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Robert W Carlson

Publications and source records attributed to Robert W Carlson.

At least 19 recordsLinked to original sources
PubMed2006

Breast cancer followed by corpus cancer: is there a higher risk for aggressive histologic subtypes?

OBJECTIVE: To analyze corpus cancer patients with a breast cancer history for risk of developing aggressive uterine histologic types. METHODS: Corpus cancer patients with a history of breast cancer were identified from the Surveillance Epidemiology and End Results database from 1988 to 2001. Demographics, clinico-pathologic, and survival data were analyzed using Kaplan-Meier and logistic regression analyses. RESULTS: Of 52,109 women diagnosed with corpus cancer, 1922 had a history of breast cancer. Women with a history of breast cancer had a significantly higher proportion of uterine papillary serous carcinomas (UPSC) and sarcomas compared to those without a breast cancer history (9.4% vs. 6.3% for UPSC and 10.3% vs. 8.4% for sarcoma; P < 0.001). Patients with endometrioid or sarcoma of the uterus after breast cancer had significantly worse 5-year survivals than patients without a breast cancer history (84.4% vs. 90.5%; P < 0.001 and 49.0% vs. 63.6%, P < 0.001, respectively). Older age, advanced stage, lack of surgery and radiation treatment, poor histologic types, and history of breast cancer were independent prognostic factors for poorer survival. CONCLUSION: In this study, the proportional incidence of UPSC and sarcoma was significantly higher in women with a breast cancer history. These findings highlight the association of breast cancer and high-risk corpus cancer subtypes.

Adult↗
PubMed2006

A pilot phase II trial of valspodar modulation of multidrug resistance to paclitaxel in the treatment of metastatic carcinoma of the breast (E1195): a trial of the Eastern Cooperative Oncology Group.

BACKGROUND: To assess the activity and toxicity of valspodar (PSC-833) in combination with paclitaxel in women with anthracycline refractory, metastatic breast cancer. PATIENTS AND METHODS: Limited, multi-institutional, Phase II trial of valspodar at 5 mg/kg/dose orally every 6 hours for 12 doses in combination with paclitaxel 70 mg/m2 administered intravenously as a 3-hour infusion beginning 4 hours after the fifth dose of valspodar, every 3 weeks. Eligible patients had bi-dimensionally measurable metastatic carcinoma of the breast, prior anthracycline therapy or a medical contraindication to anthracycline therapy, no more than one prior chemotherapy for recurrent or metastatic breast cancer, and adequate organ function. Treatment was continued until disease progression or unacceptable toxicity. RESULTS: Thirty-four patients are evaluable for response and 37 for toxicity. Two (6 percent) patients achieved a complete response and 5 (15 percent) a partial response for an objective response rate of 21 percent (95 percent confidence interval of 9 to 38 percent). Median duration of response was 9.7 months (95 percent confidence interval 8.0-17.2 months), median time to progression was 3.3 months (95 percent confidence interval 2.0-4.2 months), and median survival was 12 months (95 percent confidence interval 8.1-17.3 months). The toxicity experienced was acceptable. CONCLUSIONS: Combination valspodar plus paclitaxel is an active regimen and has acceptable toxicity. The combination is not clearly more active than single agent paclitaxel.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Clathrate hydrates of oxidants in the ice shell of Europa.

Europa's icy surface is radiolytically modified by high-energy electrons and ions, and photolytically modified by solar ultraviolet photons. Observations from the Galileo Near Infrared Mapping Spectrometer, ground-based telescopes, the International Ultraviolet Explorer, and the Hubble Space Telescope, along with laboratory experiment results, indicate that the production of oxidants, such as H2O2, O2, CO2, and SO2, is a consequence of the surface radiolytic chemistry. Once created, some of the products may be entrained deeper into the ice shell through impact gardening or other resurfacing processes. The temperature and pressure environments of regions within the europan hydrosphere are expected to permit the formation of mixed clathrate compounds. The formation of carbon dioxide and sulfur dioxide clathrates has been examined in some detail. Here we add to this analysis by considering oxidants produced radiolytically on the surface of Europa. Our results indicate that the bulk ice shell could have a approximately 1.7-7.6% by number contamination of oxidants resulting from radiolysis at the surface. Oxidant-hosting clathrates would consequently make up approximately 12-53% of the ice shell by number relative to ice, if oxidants were entrained throughout. We examine, in brief, the consequences of such contamination on bulk ice shell thickness and find that clathrate formation could lead to substantially thinner ice shells on Europa than otherwise expected. Finally, we propose that double occupancy of clathrate cages by O2 molecules could serve as an explanation for the observation of condensed-phase O2 on Europa. Clathrate-sealed, gas-filled bubbles in the near surface ice could also provide an effective trapping mechanism, though they cannot explain the 5771 A (O2)2 absorption.

Ice↗
PubMed2006

Adjuvant endocrine therapy in hormone receptor-positive postmenopausal breast cancer: evolution of NCCN, ASCO, and St Gallen recommendations.

Endocrine therapy has a firm role in adjuvant treatment of women with hormone receptor-positive invasive breast cancer. Until recently, tamoxifen was the most commonly used adjuvant endocrine therapy in premenopausal and postmenopausal women. Several randomized clinical trials have studied the third-generation selective aromatase inhibitors (AIs) (anastrozole, letrozole, and exemestane) as adjuvant endocrine therapy in postmenopausal women. These studies compared therapy with an AI alone versus tamoxifen alone; 2 to 3 years of tamoxifen followed by switching to an AI versus continuation of tamoxifen; or extended therapy with an AI after approximately 5 years of tamoxifen therapy. No statistically significant differences in overall survival were observed. A single trial using extended treatment with an adjuvant AI suggests a small, statistically significant survival advantage in women with axillary lymph node-positive disease while showing no statistically significant decrease in survival with the use of an AI. The toxicities of the AIs are generally acceptable, with fewer endometrial cancers, gynecologic complaints, and thromboembolic events, but more bone fractures and arthralgias compared with tamoxifen alone. Three widely disseminated treatment guidelines, the National Comprehensive Cancer Network Breast Cancer Clinical Practice Guidelines in Oncology, the American Society of Clinical Oncology Technology Assessment on the Use of Aromatase Inhibitors, and the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer, now incorporate AIs in the adjuvant therapy of postmenopausal women with estrogen receptor-positive breast cancer.

Female↗
PubMed2006

NCCN Task Force Report: Adjuvant Therapy for Breast Cancer.

The National Comprehensive Cancer Network (NCCN) first published the NCCN Breast Cancer Treatment Guidelines in 1996. The Guidelines address the treatment of all stages of breast cancer across the spectrum of patient care and have been updated yearly. Adjuvant therapy for breast cancer has undergone an especially rapid evolution over the past few years. Therefore, the NCCN Breast Cancer Guidelines Panel was supplemented by additional experts to form the Adjuvant Therapy Task Force to provide a forum for an extended discussion and expanded input to the adjuvant therapy recommendations for the Breast Cancer Treatment Guidelines. Issues discussed included methods of risk-stratification for recurrence; how biologic markers such as HER2 status, quantitative estrogen receptor, or genetic markers can be incorporated as prognostic or predictive factors; and how age, menopausal status, and estrogen receptor levels impact benefits from chemotherapy and endocrine therapy. Additionally, the task force discussed the strategies for use of aromatase inhibitors in postmenopausal women and the potential incorporation of trastuzumab into adjuvant therapy of women with HER2/neu positive breast cancer. This supplement summarizes the background data and ensuing discussion from the Adjuvant Task Force meeting.

Adult↗
PubMed2006

HER2 testing in breast cancer: NCCN Task Force report and recommendations.

The NCCN HER2 Testing in Breast Cancer Task Force was convened to critically evaluate the ability of the level of HER2 expression or gene amplification in breast cancer tumors to serve as a prognostic and a predictive factor in the metastatic and adjuvant settings, to assess the reliability of the methods of measuring HER2 expression or gene amplification in the laboratory, and to make recommendations regarding the interpretation of test results. The Task Force is a multidisciplinary panel of 24 experts in breast cancer representing the disciplines of medical oncology, pathology, radiation oncology, surgical oncology, epidemiology, and patient advocacy. Invited members included members of the NCCN Breast Cancer Panel and other needed experts selected solely by the NCCN. During a 2-day meeting, individual task force members provided didactic presentations critically evaluating important aspects of HER2 biology and epidemiology: HER2 as a prognostic and predictive factor; results from clinical trials in which trastuzumab was used as a targeted therapy against HER2 in the adjuvant and metastatic settings; the available testing methodologies for HER2, including sensitivity, specificity, and ability to provide prognostic and predictive information; and the principles on which HER2 testing should be based. Each task force member was charged with identifying evidence relevant to their specific expertise and presentation. Following the presentations, an evidence-based consensus approach was used to formulate recommendations relating to the pathologic and clinical application of the evidence to breast cancer patient evaluation and care. In areas of controversy, this process extended beyond the meeting to achieve consensus. The Task Force concluded that accurate assignment of the HER2 status of invasive breast cancer is essential to clinical decision making in the treatment of breast cancer in both adjuvant and metastatic settings. Formal validation and concordance testing should be performed and reported by laboratories performing HER2 testing for clinical purposes. If appropriate quality control/assurance procedures are in place, either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) methods may be used. A tumor with an IHC score of 0 or 1+, an average HER2 gene/chromosome 17 ratio of less than 1.8, or an average number of HER2 gene copies/cell of 4 or less as determined by FISH is considered to be HER2 negative. A tumor with an IHC score of 3+, an average HER2 gene/chromosome 17 ratio of greater than 2.2 by FISH, or an average number of HER2 gene copies/cell of 6 or greater is considered HER2 positive. A tumor with an IHC score of 2+ should be further tested using FISH, with HER2 status determined by the FISH result. Tumor samples with an average HER2 gene/chromosome ratio of 1.8 to 2.2 or average number of HER2 gene copies/cell in the range of greater than 4 to less than 6 are considered to be borderline, and strategies to assign the HER2 status of such samples are proposed.

Advisory Committees↗
PubMed2005

Predictors of local recurrence after breast-conservation therapy.

Breast-conserving therapy (BCT) is a proven local treatment option for select patients with early-stage breast cancer. This paper reviews pathologic, clinical, and treatment-related features that have been identified as known or potential predictors for ipsilateral breast tumor recurrence in patients treated with BCT. Pathologic risk factors such as the final pathologic margin status of the excised specimen after BCT, the extent of margin involvement, the interaction of margin status with other adverse features, the role of biomarkers, and the presence of an extensive intraductal component or lobular carcinoma in situ all impact the likelihood of ipsilateral breast tumor recurrence. Predictors of positive repeat excision findings after conservative surgery include young age, presence of an extensive intraductal component, and close or positive margins in prior excision. Finally, treatment-related factors predicting ipsilateral breast tumor recurrence include extent of breast radiation therapy, use of a boost to the lumpectomy cavity, use of tamoxifen or chemotherapeutic agents, and timing of systemic therapy with irradiation. The ability to predict for an increased risk of ipsilateral breast tumor recurrence enhances the ability to select optimal local treatment strategies for women considering BCT.

Antineoplastic Agents, Hormonal↗
PubMed2005

Final results of a phase II trial of preoperative TAC (docetaxel/doxorubicin/cyclophosphamide) in stage III breast cancer.

BACKGROUND: The use of preoperative chemotherapy for breast cancer has been demonstrated to result in similar disease-free survival (DFS) and overall survival (OS) as postoperative adjuvant chemotherapy. Additionally, the rate of pathologic complete response (pCR) in the breast after preoperative chemotherapy has been shown to correlate with survival. The objective of this study was to determine the pCR rate in patients with stage III breast cancer treated with 4 cycles of TAC (docetaxel 75 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2) on day 1 before surgery. PATIENTS AND METHODS: From November 1998 through August 2001, we treated 40 patients (mean age, 47 years) with stage III breast cancer with TAC administered every 3 weeks for 4 cycles. RESULTS: We now report follow-up at 24 months. Responses were seen in 83% of patients, with 25% experiencing a clinical complete response, of which 4 patients (10%) had pCRs. At a follow-up of 2 years, data on DFS and OS are available on 37 patients: 12 patients (38%) had disease progression, and 7 patients (21%) had died. Despite the use of prophylactic ciprofloxacin, some degree of myelosuppression was seen in all patients, with 24 patients (63%) experiencing grade 3/4 neutropenia. CONCLUSION: Based on the pCR rate seen in this trial, docetaxel given concomitantly with AC (doxorubicin/cyclophosphamide) for 4 cycles does not appear to be superior to 4 cycles of AC as preoperative treatment for stage III breast cancer. Based on other trials, longer durations of therapy and/or sequencing of AC and docetaxel may result in a higher pCR rate.

Adult↗
PubMed2005

The history and mechanism of action of fulvestrant.

Fulvestrant is a pure antiestrogen that emerged from a systematic medicinal chemistry strategy of modification of long-chain alkyl substitutes in the 7a-position of estradiol. Fulvestrant has no uterotrophic effects on the immature or ovariectomized rat and blocks the agonistic effects of estradiol and tamoxifen in a dose-dependent manner. In in vivo and in vitro breast cancer models, fulvestrant has anticancer activity at least as good as tamoxifen and is superior to tamoxifen in some models. Fulvestrant requires intramuscular administration in a proprietary formulation of castor oil and alcohols. When fulvestrant binds to estrogen receptor monomers it inhibits receptor dimerization, activating function 1 (AF1) and AF2 are rendered inactive, translocation of receptor to the nucleus is reduced, and degradation of the estrogen receptor is accelerated. This results in pure antiestrogenic effects. There is substantial preclinical evidence that the nonsteroidal hormone-dependent mechanisms of estrogen receptor activation and regulation via growth factor receptors and their signal transduction pathways are important in the development of breast cancer hormonal resistance. Methods of exploiting the interactions between these nonsteroidal hormone-dependent mechanisms of resistance and hormonal agents such as fulvestrant are an active area for drug development and clinical investigation.

Animals↗
PubMed2005

Breast cancer.

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Antineoplastic Agents↗
PubMed2004

Rational surveillance programs for early stage breast cancer patients after primary treatment.

The majority of women with early stage breast cancers are successfully treated with surgery, radiation therapy and adjuvant systemic therapy. However, 30% of all Stage I and Stage II patients can be expected to experience a relapse. The belief that early detection of recurrences can lead to an increase in survival has been used to justify intensive follow-up regimens following primary treatment of patients with early stage disease. However, the vast majority of data support a program of scheduled surveillance visits and demonstrate that a comprehensive history and physical examination is as efficacious as programs utilizing intensive testing and imaging procedures in the asymptomatic patient. Screening mammography to detect ipsilateral in-breast recurrence or a new primary cancer in the contralateral breast is the only imaging study that is recommended for routine surveillance. Knowledge of the natural history of breast cancer, risk factors for relapse, and the symptoms and physical findings commonly associated with recurrence are central to efficiently and effectively monitoring this cohort of women in clinical practice.

Breast Neoplasms↗
PubMed2004

Adjuvant aromatase inhibitors following tamoxifen for early-stage breast cancer in postmenopausal women: what do we really know?

Adjuvant hormonal therapy in the treatment of women with early-stage, hormone receptor (HR)-positive breast cancer is now considered the standard of care. Adjuvant tamoxifen decreases the risk of breast cancer recurrence and death in women with early-stage breast cancer when taken for 5 years. The benefits of tamoxifen are counterbalanced by toxicities including an increased risk of endometrial cancer and thromboembolic events. The selective aromatase inhibitors (AIs)--including anastrozole, letrozole, and exemestane--are challenging the role of tamoxifen as the adjuvant hormonal therapy of choice in postmenopausal women. Results of the Arimidex and Tamoxifen Alone or in Combination trial favor the use of anastrozole over tamoxifen as initial adjuvant hormonal therapy, with improvement in disease-free survival (DFS) and a favorable toxicity profile. The results of 2 large adjuvant trials using AIs sequentially with tamoxifen in postmenopausal women with early-stage, HR-positive breast cancer have been reported. The MA-17 study randomized women to placebo or letrozole for 5 years after completion of 4.5-6 years of initial tamoxifen. The Intergroup Exemestane Study (IES) randomized women following 2-3 years of adjuvant tamoxifen to continue to receive tamoxifen or switch to exemestane for a total of 5 years of adjuvant hormonal therapy. The MA-17 and IES trials demonstrated superior DFS with the AI and corroborated the smaller GROCTA-4B and Italian Tamoxifen Arimidex trials, which studied sequential therapy with aminoglutethamide or anastrozole. There is now substantial medical evidence supporting the use of AIs in postmenopausal women with early-stage, HR-positive breast cancer.

Aged↗
PubMed2003

Predictors of reexcision findings and recurrence after breast conservation.

PURPOSE: To identify predictors of reexcision findings and local recurrence in the setting of breast-conserving therapy with radiation. METHODS: The records of 535 patients who underwent breast-conserving surgery followed by radiation for Stage I or II cancer between 1972 and 1996 were reviewed. The mean follow-up period for surviving patients without evidence of recurrence is 6 years. Various clinical and pathologic prognostic factors were examined for significance with regard to reexcision findings and recurrence rates. Pathologic margin status was classified as negative, close (<or=2 mm), positive, or indeterminate. RESULTS: The pathologic margin status was the most important predictor of local recurrence. The freedom from local relapse (FFLR) at 6 years was 97% for patients with negative pathologic margins and 86% for all others (p < 0.0001). There was no significant difference in recurrence rates among patients with close, positive, or indeterminate margins. However, the use and sequencing of systemic therapy affected recurrence rates among these patients. For patients with close, positive, or indeterminate margins, the crude risk of local recurrence was 4% among patients who received tamoxifen or received chemotherapy integrated with or after radiation. The risk of local recurrence was 16-29% among the patients with close, positive, or indeterminate margins who did not receive systemic therapy or who received radiation after completion of chemotherapy. Local recurrence rates were low in patients with negative margins (2-8%) regardless of the use of systemic therapy or its timing. The presence or absence of residual disease at reexcision did not predict recurrence as long as the final margins were negative. Among patients who underwent reexcision before radiation, extensive intraductal component (EIC) (p = 0.0001) and young patient age (p = 0.03) were predictive of residual disease in the specimen. Patients with initially close margins and no EIC had a low risk of residual disease at the time of reexcision, as did patients older than age 65 without EIC. CONCLUSION: Pathologic margin status is the most important predictor of local recurrence after breast conservation with radiation. Patient age and EIC were significant predictors of residual disease at reexcision. The use and timing of systemic therapy appear to influence the risk of local recurrence in patients who do not have negative lumpectomy margins.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

The role of aromatase inhibitors in early breast cancer.

The role of hormonal therapy for the treatment of patients with early stage breast cancer has been evaluated in many studies. The results of these studies establish tamoxifen as the gold standard of hormonal therapy for the adjuvant treatment of hormone receptor-positive invasive breast cancer in pre- and postmenopausal women. Studies show tamoxifen reduces the risk of invasive breast cancer in women at increased risk for the disease, including women with ductal carcinoma in situ. Tamoxifen has adverse effects such as hot flashes, increased risk of uterine cancer in postmenopausal women, and rare occurrence of thromboembolic disease. Despite the multiple therapeutic roles of tamoxifen, alternatives are needed. Aromatase inhibitors (AI) are drugs with antiestrogenic activity. AIs function by inhibiting the peripheral conversion of adrenally synthesized androstenedione to estradiol through inhibition of the aromatase enzyme. AIs do not suppress estradiol synthesis by the ovary adequately. Therefore, AIs are effective in reducing circulating estradiol levels in postmenopausal women, but not premenopausal women. Selective nonsteroidal AIs, including anastrozole (Arimidex; AstraZeneca, Wilmington, DE) and letrozole (Femara; Novartis, East Hanover, NJ), and the steroidal AI exemestane (Aromasin; Pharmacia, Peapack, NJ) have been associated with increased specificity and improved therapeutic index compared to nonselective AIs such as aminoglutethamide. Nonsteroidal and steroidal AIs have demonstrated to be superior to megestrol acetate in second-line therapy of postmenopausal women with metastatic breast cancer, and selective nonsteroidal AIs have shown to be superior to tamoxifen in first-line therapy of postmenopausal women with metastatic breast cancer. The ATAC (Arimidex, tamoxifen, alone, or in combination) trial is the only published randomized trial comparing the efficacy of an AI to tamoxifen for the adjuvant treatment of women with early breast cancer. This large study showed that at a median follow-up time of 33 months, anastrozole alone results in significant improvement in disease-free survival rates, reduction in contralateral breast cancers, and increased tolerability, compared to tamoxifen in postmenopausal women. Although the long-term effects of AIs are not known, the early positive results of the ATAC trial led to the approval of anastrozole by the US Food and Drug Administration for use as adjuvant hormonal therapy for postmenopausal women with hormone receptor-positive invasive breast cancer. Thus, there is an alternative to tamoxifen for postmenopausal women with relative/absolute contraindications to tamoxifen use or patients who choose not to take tamoxifen because of its side-effect profile. New AIs may challenge the position of tamoxifen as the gold standard for the treatment of early stage breast cancer in postmenopausal women.

Adult↗
PubMed2003

Sequential hormonal therapy for metastatic breast cancer after adjuvant tamoxifen or anastrozole.

The use of adjuvant endocrine therapy in the treatment of hormone receptor-positive, early breast cancer has become important in both pre- and postmenopausal women. Tamoxifen has been the principal adjuvant hormonal therapy in pre- and postmenopausal women with hormone receptor-positive breast cancer for nearly 20 years. Recent data in premenopausal women suggest benefit from ovarian ablation with or without tamoxifen. Early results from the 'Arimidex', Tamoxifen, Alone or in Combination (ATAC) trial have demonstrated that the third-generation, selective aromatase inhibitor (AI) anastrozole ('Arimidex') is a suitable alternative adjuvant therapy for postmenopausal women with hormone receptor-positive disease. After recurrence or relapse on adjuvant endocrine therapy, responses to the sequential use of additional endocrine agents are common. The increase in the number of options now available for adjuvant therapy will have important implications for the selection of the optimal sequence of endocrine agents in the treatment of recurrent breast cancer. Menopausal status is an important factor in determining the endocrine therapy that a patient receives. For premenopausal women, tamoxifen and/or a luteinizing hormone-releasing hormone agonist such as goserelin ('Zoladex') are both options for adjuvant endocrine treatment. After progression on adjuvant and first-line tamoxifen, ovarian ablation is an appropriate second-line therapy. For premenopausal women who have undergone ovarian ablation, the use of third-line therapy with an AI becomes possible. For postmenopausal women, a wide choice of endocrine treatment options is available and an optimal sequence has yet to be determined. Options for first-line therapy of metastatic disease include an AI for women who have received adjuvant tamoxifen or tamoxifen for patients who have received adjuvant anastrozole. In addition, data suggest that fulvestrant ('Faslodex'), a novel estrogen receptor (ER) antagonist that downregulates the ER protein and has no known agonist effects, is a promising therapeutic option that has shown efficacy in the treatment of postmenopausal women with advanced breast cancer. Other agents that may be used in the sequence include the steroidal AI exemestane and the progestin megestrol acetate. The widening range of adjuvant endocrine options therefore represents an opportunity to prolong patient benefits in the treatment of hormone receptor-positive breast cancer, and will require the further refinement of the optimal sequence of endocrine agents for the treatment of recurrent breast cancer.

Anastrozole↗
PubMed2003

Phase I trial of uracil-ftorafur, leucovorin, and etoposide: an active all-oral regimen for metastatic breast cancer.

PURPOSE: To determine the maximum tolerated doses, toxicities, and therapeutic effect of an oral chemotherapy regimen consisting of uracil-ftorafur, etoposide, and leucovorin for metastatic breast cancer. PATIENTS AND METHODS: The regimen consists of 28-day cycles of uracil-ftorafur, etoposide, and leucovorin administered orally on days 1-14. The dose of etoposide was fixed at 50 mg/m2/day, and uracil-ftorafur was escalated in 50 mg/m2/day increments from 200 to 350 mg/m2. Leucovorin, was used at a dose of 90 mg/day. Eligibility criteria required prior treatment with a taxane or anthracycline. RESULTS: A total of 23 patients were enrolled. Twenty patients are assessable for toxicity and 16 patients are assessable for response. All non-hematologic toxicities were grade 1 or 2. Three hematologic dose-limiting toxicities (DLTs) were observed. Partial responses were seen in 6 of 16 (37.5%, 95% confidence interval 15%, 85%) of assessable patients with durations ranging from 4 to 20 months. Stable disease was observed in 4 of 16 (25%) of patients with durations from 4 to 12 months. Median time to progression was 10.5 months. An intent to treat analysis revealed a response of 26%. CONCLUSION: The recommended dose and schedule of this combination is uracil-ftorafur 350 mg/m2, leucovorin 90 mg/day, and etoposide 50 mg/m2 for two consecutive weeks in a 4-week cycle. This all-oral regimen is well tolerated and demonstrates encouraging efficacy in a cohort of heavily pretreated patient with metastatic breast cancer.

Adenocarcinoma↗