropenia (9%), anemia (6%), and vomiting (6%). CONCLUSION: Paclitaxel/estramustine/carboplatin administered in a weekly regimen is highly effective in the treatment of hormone-refractory prostate cancer and can be administered with reasonable safety in an outpatient setting.

Phase II trial of docetaxel/capecitabine in hormone-refractory prostate cancer.

BACKGROUND: Docetaxel is the most active single agent in the treatment of hormone-refractory prostate cancer (HRPC). Because of the preclinical and clinical evidence of synergy of capecitabine and docetaxel, it was hypothesized that this combination would be active and tolerable in HRPC. PATIENTS AND METHODS: Patients received docetaxel 60 mg/m2 intravenously over 60 minutes on day 1 of each 21-day cycle and capecitabine 1000 mg/m2 administered orally twice daily on days 1-14 of each cycle for a maximum of 8 cycles or until disease progression or intolerable toxicity. Seventy-seven patients were enrolled at 43 US Oncology sites. The median age was 69.3 years (range, 48-86 years); 86% were white, and the Eastern Cooperative Oncology Group performance status scores of 0 and 1 were 49% and 51% respectively. Sixty-nine (90%) patients were evaluated for prostate-specific antigen response. RESULTS: Overall, 41% of patients had a decreased prostate specific antigen level > or = 50%. There were 4 complete responses (6%), 24 partial responses (35%), 29 incidences of stable disease (43%), and 11 incidences of progressive disease (16%). Nine patients has stable disease > or = 6 months and the clinical benefit rate was 54%. The median time to response was 1.5 months (range, 1-16.9 months). The estimated survival at 12 and 24 months (range, < 1-27 months). There were no treatment-related deaths. Grade 3/4 toxicities included neutropenia (50%), leukopenia (22%), hand-foot syndrome (17%), fatigue (11%), and nausea (11%). CONCLUSION: Docetaxel/capcitabine is an active and tolerable combination in HRPC. Toxicity was acceptable and anticipated. Response rate and survival are comparable with other docetaxel combinations.

Results of a phase II study of weekly paclitaxel plus carboplatin in patients with extensive small-cell lung cancer with Eastern Cooperative Oncology Group Performance Status of 2, or age > or = 70 years.

PURPOSE: To determine the 1-year survival, response rate (RR), time to progression (TTP), and safety of weekly paclitaxel plus carboplatin (PC) in patients with extensive small-cell lung cancer (ESCLC) with an Eastern Cooperative Performance Status performance status (PS) of 2 or an age > or = 70 years. PATIENTS AND METHODS: Patients were treated with PC (paclitaxel 80 mg/m(2) and carboplatin area under the curve = 2) by intravenous infusion on days 1, 8, and 15 of every 4-week cycle for up to six cycles. RESULTS: Between July 2000 and December 2001, 77 eligible patients (50.6% were male, 97.4% were white, 44.2% had PS of 2, with median age of 74 years) with ESCLC were enrolled. Among the 66 patients who were assessable for response, 25 responded to treatment (one complete response and 24 partial responses), for an objective RR of 38%. There were eight cases of stable disease (12.1%) and 33 cases of progressive disease (50%). The median survival was 7.2 months (range, < 1 to 24.4 months), and the estimated 1-year survival rate was 30%. The median TTP was 3.5 months (range, < 1 to 21.2 months), and the estimated 1-year progression-free survival rate was 8%. The median duration of response was 4.5 months (range, 1.6 to 17.5 months). One death (sepsis) was possibly related to the study drugs. Grades 3 and 4 toxicities experienced by > or = 5% of patients included neutropenia (22.1%), fatigue (8.6%), anemia (5.2%), and nausea/vomiting (5.2%). CONCLUSION: This regimen produced relatively few toxicities (only two of the 66 assessable patients received fewer than two cycles because of toxicity), and both the median and 1-year survival were similar to other regimens. This regimen may be a preferable treatment choice for patients with ESCLC who have a poor PS or who are aged > or = 70 years.

Results of a Phase II study of carboplatin plus gemcitabine in patients with untreated extensive small cell lung cancer.

PURPOSE: To determine the response rate (RR) and survival produced by carboplatin + gemcitabine therapy in patients with untreated extensive small cell lung cancer (ESCLC). PATIENTS AND METHODS: Treatment consisted of carboplatin (AUC = 5) on day 1 and gemcitabine (1100 mg/m(2)) on days 1 and 8 of each 21-day cycle for 4 planned cycles (additional cycles allowed as per treating physician). ECOG performance status 0/1/2 was 29, 58, and 13%. Median age was 66.5 years (range: 41.3-83.1), 94% were white, and 50.7% were female. RESULTS: Between August 2000 and February 2002, 69 patients with ESCLC were enrolled. All 69 patients were included in the safety analysis, and 66 patients were evaluable for response. There were 2 CR (3.0%), 26 PR (39.5%), 23 SD (34.8%), and 15 PD (22.7%) resulting in a RR of 42.5%. The median survival was 9.2 months (range: <1-22.6), and the estimated 1-year survival was 33%. The median TTP was 3.9 months (range: <1-12.8), and the estimated 6-month progression free survival was 24%. The median duration of response was 3.8 months (range: 1.0-9.9). Out of 69 patients, 29, 3, and 16 received 4, 5, and 6 cycles of therapy, respectively. The major Grade 3, 4 toxicities included neutropenia (39.1%), thrombocytopenia (31.9%), anemia (13.0%), and fatigue (4.3%). CONCLUSION: This regimen resulted in survival data that was similar to other regimens for ESCLC and treatment appeared to be well tolerated. Gemcitabine in combination with carboplatin or other active drugs in ESCLC may be worth further investigation.

A randomized phase III trial of combined paclitaxel, carboplatin, and radiation therapy followed by weekly paclitaxel or observation for patients with locally advanced inoperable non-small-cell lung cancer.

BACKGROUND: This study was designed to determine the efficacy and safety of additional maintenance chemotherapy after standard induction chemotherapy/radiation therapy (XRT) in stage III non-small-cell lung cancer (NSCLC). The primary objective was to increase 1-year survival. PATIENTS AND METHODS: Eligible patients (N = 220) had confirmed stage IIIA or IIIB NSCLC, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Patients received induction chemotherapy (paclitaxel 200 mg/m(2) + carboplatin AUC = 6/3 weeks) for 2 cycles, followed by paclitaxel 45 mg/m(2) + carboplatin AUC = 2 weekly ×7 and concurrent daily XRT (cumulative dose = 66.6 Gy in 37 fractions) and then observation or maintenance. Before randomization, 101 patients (46%) discontinued treatment due to progressive disease (n = 34), toxicity (n = 33), patient request (n = 13), death (n = 7), or other (n = 14). The remaining 119 patients were randomly assigned to either "observation" or "maintenance" (6 cycles of paclitaxel 70 mg/m(2)/wk [3 weeks on/1 week off]); a median of 5 of 6 planned cycles was delivered in the maintenance arm. RESULTS: For the observation group vs. the maintenance group, the estimated 1- and 4-year survival rates were 77% vs. 66% and 38% vs. 17% (median, 26.9 months vs. 16.1 months, respectively [P = .07]); the estimated 1- and 4-year performance-free survival (PFS) were 46% vs. 24% and 25% vs. 13% (median, 10.2 months vs. 8.2 months, respectively [P = .04]). Common toxicities were neutropenia, thrombocytopenia, and fatigue. CONCLUSION: Median survival in both groups surpassed the standard, most notably the 26.9-month survival in the observation group. Maintenance chemotherapy, when added to a regimen of both induction and concurrent chemoradiotherapy, did not improve clinical outcomes, with endpoints favoring the standard arm.

A phase II study of pemetrexed in patients with advanced hepatocellular carcinoma.

Pemetrexed has demonstrated activity in hepatocellular carcinoma (HCC) cell lines, and has a manageable toxicity profile in clinical trials, suggesting its potential as a treatment for HCC patients. A multicenter, Phase II community-based study was conducted to assess the response rate and toxicity profile of single-agent pemetrexed in first-line patients with advanced or metastatic HCC. Patients premedicated with folic acid, vitamin B(12), and dexamethasone were administered pemetrexed 600 mg/m(2) IV on day 1 of each 21-day cycle until disease progression. This nonrandomized study employed Simon's 2-stage design, enrolling 21 eligible patients in the first stage, stopping accrual if < or =2 responders were observed. Responses were four stable disease, 14 progressive disease, and three not evaluable: two had early toxicities (renal/liver failure, sepsis) and one was noncompliant. The most common grade 3 hematological toxicities were neutropenia 6 of 21 (29%) and thrombocytopenia 3 of 21 (14%); with no grade 4 toxicities. Thirteen patients died on-study: 12 PD and one liver failure; none were drug-related. The median survival was 5.2 months (range, <1-12.2). The planned second stage was cancelled, and the trial was closed owing to lack of response. While pemetrexed was tolerated in this patient population, it was not active.

Favorable survival observed after carboplatin, paclitaxel, and concurrent accelerated hyperfractionated radiotherapy for treatment of locally advanced head and neck carcinoma.

PURPOSE: Several trials have demonstrated the superiority of simultaneous chemoradiotherapy compared with radiation alone for patients with locally advanced head and neck cancers. However, the optimal regimen remains to be defined. This study assessed the safety and activity of combined carboplatin (C), paclitaxel (P), and twice-daily radiotherapy (RT) in a community based, multicenter, phase II trial. MATERIALS AND METHODS: Eligible patients (N = 52) had ECOG PS 0-2 and previously untreated, stage III or IV (M0), unresectable, squamous cell cancers of the head and neck. Treatment consisted of 6 weekly courses of C (AUC = 1), P (40 mg/m(2)/1-h) and twice-daily radiation (120 cGy BID; total dose of 6,960 cGy). Subsequently, patients with N2/N3 disease were permitted neck dissection. RESULTS: Median follow-up was 61 months. Sixty-seven percent (67%) of patients had stage IV (M0) disease at baseline. Fifty-five percent (55%) of treated patients experienced NCI Grade 3-4 dysphagia, stomatitis, or mucositis; 80% had > or = Grade 3 toxicity of any organ system. Median weight loss was 7.1 lbs; 35% of patients experienced 10% or more weight loss. Of 43 patients evaluable for response, responses were: 29 CR (67%), 7 PR (16%), 1 MR (2%), 4 SD (9%), and 2 PD (5%); the overall response rate (CR+PR) was 84%. For the entire cohort of 52 patients, the estimated overall survival at 36 months was 60%; progression-free survival was 50%. CONCLUSIONS: We conclude that weekly C + P and concurrent twice-daily hyperfractionated radiotherapy is tolerated and highly active in patients with unresectable, locally advanced squamous cell carcinoma of the head and neck.

Phase I study of a 3-drug regimen of gemcitabine/cisplatin/pemetrexed in patients with metastatic transitional cell carcinoma of the urothelium.

OBJECTIVES: Gemcitabine (G) plus cisplatin (C) is standard care for metastatic transitional cell carcinoma (TCC) of the urothelium. Pemetrexed (P), alone or in combination with G, is active in metastatic TCC. However, the safety and efficacy of P combined with GC therapy is unknown. This phase I trial was designed to determine the maximum tolerated dose (MTD) of GC followed by P+G in patients with metastatic TCC. METHODS: Cohorts of 3 to 6 patients received escalating doses 28-day cycles (maximum 6 cycles): G 800-1,000 mg/m2 on days 1 and 15; P 400-500 mg/m2 on day 15; and C 50-70 mg/m2 on day 1. All patients received folic acid, vitamin B12, and full supportive care. The 3+3 standard phase I escalation rule was used to determine MTD. RESULTS: Fifteen patients registered: 13/15 white males; median age 70 years (range, 53-82); 11/15 had KPS>or=90. At dose level 0, 2/4 patients experienced unrelated DLTs, and 1 patient was replaced (completed<1 cycle). Dose escalation proceeded to dose level 1. At level 1, 4/6 patients experienced DLTs; dosing decreased to level 0 and 4/5 patients experienced DLTs. The MTD was not determined. The 2 patients that completed 6 cycles both had partial responses. Grades 3-4 hematologic toxicities included neutropenia (60%), leukopenia (20%), and febrile neutropenia (13%). CONCLUSION: Adding P to the standard GC regimen as first-line therapy for metastatic TCC produced no benefit. The MTD exceeded therapeutic gemcitabine and cisplatin doses for urothelial cancer and thus the study was aborted.

Comparison of menopausal symptoms during the first year of adjuvant therapy with either exemestane or tamoxifen in early breast cancer: report of a Tamoxifen Exemestane Adjuvant Multicenter trial substudy.

PURPOSE: Hormonal breast cancer treatment increases menopausal symptoms in women. This study investigated differences between the symptoms associated with either adjuvant tamoxifen or exemestane. PATIENTS AND METHODS: Ten common symptoms were assessed by self-report questionnaire administered to 1,614 consecutive patients at baseline and every 3 months during the first year of a double-blind, randomized trial of postmenopausal women with early hormone receptor-positive breast cancer. Symptoms were categorized as none, mild, moderate, or severe. A hot flash score was calculated at each time point. Symptoms were analyzed by repeated-measures analysis of variance. Each time period was tested repeatedly against the baseline; an overall P value was assigned for each reported symptom. RESULTS: Compliance was excellent, with 7,286 questionnaires analyzed. Baseline symptom prevalence ranged from 2% (vaginal bleeding) to 60% to 70% (bone/muscle aches and low energy). There were no significant differences in vaginal bleeding, mood alteration, or low energy. Patients receiving tamoxifen had significantly more vaginal discharge (P < .0001). Exemestane patients reported more bone/muscle aches (P < .0001), vaginal dryness (P = .0004), and difficulty sleeping (P = .03). In both groups, the hot flash score peaked at 3 months and decreased thereafter. At 12 months, patients receiving tamoxifen had a significantly higher mean hot flash score (P = .03), with daily hot flashes increasing from baseline by 33% compared with a 7% increase from baseline with exemestane. CONCLUSION: At 12 months, exemestane was associated with fewer hot flashes and less vaginal discharge than tamoxifen, but with more vaginal dryness, bone/muscle aches, and difficulty sleeping. Symptoms were common in both groups.

Phase II Trial of a Novel Paclitaxel Schedule As Single-Agent, First-Line Therapy for HER-2/neu-Negative Metastatic Breast Cancer: A Community-Based Study.

PURPOSE: To determine the response rate (RR), progression-free survival (PFS), and toxicity in patients with HER-2/neu-negative metastatic breast cancer treated with first-line paclitaxel in a de-escalating dosing schedule. PATIENTS AND METHODS: Between August 1999 and December 2000, 73 patients were enrolled. Paclitaxel was administered on day 1 (175 mg/m(2)) and on days 8 and 15 (80 mg/m(2) each) in each 4-week cycle (1 week of rest). Doses were de-escalated with the aim of reducing toxicity. An Eastern Cooperative Oncology Group performance status of 0, 1, or 2 was found in 55%, 41%, and 4% of patients, respectively. Median age was 59 years (range, 38 to 84 years), and 86% of patients had received prior surgery; 60%, adjuvant chemotherapy; and 59%, radiation therapy. RESULTS: Based on an intention-to-treat analysis (N = 73), there were five patients with a complete response (6.8%), 16 with a partial response (21.9%), 17 with stable disease (23.3%), and 23 with progressive disease (31.5%) for an RR of 28.7%. Twelve patients (16.4%) were not assessable for response due to toxicity (seven patients, mainly neuropathy), withdrawal of consent (two patients), early death (two patients), or noncompliance (one patient). Median PFS was 6.5 months (range, < 1 to 36.1 months), median survival was 22.8 months (range, < 1 to 36.1 months), and median duration of response was 8.8 months (range, 3.0 to 31.8 months). Patients (n = 72) were evaluated for toxicity. Grade 3 to 4 treatment-related toxicities occurring in more than 5% of patients included neutropenia (22.2%), neuropathy (18.1%), fatigue (6.9%), and leukopenia (5.6%). CONCLUSION: In a unique de-escalating schedule, this study of single-agent paclitaxel produced a response rate similar to other single-agent paclitaxel schedules, in first-line therapy for metastatic breast cancer, published in the literature. However, this schedule is not recommended for the therapy of metastatic breast cancer because of the higher rate of toxicity.

Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer.

PURPOSE: This randomized, multicenter, phase III trial evaluated the efficacy and safety of trastuzumab and paclitaxel with or without carboplatin as first-line therapy for women with HER-2-overexpressing metastatic breast cancer (MBC). PATIENTS AND METHODS: HER-2 overexpression was defined as immunohistochemical staining scores of 2+ or 3+. Between November 1998 and May 2002, 196 women with HER-2-overexpressing MBC were randomly assigned to six cycles of either trastuzumab 4 mg/kg loading dose plus 2 mg/kg weekly thereafter with paclitaxel 175 mg/m2 every 3 weeks (TP), or trastuzumab 4 mg/kg loading dose plus 2 mg/kg weekly thereafter with paclitaxel 175 mg/m2 and carboplatin area under the time-concentration curve = 6 every 3 weeks (TPC) followed by weekly trastuzumab alone. RESULTS: Baseline characteristics of the 196 patients were well balanced between study arms. Objective response rate (ORR) was 52% (95% CI, 42% to 62%) for TPC versus 36% (95% CI, 26% to 46%) for TP (P = .04). Median progression-free survival (PFS) was 10.7 months for TPC and 7.1 months for TP (hazard ratio [HR], 0.66; 95% CI, 0.59 to 0.73; P = .03). Improved clinical outcomes with TPC were most evident in HER-2 3+ patients, with an ORR of 57% (95% CI, 45% to 70%) v 36% (95% CI, 25% to 48%; P = .03) and median PFS of 13.8 v 7.6 months (P = .005) for TPC and TP, respectively (HR, 0.55; 95% CI, 0.46 to 0.64). Both regimens were well tolerated, and febrile neutropenia and neurotoxicity occurred infrequently; grade 4 neutropenia occurred more frequently with TPC (P < .01). CONCLUSION: The addition of carboplatin to paclitaxel and trastuzumab improved ORR and PFS in women with HER-2-overexpressing MBC. This well-tolerated regimen represents a new therapeutic option.

Phase II trial of capecitabine and weekly paclitaxel as first-line therapy for metastatic breast cancer.

PURPOSE: The taxanes and capecitabine have synergistic antitumor activity in preclinical models. This trial was designed to determine the efficacy and tolerability of weekly paclitaxel plus capecitabine as first-line treatment for metastatic breast cancer (MBC). PATIENTS AND METHODS: Participants had histologically proven breast cancer, with measurable metastatic disease by Response Evaluation Criteria in Solid Tumors Group. Exclusion criteria included prior taxane therapy or any prior capecitabine or infusional fluorouracil. Participants received capecitabine 825 mg/m2/dose orally bid (1,650 mg/m2/d) for days 1 to 14. Paclitaxel 80 mg/m2 was administered intravenously weekly on days 1 and 8. Cycles were repeated every 3 weeks. Responders (complete or partial) or those with stable disease were treated until progression of disease or intolerable toxicity. RESULTS: Fifty-five women were enrolled; 94% received study therapy as first-line treatment for MBC. In the intent-to-treat population, objective responses (partial) were achieved in 30 patients (55%; 95% CI, 40% to 69%), and six additional patients had stable disease for 6 months or longer (clinical benefit rate of 65%). The median duration of response was 10 months (range, 2.5 to 18.7 months). Dose modifications and reductions were common, particularly for capecitabine, leading to a delivered dose-intensity of 75% for capecitabine and 91% for paclitaxel. The most frequent grade 3 to 4 treatment-related adverse events were hand-foot skin reaction (n = 10); neutropenia (n = 7); fatigue (n = 4); and leukopenia, diarrhea, and pain (n = 3 each). CONCLUSION: Capecitabine in combination with weekly paclitaxel is an active and tolerable regimen as first-line therapy for women with MBC.