Initial Palliative Treatment Research Articles

Angioplasty with ductal stent: experience at Garrahan Hospital

To describe and evaluate the outcomes of ductal angioplasty with stent placement at a single high-complexity center during the period 2016-2022. A retrospective descriptive cross-sectional study was conducted, including patients under 3 months of age who underwent ductal stent implantation as initial palliative treatment. Demographic, clinical, and anatomical data were collected before the intervention. Mortality, intra- and post-procedural complications, need for re-intervention, intensive care requirements, and hospital stay were recorded. The characteristics at the time of definitive surgery are described. Discrete variables are presented as percentages, and continuous variables are presented with their medians and respective interquartile ranges. Twenty patients who underwent this treatment were reviewed, revealing a success rate of 80%. Complications due to stent dysfunction required surgical resolution. 95% of patients were dischargedfrom the institution after the procedure, and 17 patients reached a second definitive surgical stage. Three patients died afterthe procedure, but with no direct relation to it. Indications for ductal angioplasty with stent as an alternative treatment to systemic-pulmonary anastomosis by surgery are not yet fully defined; the strategy represents a valid alternative in appropriately selected patients. The presented experience shows results similar to international reference centers.

Bidirectional glenn surgery without palliative pulmonary artery banding in univentricular heart with unrestricted pulmonary flow. Retrospective multicenter experience

BackgroundAlthough pulmonary artery banding (PAB) has been generally acknowledged as an initial palliative treatment for patients having single ventricle (SV) physiology and unrestrictive pulmonary blood flow (UPBF), it may result in unfavorable outcomes. Performing bidirectional Glenn (BDG) surgery without initial PAB in some selected cases may avoid the complications associated with PAB and reduce the number of operative procedures for these patients. This research aimed to assess the outcome of BDG surgery performed directly without doing initial PAB in patients with SV-UPBF.MethodsThis Multicenter retrospective cohort includes all patients with SV-UPBF who had BDG surgery. Patients were separated into two groups. Patients in Group 1 included patients who survived till they received BDG (20 Patients) after initial PAB (28 patients), whereas patients in Group 2 got direct BDG surgery without first performing PAB (16 patients). Cardiac catheterization was done for all patients before BDG surgery. Patients with indexed pulmonary vascular resistance (PVRi) ≥ 5 WU.m2 at baseline or > 3 WU.m2 after vasoreactivity testing were excluded.ResultsCompared with patients who had direct BDG surgery, PAB patients had a higher cumulative mortality rate (32% vs. 0%, P = 0.016), with eight deaths after PAB and one mortality after BDG. There were no statistically significant differences between the patient groups who underwent BDG surgery regarding pulmonary vascular resistance, pulmonary artery pressure, postoperative usage of sildenafil or nitric oxide, intensive care unit stay, or hospital stay after BDG surgery. However, the cumulative durations in the intensive care unit (ICU) and hospital were more prolonged in patients with BDG after PAB (P = 0.003, P = 0.001respectively).ConclusionDirect BDG surgery without the first PAB is related to improved survival and shorter hospital stays in some selected SV-UPBF patients.

Abstract P1-16-06: In real world, a high percentage of premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer receive chemotherapy as first-line treatment: A study of the National Cancer Center, China

Abstract Background: In this study, we aimed to observe initial palliative treatment choices and clinical outcomes for premenopausal hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer patients (MBC) in the Chinese population in real life.Methods: The China National Cancer Center database was used to identify 2194 MBC patients diagnosed between 2004 to 2015. Premenopausal patients with HR+ HER2- MBC were included. Clinicopathological features, initial palliative treatment choices and survival information were extracted. First-line progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared using the log-rank test. Prognostic factors associated with OS were analyzed using Cox regression model with 95% confidence interval (95%C.I.).Results: A total of 451 premenopausal patients meeting study criteria were identified. Median age was 44 years. The number of patients receiving chemotherapy alone, endocrine therapy and chemotherapy followed by endocrine therapy as initial palliative treatment strategy were 222(49.2%), 80 (17.7%), and 149 (33.0%), respectively. Patients receiving initial chemotherapy were more likely to be luminal B subtype, had more de novo stage IV disease than recurrent disease and had more liver metastasis, compared with patients receiving initial endocrine therapy. Both PFS and OS were significantly longer for chemotherapy-endocrine therapy group (median PFS 18.9 months and OS 75.0 months), than for endocrine therapy group (median PFS 11.7 months and OS 53.5 months). Chemotherapy alone group presented with worst survival outcomes (median PFS 7.1 months and OS 43.9 months). However, in multivariate analysis, none of the three treatment strategies were independently associated with PFS or OS.Conclusions: In real world, a high percentage of premenopausal patients with HR+ HER2- disease received chemotherapy as initial palliative treatment in China, which was not associated with worsened survival. This unexpected guideline non-adherence reflects the unmet need of establishing treatment guidelines specifically for premenopausal patients in the Chinese population. Further studies with larger sample size across China are needed to explore the relationship between this guideline non-adherence and clinical outcomes. Citation Format: Yiqun Li, Hongnan Mo, Xiuwen Guan, Shaoyan Lin, Zijing Wang, Yimeng Chen, Shanshan Chen, Qiao Li, Ruigang Cai, Jiayu Wang, Yang Luo, Ying Fan, Peng Yuan, Pin Zhang, Qing Li, Fei Ma, Binghe Xu. In real world, a high percentage of premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer receive chemotherapy as first-line treatment: A study of the National Cancer Center, China [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-16-06.

Real world initial palliative treatment patterns and clinical outcomes in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer: A study of the National Cancer Center, China

BackgroundTo observe whether guideline non-adherence in initial palliative treatment choices for premenopausal hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (MBC) patients result in worse clinical outcomes in the Chinese population. MethodsThe China National Cancer Center database was used to identify 2194 patients diagnosed between 2004 and 2015. A total of 451 premenopausal patients with HR + HER2- MBC were included. Clinicopathological features and survival information were extracted. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared using log-rank test. ResultsThe number of patients receiving initial chemotherapy, endocrine therapy and chemo-endocrine therapy were 222 (49.2%), 80 (17.7%), and 149 (33.0%), respectively. Patients receiving initial chemotherapy were more likely to be luminal B subtype, had more de novo stage IV disease and more liver metastasis, compared with patients receiving initial endocrine therapy. Both PFS and OS were significantly longer for chemo-endocrine therapy group (median PFS 18.9 months and OS 75.0 months), than for endocrine therapy group (median PFS 11.7 months and OS 53.5 months), and chemotherapy group (median PFS 7.1 months and OS 43.9 months). In multivariate analysis, none of the three treatment strategies were independently associated with PFS or OS. ConclusionIn real world, a high percentage of premenopausal patients with HR + HER2- disease received chemotherapy as initial palliative treatment in China, which was not associated with worsened survival. Further studies with larger sample size across China are needed to explore the relationship between this guideline non-adherence and clinical outcomes.

Impact of multidisciplinary tumor board discussion on palliation of patients with esophageal or gastro-esophageal junction cancer: a population-based study

Background: The Dutch guidelines for esophageal and gastro-esophageal junction (GEJ) cancer recommend discussion of patients by a multidisciplinary tumor board (MDT). Despite this recommendation, one previous study in the Netherlands suggested that therapeutic guidance was missing for palliative care of patients with esophageal cancer. The aim of the current study was therefore to assess the impact of an MDT discussion on initial palliative treatment and outcome of patients with esophageal or GEJ cancer.Material and methods: The population-based Netherlands Cancer Registry was used to identify patients treated for esophageal or GEJ cancer with palliative intent between 2010 and 2017 in 7 hospitals. We compared patients discussed by the MDT with patients not discussed by the MDT in a multivariate analysis. Primary outcome was type of initial palliative treatment. Secondary outcome was overall survival.Results: A total of 389/948 (41%) patients with esophageal or GEJ cancer were discussed by the MDT before initial palliative treatment. MDT discussion compared to non-MDT discussion was associated with more patients treated with palliative intent external beam radiotherapy (38% vs. 21%, OR 2.7 [95% CI 1.8–3.9]) and systemic therapy (30% vs. 23%, OR 1.6 [95% CI 1.0–2.5]), and fewer patients treated with stent placement (4% vs. 12%, OR 0.3 [95% CI 0.1–0.6]) and best supportive care alone (12% vs. 33%, OR 0.2 [95% CI 0.1–0.3]). MDT discussion was also associated with improved survival (169 days vs. 107 days, HR 1.3 [95% CI 1.1–1.6]).Conclusion: Our study shows that MDT discussion of patients with esophageal or GEJ cancer resulted in more patients treated with initial palliative radiotherapy and chemotherapy compared with patients not discussed by the MDT. Moreover, MDT discussion may have a positive effect on survival, highlighting the importance of MDT meetings at all stages of treatment.

Melanoma primario de pene

Descripción caso clínico: Masculino de 54 años de edad, sin antecedentes de importancia, valorado por síntomas obstructivos del tracto urinario inferior. Presenta fimosis y se palpa en glande lesión pétrea, se realiza incisión dorsal de prepucio teniendo como hallazgo tumor en glande de aspecto verrugoso, color negro, consistencia pétrea. El tratamiento consistió en penectomía total. Presenta progresión de la actividad tumoral hepática, esplénica y ganglionar inguinal izquierdo además de lesiones blásticas a nivel de l4, t7 y t9. Tratado inicialmente de forma paliativa con temozolamida y posteriormente con inf alfa 2b y ácido zoledrónico. El paciente fallece a los 16 meses de diagnóstico.
 Relevancia: El melanoma de pene neoplasia cutánea maligna agresiva, de rápida progresión y con alta mortalidad, derivado de la proliferación de melanocitos atípicos representa menos del 1% de los casos de cáncer de pene y menos del 0.2% de todos los melanomas. Se han reportado alrededor de 200 casos en la literatura.
 Implicaciones clínicas: No existe tratamiento estandarizado, el tratamiento es quirúrgico mediante penectomía total, sin embargo, no existe un estándar de tratamiento. La opción de tratamiento más racional parece ser una cirugía radical si es posible junto con la terapia adyuvante.
 Conclusiones: El melanoma de pene neoplasia cutánea maligna de mal pronóstico por su gran capacidad de producir metástasis y rápida diseminación principalmente por vía linfática. La quimioterapia y radioterapia son solo paliativas o adyuvantes con resultados variables.

Does guideline non-adherence result in worse clinical outcomes for hormone receptor-positive and HER2-negative metastatic breast cancer in premenopausal women?: result of an institution database from South Korea

BackgroundIn this study, we observe the patterns initial palliative treatment for premenopausal patients with HR-positive/HER2-negative MBC and determine if nonadherence to clinical guidelines are associated with worse clinical outcomes in terms of progression-free survival (PFS) and overall survival (OS) in the South Korean population.MethodsA retrospective review was performed for premenopausal patients diagnosed with HR-positive/HER2-negative MBC between October 1997 and May 2016 who received palliative systemic treatments at a large tertiary medical center. Survival outcomes were analyzed according to the palliative treatment received prior to disease progression.ResultsThe review identified a total of 272 premenopausal patients meeting study criteria, whose median age was 39 years. Endocrine therapy was the initial treatment in 137 patients (Group 1) with chemotherapy as initial treatment in 135 patients. In the latter group, chemotherapy was continued in 78 patients (Group 2), whereas chemotherapy was switched to endocrine treatment in 57 patients prior to any disease progression (Group 3). Both PFS and OS were significantly longer for chemotherapy-endocrine therapy (median PFS 18.2 months and OS 85.2 months) than for chemotherapy-alone (median PFS 12.6 months and OS 45.5 months) or endocrine therapy-alone (median PFS 7.0 months and OS 57.3 months) (all p values < 0.01). In multivariate analysis, chemotherapy-endocrine therapy was an independent predictive value for improved PFS and OS (hazard ratio [HR] 0.33, 95% CI 0.20–0.52, p < 0.001; HR 0.38, 95% CI 0.19–0.73, p = 0.004).ConclusionsIn our study population, chemotherapy alone was not objectively inferior to endocrine therapy as the initial palliative treatment. In addition, chemotherapy followed by endocrine therapy was associated with objective higher response rate than endocrine therapy alone. Further studies should explore the relationship between non-adherent treatment patterns and patient outcomes across the largely premenopausal breast cancer populations across Asian countries.

Is Aortic Valve Leaflet Morphology Predictive of Outcome in Pediatric Aortic Valve Stenosis?

Initial palliative treatment of congenital aortic valve stenosis consists of either surgical commissurotomy or transcatheter balloon valvuloplasty. The basis for selection of primary approach usually is ill defined. It was hypothesized that aortic valve characteristics may be helpful in directing choice of intervention. This study assesses the impact of valve morphology on time to reintervention after catheter- or surgical-based therapy. A retrospective review of preprocedural echocardiographic aortic outflow characteristics was compared with outcomes of primary surgical or balloon valve interventions. Characteristics studied included (1) annular dimension; (2) leaflet number; (3) leaflet excursion; and (4) degree of leaflet coaptation. Patients included those <20 years with a primary diagnosis of aortic stenosis (AS) and no other hemodynamically significant lesions at our institutions from 2000 to 2011. A total of 102 patients were included, 31 classified as having critical and 71 as having noncritical aortic stenosis. Of the patients, 79 were male, and 50 underwent primary catheter intervention. Echo parameters were compared with procedural outcome as defined by death or need for reintervention. Receiver operator curves were utilized to determine the point within each morphologic feature where the greatest difference occurred. This was utilized as the distinguishing point within each the morphologic group. Analysis was conducted separately for critical and noncritical aortic stenosis. Kaplan-Meier analysis demonstrated no significant difference in time to reintervention or death whether initial palliation consisted of surgical commissurotomy or balloon valvuloplasty with respect to any of the morphologic characteristics studied. Patients with AS do equally well with surgical commissurotomy or balloon valvuloplasty as initial palliation. This holds true for those with either critical or noncritical aortic stenosis. Valve morphology did not help in selection of initial palliative strategy. Current technologies should enable an improved selection of initial palliative approach through thoughtful, randomized trials.

Impact of carcinomatosis and ascites status on long-term outcomes of palliative treatment for patients with gastric outlet obstruction caused by unresectable gastric cancer: stent placement versus palliative gastrojejunostomy

Self-expandable metal stent (SEMS) placement and palliative gastrojejunostomy (GJJ) are palliative treatment options for malignant gastric outlet obstruction. To compare clinical outcomes of palliative treatments for gastric outlet obstruction caused by unresectable gastric cancer. Retrospective study. University-affiliated tertiary-care hospital in the Republic of Korea. Two hundred fifty-six patients with gastric outlet obstruction caused by unresectable gastric cancer. SEMS placement and palliative GJJ. Patency duration and overall survival duration. In total, 217 and 39 patients underwent SEMS placement and palliative GJJ, respectively, as an initial palliative treatment. Treatment modality affected reobstruction after clinical success (hazard ratio [HR] [95% confidence interval {CI}], 0.5 [0.3-0.8] of palliative GJJ). In addition, carcinomatosis with ascites was an independent associated factor of clinical success and reobstruction (HR [95% CI], 0.3 [0.1-0.7] and 1.4 [1.0-2.0], respectively). In a subgroup of patients with good performance who had neither carcinomatosis nor ascites, patency duration and overall survival duration did not differ between the 2 groups (P= .079 and P= .290, respectively). In patients with good performance who had carcinomatosis without ascites, patency duration was longer in the palliative GJJ group than in the SEMS placement group (P= .016). Overall survival, however, did not differ between the 2 groups (P= .062). In a subgroup of patients with good performance who had carcinomatosis with ascites, both patency duration and overall survival were longer in the palliative GJJ group than in the SEMS placement group (P= .007 and P= .012, respectively). Nonrandomized, retrospective study. Long-term clinical outcomes of the palliative treatment modality for gastric outlet obstruction caused byunresectable gastric cancer were affected by carcinomatosis and ascites status.

Palliative thoracic radiotherapy in lung cancer: An American Society for Radiation Oncology evidence-based clinical practice guideline

PurposeTo provide guidance to physicians and patients with regard to the use of external beam radiotherapy, endobronchial brachytherapy, and concurrent chemotherapy in the setting of palliative thoracic treatment for lung cancer, based on available evidence complemented by expert opinion. Methods and MaterialsA Task Force authorized by the American Society for Radiation Oncology (ASTRO) Board of Directors synthesized and assessed evidence from 3 systematic reviews on the following topics: (1) dose fractionation in thoracic external beam radiotherapy (EBRT); (2) clinical utility of initial and salvage endobronchial brachytherapy (EBB); and (3) use of concurrent chemotherapy (CC) with palliative thoracic radiotherapy. Practice guideline recommendations were produced and are contained herein. ResultsStudies suggest that higher dose/fractionation palliative EBRT regimens (eg, 30 Gy/10 fraction equivalent or greater) are associated with modest improvements in survival and total symptom score, particularly in patients with good performance status. As these improvements are associated with an increase in esophageal toxicity, various shorter EBRT dose/fractionation schedules (eg, 20 Gy in 5 fractions, 17 Gy in 2 weekly fractions, 10 Gy in 1 fraction), which provide good symptomatic relief with fewer side effects, can be used for patients requesting a shorter treatment course and/or in those with a poor performance status. No defined role for EBB in the routine initial palliative treatment of chest disease has been demonstrated; however, EBB can be a reasonable option for the palliation of endobronchial lesions causing obstructive symptomatology including lung collapse, or for hemoptysis after EBRT failure. The integration of concurrent chemotherapy with palliative intent/fractionated radiotherapy is not currently supported by the medical literature. ConclusionThis Guideline is intended to serve as a guide for the use of EBRT, EBB, and CC in thoracic palliation of lung cancer outside the clinical trial setting. Further prospective clinical investigations with relevant palliative endpoints into the respective roles of EBB and CC/targeted therapy in the thoracic palliation of lung cancer are warranted, given the current state of the medical literature in these areas.

Salvage Surgery Following Downstaging of Unresectable Hepatocellular Carcinoma—A Strategy to Increase Resectability

Surgical resection with complete extirpation of the tumor gives the best chance of a cure for patients with hepatocellular carcinoma (HCC). However, the resectability of HCC at the time of diagnosis is low (10-30%). This article reviews the use of salvage surgery following tumor downstaging to treat unresectable HCC. A Medline search was undertaken from 1966 to 2005 to identify articles using the keywords "liver neoplasm," "hepatocellular carcinoma," "tumor downstaging," and "unresectable." Additional papers were identified by a manual search of the references from the key articles. Eight to eighteen percent of patients with unresectable HCC responded well enough to the initial palliative treatment to downstage HCC to allow salvage surgical resection. The reported five-year survival rate after salvage surgery following tumor downstaging varied from 24.9 to 57%. Although it is still unknown whether the outcome of salvage surgery following tumor downstaging is comparable to those of resectable tumors after primary resection, one clear message is that salvage surgery following tumor downstaging gives good long-term results and the possibility of a cure in a proportion of patients with unresectable HCC. The role of salvage surgery after tumor downstaging in improving disease-free and overall survival in patients with unresectable HCC should be investigated further by prospective randomized controlled trials.

Targeting the estrogen receptor in clinical breast cancer1

Breast cancer is the most common cancer in women worldwide with more than 500,000 new cases diagnosed and 250,000 deaths annually. Treatment directed to inhibiting the action of the estrogen receptor (ER) represents one of the earliest examples of a successful targeted therapy for clinical breast cancer. We know that the ER functions as a transcription factor which controls estrogen-regulated genes important for the development, growth, and progression of breast cancer. The current, initial palliative treatment for women with estrogen-sensitive breast cancer is the antiestrogen tamoxifen. Patients whose tumors progress after responding to tamoxifen can achieve further responses from subsequent second-line therapy with agents such as the potent aromatase inhibitors, which have recently shown promise as potential first-line therapies. Our present understanding of the molecular mechanisms of action of ER, and its interaction downstream of various polypeptide growth factors and their receptors, cell survival conduits, and various protein kinase signaling pathways, has the potential to greatly increase our armory of hormonally-targeted strategies for the treatment and reversal of endocrine resistance. Therefore, combined directed therapies to these growth factor-triggered pathways, along with treatments directly targeting the ER, may provide more optimum treatment strategies in the future.

Open Access Follow-up for Lung Cancer: Patient and Staff Satisfaction

The majority of patients with lung cancer have incurable disease from presentation and a survival measured in months. Treatments offered to these patients are aimed at the palliation of symptoms with either radiotherapy or chemotherapy, or with supportive measures. It has been traditional to offer regular outpatient follow-up after initial palliative treatment. Further treatment options, which may be limited, are usually reserved for the recurrence of troublesome symptoms. A pilot ‘open access’ lung cancer clinic has been set up. Rather than have regular follow-up at the hospital, patients who have completed initial palliative treatments are discharged to the community with follow-up by their general practitioner and Macmillan nurse. Review at the open access clinic can be arranged at short notice if requested by the patient, carers, general practitioner or Macmillan nurse. The outcomes and level of satisfaction of patients, their relatives and staff to this method of follow-up were found to be positive. Open access follow-up may be useful for many patients after the completion of initial palliative treatment.

Metallic stents in malignant biliary obstruction: prospective long-term clinical results.

The purpose of this prospective study was to evaluate the long-term clinical efficacy of metallic stents when used as the initial palliative treatment of patients with inoperable malignant biliary obstruction. From August 1991 through May 1995, 100 consecutive patients with malignant biliary obstruction were treated with percutaneous placement of metallic stents. The causes of obstruction were bile duct carcinoma (n = 50), pancreatic carcinoma (n = 17), gallbladder carcinoma (n = 6), hepatocellular carcinoma (n = 2), and metastatic lymphadenopathy in the hepatoduodenal ligament (n = 25). We used 123 stents: 64 Gianturco Z stents, 39 Hanaro spiral stents, 16 Wallstents, two tantalum Strecker stents, one Endocoil stent, and one Memotherm nitinol stent. Every 3 months we followed up all patients except those who died. The average length of follow-up was 220 days (range, 4-1125 days). Patient survival and stent patency rates were estimated by life-table analysis. The median length of survival for the entire patient group was 246 days: 25-week and 50-week survival rates were 62% and 25%, respectively. We found no statistically significant difference in the median length of survival between patients with hilar obstruction (256 days) and patients with common bile duct (CBD) obstruction (227 days). Patients with bile duct carcinoma had longer median survival (269 days) than did patients with other conditions (197 days). The overall median length of patency for all stents was 360 days; the 25-week and 50-week patency rates were 81% and 53%, respectively. The stent patency rate at the median length of survival was 71%. The median length of stent patency in patients with hilar obstruction (617 days) was nearly double that of patients with CBD obstruction (324 days). However, the median length of stent patency in patients with bile duct carcinoma showed no statistically significant difference from the median length in patients with other disease. Four patients (4%) died within 1 month after stent placement. Twenty-one patients (21%) developed recurrent jaundice or cholangitis. In order of frequency, the causes of recurrent jaundice were tumor overgrowth, incrustation of bile sludge, duodenal obstruction due to tumor invasion, stent impaction into the bile duct wall, stent malposition, and tumor ingrowth. Metallic stents showed a favorable patency rate with regard to patient survival. In patients with hilar obstruction, the clinical efficacy of metallic stents was superior to that in patients with CBD obstruction. We believe that placement of metallic stents is the procedure of choice for palliation of malignant biliary obstruction.

Mitoxantrone, 5‐fluorouracil, and high dose leucovorin (NFL) versus intravenous cyclophosphamide, methotrexate, and 5‐fluorouracil (CMF) in first‐line chemotherapy for patients with metastatic breast carcinoma

Previous Phase II studies using the combination of mitoxantrone, 5-fluorouracil, and high dose leucovorin (NFL) in the treatment of metastatic breast carcinoma have shown this regimen to be active and well tolerated. In this randomized Phase II study, the authors compared the NFL regimen with a standard CMF regimen in the first-line therapy of patients with metastatic breast carcinoma. One hundred twenty-eight women receiving their first chemotherapy for metastatic breast carcinoma were entered into this randomized study. Sixty-four patients were treated with NFL: mitoxantrone 12 mg/m2 IV on Day 1; leucovorin 300 mg IV over 30-60 minutes on Days 1, 2, and 3, immediately preceding administration of 5-fluorouracil; and 5-fluorouracil 350 mg/m2 IV bolus on Days 1, 2, and 3. Sixty-four patients received CMF: cyclophosphamide 600 mg/m2 IV on Day 1; methotrexate 40 mg/m2 IV on Day 1; and 5-fluorouracil 600 mg/m2 IV on Day 1. Both regimens were repeated at 21-day intervals; responding patients received at least 8 courses. Patients treated with NFL had a higher response rate than patients treated with the CMF regimen (45% vs. 26%, respectively; P = 0.021). Median duration of response was 9 months with NFL and 6 months with CMF (P = 0.10); 11 patients had long responses (>12 months) with NFL versus 4 patients with CMF (P = 0.06). Median survival was similar for both groups. Both regimens were well tolerated, with infrequent Grade 3 or 4 toxicities. NFL is an active, well-tolerated regimen for the treatment of metastatic breast carcinoma; it produced a higher response rate than the CMF regimen used in this study. Although more intense CMF regimens or regimens containing doxorubicin would likely increase the response rate, they would almost certainly do so with the consequence of greater toxicity as compared with NFL. NFL is an excellent initial palliative treatment option for elderly patients or patients who have exhibited poor tolerance for other chemotherapy regimens.