Inflammatory breast cancer defined: proposed common diagnostic criteria to guide treatment and research.

PURPOSE: Inflammatory breast cancer is a deadly and aggressive type of breast cancer. A key challenge relates to the need for a more detailed, formal, objective definition of IBC, the lack of which compromises clinical care, hampers the conduct of clinical trials, and hinders the search for IBC-specific biomarkers and treatments because of the heterogeneity of patients considered to have IBC. METHODS: Susan G. Komen, the Inflammatory Breast Cancer Research Foundation, and the Milburn Foundation convened patient advocates, clinicians, and researchers to review the state of IBC and to propose initiatives to advance the field. After literature review of the defining clinical, pathologic, and imaging characteristics of IBC, the experts developed a novel quantitative scoring system for diagnosis. RESULTS: The experts identified through consensus several "defining characteristics" of IBC, including factors related to timing of onset and specific symptoms. These reflect common pathophysiologic changes, sometimes detectable on biopsy in the form of dermal lymphovascular tumor emboli and often reflected in imaging findings. Based on the importance and extent of these characteristics, the experts developed a scoring scale that yields a continuous score from 0 to 48 and proposed cut-points for categorization that can be tested in subsequent validation studies. CONCLUSION: To move beyond subjective 'clinical diagnosis' of IBC, we propose a quantitative scoring system to define IBC, based on clinical, pathologic, and imaging features. This system is intended to predict outcome and biology, guide treatment decisions and inclusion in clinical trials, and increase diagnostic accuracy to aid basic research; future validation studies are necessary to evaluate its performance.

A phase II feasibility study of palbociclib in combination with adjuvant endocrine therapy for hormone receptor-positive invasive breast carcinoma.

BACKGROUND: The CDK4/6 inhibitor palbociclib prolongs progression-free survival in hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer when combined with endocrine therapy. This phase II trial was designed to determine the feasibility of adjuvant palbociclib and endocrine therapy for early breast cancer. PATIENTS AND METHODS: Eligible patients with HR+/HER2- stage II-III breast cancer received 2 years of palbociclib at 125 mg daily, 3 weeks on/1 week off, with endocrine therapy. The primary end point was discontinuation from palbociclib due to toxicity, non-adherence, or events related to tolerability. A discontinuation rate of 48% or higher would indicate the treatment duration of 2 years was not feasible, and was evaluated under a binomial test using a one-sided α = 0.025. RESULTS: Overall, 162 patients initiated palbociclib; over half had stage III disease (52%) and most received prior chemotherapy (80%). A total of 102 patients (63%) completed 2 years of palbociclib; 50 patients discontinued early for protocol-related reasons (31%, 95% CI 24% to 39%, P = 0.001), and 10 discontinued due to protocol-unrelated reasons. The cumulative incidence of protocol-related discontinuation was 21% (95% CI 14% to 27%) at 12 months from start of treatment. Rates of palbociclib-related toxicity were congruent with the metastatic experience, and there were no cases of febrile neutropenia. Ninety-one patients (56%) required at least one dose reduction. CONCLUSION: Adjuvant palbociclib is feasible in early breast cancer, with a high proportion of patients able to complete 2 years of therapy. The safety profile in the adjuvant setting mirrors that observed in metastatic disease, with approximately half of the patients requiring dose-modification. As extended duration adjuvant palbociclib appears feasible and tolerable for most patients, randomized phase III trials are evaluating clinical benefit in this population. CLINICALTRIALS.GOV REGISTRATION: NCT02040857.

Randomized phase III study of docetaxel compared with paclitaxel in metastatic breast cancer.

PURPOSE: This randomized, controlled, multicenter, open-label, phase III study compared docetaxel versus paclitaxel in patients with advanced breast cancer that had progressed after an anthracycline-containing chemotherapy regimen. PATIENTS AND METHODS: Patients (n = 449) were randomly assigned to receive either docetaxel 100 mg/m2 (n = 225) or paclitaxel 175 mg/m2 (n = 224) on day 1, every 21 days until tumor progression, unacceptable toxicity, or withdrawal of consent. RESULTS: In the intent-to-treat population, both the median overall survival (OS, 15.4 v 12.7 months; hazard ratio [HR], 1.41; 95% CI, 1.15 to 1.73; P = .03) and the median time to progression (TTP, 5.7 months v 3.6 months; HR, 1.64; 95% CI, 1.33 to 2.02; P < .0001) for docetaxel were significantly longer than for paclitaxel, and the overall response rate (ORR, 32% v 25%; P = .10) was higher for docetaxel. These results were confirmed by multivariate analyses. The incidence of treatment-related hematologic and nonhematologic toxicities was greater for docetaxel than for paclitaxel; however, quality-of-life scores were not statistically different between treatment groups over time. CONCLUSION: Docetaxel was superior to paclitaxel in terms of OS and TTP. ORR was higher for docetaxel. Hematologic and nonhematologic toxicities occurred more frequently in the docetaxel group. The global quality-of-life scores were similar for both agents over time.

Randomized placebo-controlled study of recombinant human interleukin-11 to prevent chemotherapy-induced thrombocytopenia in patients with breast cancer receiving dose-intensive cyclophosphamide and doxorubicin.

PURPOSE: Thrombocytopenia may compromise cancer treatment, causing chemotherapy dose reductions, schedule alterations, or the need for platelet transfusions. We evaluated the efficacy and safety of recombinant human interleukin-11 (rhIL-11; Neumega, Genetics Institute, Inc, Cambridge, MA), a novel thrombopoietic growth factor, in reducing the need for platelet transfusions in patients who undergo dose-intensive chemotherapy. PATIENTS AND METHODS: Women with advanced breast cancer received cyclophosphamide (3,200 mg/m2) and doxorubicin (75 mg/m2) plus granulocyte colony-stimulating factor (G-CSF; 5 microg/kg/d). Patients were randomized to blinded treatment with placebo or 50 microg/kg/d rhIL-11 subcutaneously for 10 or 17 days after the first two chemotherapy cycles. RESULTS: Seventy-seven patients were randomized and constitute the intent-to-treat (ITT) population. Sixty-seven patients (the assessable subgroup) either completed both cycles without a major protocol violation (n = 62) or received a platelet transfusion before treatment was discontinued after the first cycle. In the ITT population, rhIL-11 significantly decreased the requirement for platelet transfusions; 27 of 40 (68%) patients who received rhIL-11 did not require transfusions, compared with 15 of 37 (41%) in the placebo group (P = .04). Treatment with rhIL-11 significantly reduced the total number of platelet transfusions required in the assessable subgroup (P = .03) and the time to platelet recovery to more than 50,000/microL in the second cycle (P = .01). Most adverse events associated with rhIL-11 were reversible, mild to moderate in severity, and likely related to fluid retention. CONCLUSION: rhIL-11 is safe and effective in reducing treatment-associated thrombocytopenia and the need for platelet transfusions in patients who undergo dose-intensive chemotherapy, and thus may permit chemotherapy to be administered as planned at intended doses and thereby maximize the potential for a successful outcome.

Targeting breast cancer through its microenvironment: current status of preclinical and clinical research in finding relevant targets.

It is increasingly evident that not only breast cancer cells, but also the tissue embedding these cells: the tumor microenvironment, plays an important role in tumor progression, metastasis formation and treatment sensitivity. This review focuses on the current knowledge of processes by which the microenvironment affects breast cancer, including formation of the metastatic niche, metabolic stimulation, stimulation of tumor cell migration, immune modulation, angiogenesis and matrix remodeling. The number of drugs targeting key factors in these processes is expanding, and the available clinical data is increasing. Therefore current strategies for intervention and prediction of treatment response are outlined. At present, targeting the formation of the metastatic niche and metabolic stimulation by the breast cancer microenvironment, are already showing clinical efficacy. Intervening in the stimulation of tumor cell migration and immune modulation by the microenvironment upcoming fields of great research interest. In contrast, targeting microenvironmental angiogenesis or matrix remodeling appears to be of limited clinical relevance in breast cancer treatment so far. Further research is warranted to optimize intervention strategies and develop predictive tests for the relevance of targeting involved factors within the microenvironment in order to optimally personalize breast cancer treatment.

Ifosfamide in the treatment of breast cancer.

Ifosfamide is an alkylating agent that has demonstrated efficacy in the treatment of several malignancies. Preclinical data also support non-cross-reactivity between cyclophosphamide and ifosfamide in several cell lines. These data suggest that ifosfamide may be highly effective in the salvage setting for breast cancer patients who have received previous treatment with cyclophosphamide. Unfortunately, the available data on ifosfamide use in advanced disease are derived from poorly designed studies that evaluated various patient populations and dosing schedules. This review examines the efficacy of ifosfamide in salvage therapy for breast cancer and emphasizes the need to determine the optimal dosing schedule for ifosfamide used as a single agent or in combination chemotherapy for advanced breast cancer.

Chemotherapeutic palliative approaches in the treatment of breast cancer.

The palliative approach to the treatment of metastatic breast cancer deserves discussion because of the numerous patients diagnosed with this disease. Approximately 10% of the greater than 180,000 women diagnosed with breast cancer each year will present with metastatic disease, and an additional 50% to 70% will eventually relapse. The clinician must consider the treatment toxicity, efficacy, and impact on quality of life to arrive at the optimal therapeutic decision. The following discussion will provide an overview of palliative treatment options, including single-agent and combination chemotherapy, as well as new alternative drugs, such as paclitaxel and vinorelbine. Treatment toxicity and its impact on quality of life will be emphasized.

The influence of young age on outcome in early stage breast cancer.

PURPOSE: To assess the impact of young age on outcome in women with early stage breast cancer undergoing conservative surgery and radiation. METHODS AND MATERIALS: Between 1981 and 1991, 980 patients with Stage I and II breast cancer underwent excisional biopsy, axillary dissection, and radiation. The median follow-up was 4.6 years, with a range of 1 month to 11 years. The patients were divided into three groups, based on age at the time of diagnosis: (a) age < or = 35 years--64 patients, (b) age 36-50 years--363 patients, and (c) age > 50 years--553 patients. The comparability of the groups was assessed in terms of clinical factors (tumor size and race), histopathologic factors (histologic subtype, final resection margin, estrogen and progesterone receptor status, pathologic nodal status), and treatment related factors (reexcision, median total dose to the primary, region(s) treated with radiation, and the use of adjuvant systemic chemotherapy and/or tamoxifen). Outcome was evaluated for overall, relapse-free, and cause-specific survival and patterns of first failure (breast, regional nodes, and distant metastasis). RESULTS: There were no significant differences among the three groups in terms of race, clinical tumor size, pathology of the primary tumor, pathologic nodal status, final margin of resection, progesterone receptor status, median total dose to the primary tumor, or the regions treated. However, younger women were significantly more likely to have estrogen receptor negative tumors, undergo reexcision, and receive adjuvant systemic chemotherapy without tamoxifen. Younger women were found to have a statistically significantly decreased 8-year actuarial relapse-free survival (53% vs. 67% vs. 74%, p = 0.009), cause-specific survival (73% vs. 84% vs. 90%, p = 0.02), freedom from distant metastasis (76% vs. 75% vs. 83%, p = 0.02), and a significantly increased risk of breast recurrence (24% vs. 14% vs. 12%, p = 0.001), and regional node recurrence (7% vs. 1% vs. 1%, p = 0.0002). The patients were further divided on the basis of their pathologic nodal status. There were no statistically significant differences among the three age groups for axillary node-positive patients for overall survival (75% vs. 80% vs. 74%), relapse-free survival (73% vs. 73% vs. 62%), cause-specific survival (76% vs. 85% vs. 80%), and freedom from distant metastasis (75% vs. 75% vs. 72%), or breast recurrence (0% vs. 9% vs. 6%). The findings were identical when the analysis was restricted to node-positive patients who received chemotherapy. However, for axillary node-negative women, young age was associated with a statistically significant decreased overall survival (71% vs. 83% vs. 92%), relapse-free survival (51% vs. 65% vs. 76%), cause-specific survival (71% vs. 86% vs. 93%), freedom from distant metastasis (77% vs. 76% vs. 88%), and a statistically significant increased risk of breast recurrence (40% vs. 16% vs. 13%), and regional node recurrence (3% vs. 1% vs. 0%). The risk of a breast recurrence in axillary node-negative young women was decreased by the addition of adjuvant systemic chemotherapy but not by the use of reexcision. CONCLUSIONS: The present analysis demonstrates that young women with early stage breast cancer do significantly worse when compared to older women in terms of relapse-free survival, cause-specific survival, distant metastasis and breast and regional node recurrence. However, the adverse effect of young age on outcome appears to be limited to the node-negative patients. These findings suggest that node-negative early stage breast cancer in young women is a more aggressive disease, with an increased risk for all patterns of failure and a decreased survival.

Variables associated with the platelet count 6 weeks after autologous peripheral blood progenitor cell transplantation.

While abundant data exist documenting variables associated with early platelet engraftment after autologous PBPC transplantation, data concerning later sustained platelet engraftment is sparse. We retrospectively examined a series of 80 patients undergoing autologous PBPC transplantation with respect to their platelet count 6 weeks after transplant. Underlying diagnoses included breast cancer (n = 33), non-Hodgkin's lymphoma (n = 32), Hodgkin's disease (n = 9), and other hematologic malignancies (n = 6). Patients received G-CSF for PBPC mobilization and collected a target threshold number of 2.0 x 10(6) CD34+ cells per kilogram. A univariate analysis revealed that a diagnosis of breast cancer, fewer courses of prior chemotherapy, younger age and complete remission were associated with a higher 6-week platelet count. Additionally, the ability to collect the threshold number of CD34+ with fewer sessions of leukapheresis was also associated with a higher 6-week platelet count. The platelet count and the white blood cell count at the initiation of PBPC collection was also associated with a higher 6-week platelet count. A multivariate analysis revealed a higher platelet count on the first day of pheresis, fewer phereses required to collect 2 x 10(6) CD34+ cells per kilogram, and a diagnosis of breast cancer were all associated with a higher 6-week post-transplant platelet count. Seven patients failed to reach a 6-week platelet count of 30 x 10(9)/l and an additional five patients had a platelet count of 30-50 x 10(9)/l. We conclude that underlying clinical characteristics, as well as hematologic variables at the time of PBPC collection, influence later, sustained platelet engraftment. A percentage of patients have poor sustained platelet engraftment and may be candidates for new cytokines that specifically target megakaryocyte growth and development.

Platelet transfusion requirements during autologous peripheral blood progenitor cell transplantation correlate with the pretransplant platelet count.

The use of primed peripheral blood progenitor cells (PBPC) has improved platelet engraftment following autologous bone marrow/PBPC transplantation (ABMT). The thrombocytopenia associated with ABMT generally lasts 14-18 days, and is associated with variable platelet transfusion requirements. Little, if any, data exist examining prognostic parameters for platelet transfusion requirements during autologous transplantation. We retrospectively examined 286 consecutive patients undergoing autologous transplantation from 1 January 1994 to 1 June 1996 with respect to platelet engraftment and platelet transfusion requirements. One hundred and fifty four patients were transplanted for breast cancer (54%), 72 for non-Hodgkin's lymphoma (25%), 35 for Hodgkin's disease (12%), 13 for acute leukemia (5%), eight for myeloma (3%), and four for other malignancy (1%). The median age was 44. All patients received cytokine priming, usually with G-CSF, for the procurement of PBPC. The median number of CD34+ cells collected was 4.3 x 10(6)/kg. All patients received a chemotherapeutic preparative regimen and all received an autologous transplant using PBPC alone. The median time to a platelet count of 20 x 10(9)/l was 13 days. Patients beginning the transplant with a less than normal platelet count (less than 150 x 10(9)/l) engrafted in 17 days, and received a median number of seven platelet transfusions, as compared with platelet engraftment of 12 days, and four platelet transfusions, for patients beginning the transplant with a normal platelet count (P = 0.001). Both groups of patients received an equivalent dose of CD34+ cells. We conclude that thrombocytopenia at the initiation of autologous transplantation is associated with increased platelet transfusion requirements, independent of the dose of CD34+ cells infused.

Phase 1 study of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) in breast cancer patients after autologous peripheral blood progenitor cell (PBPC) transplantation.

Forty-seven patients with stage II, III, or IV breast cancer undergoing autologous peripheral blood progenitor cell (PBPC) transplantation were randomized to placebo (n = 13) or to one of five sequential dose cohorts of pegylated (PEG) recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) (1.0, 2.5, 5.0, 7.5, or 10.0 microg/kg/day) (n= 34). Blinded study drug was started on the day of transplantation and was continued until the platelet count was > or =100 x 109/l or a maximum of 21 days. PBPCs were mobilized with filgrastim (r-metHuG-CSF) and all patients received filgrastim starting on day +2 after transplantation. The nadir platelet count was not affected by treatment. The median time to platelet recovery was 11 and 12 days for the placebo and combined PEG-rHuMGDF groups, respectively. No trends in adverse events suggested dose- or treatment-related toxicity. Two patients withdrew from the study because of an adverse event (allergic reaction in the 7.5 microg/kg group) probably related to study drug, and veno-occlusive disease (VOD) (in the 5 microg/kg group) which was felt not to be related to study drug by the investigator. No patients developed neutralizing antibodies to MGDF. Day +21 and day +28 platelet counts were higher in the group receiving PEG-rHuMGDF (246 vs 148 x 109/l and 299 vs 145 x 109/l, respectively; both P < 0. 05). PEG-rHuMGDF up to 10 microg/kg/day was well tolerated. In this study, there was no effect of study drug on initial platelet engraftment at the doses studied. However, the efficacy of other doses is unknown.

G-CSF post-autologous progenitor cell transplantation: a randomized study of 5, 10, and 16 micrograms/kg/day.

G-CSF is routinely administered after autologous bone marrow or peripheral blood progenitor cell transplantation to enhance neutrophil engraftment. However, many different doses of G-CSF have been described with no clear consensus on the most cost-effective dose. We performed a prospective randomized trial examining the efficacy of three different doses of G-CSF post-autologous transplant (5, 10, or 16 micrograms/kg/day). Fifty-seven consecutive patients with breast cancer (n = 30), non-Hodgkin's lymphoma (n = 16), Hodgkin's disease (n = 6), multiple myeloma (n = 2), acute leukemia (n = 2), and testicular cancer (n = 1) were randomized, with 19 patients enrolled in each of the three treatment groups. All patients underwent a high-dose chemotherapy preparative regimen and received an autologous peripheral blood progenitor cell (PBPC) transplant (without bone marrow), with G-CSF beginning on day 0. There was no difference in time to neutrophil engraftment among the three treatment groups (mean 10.2 to 10.8 days). There is a trend towards earlier platelet engraftment in the patient group receiving 5 microgram/kg/day of G-CSF. The total cost of G-CSF by dose group was $2900, $4400, and $6500 per patient. We conclude that there was no advantage to the use of higher doses of G-CSF after autologous transplantation, and that lower doses are associated with lower costs.

Delayed G-CSF after autologous progenitor cell transplantation: a prospective randomized trial.

G-CSF is given after autologous progenitor cell transplantation to accelerate neutrophil engraftment. Historically, G-CSF has been started on the day of progenitor cell infusion. To study the timing of the initiation of G-CSF after autologous peripheral blood progenitor cell (PBPC) transplantation, we conducted a prospective, randomized trial comparing the initiation of G-CSF therapy on day 0, day +3 or day +5 after autologous PBPC transplantation. Seventy patients with diagnoses of breast cancer, non-Hodgkin's lymphoma, Hodgkin's disease, or multiple myeloma were prospectively randomized to one of the three treatment arms. All patients were treated with a chemotherapy (only) preparative regimen. The source of hematopoietic reconstitution was PBPC alone (without autologous marrow), and all patients yielded a minimum of 2 x 10(6) CD34+ cells per kilogram. Times to neutrophil engraftment and platelet engraftment were identical in the three treatment groups, with neutrophil engraftment occurring at a median of 10, 11 and 11 days when starting G-CSF on day 0, day 3 or day 5, respectively. Time to platelet transfusion independence was 14, 11 and 14 days by treatment group. We conclude that delaying the initiation of G-CSF from day 0 to day +5 does not affect engraftment and results in cost savings.

A randomized study of multi-day infusion of autologous peripheral blood progenitor cells.

Peripheral blood progenitor cells (PBPC) are increasingly used as the source of stem cells in both the autologous and allogeneic settings. Based on previous early non-randomized studies reporting enhanced engraftment following fractionated autologous PBPC infusion, some centers and study groups infuse PBPC over 3 days. To study the possible benefit of multiple day PBPC infusion, 60 patients receiving high-dose chemotherapy and autologous progenitor cell transplantation (ABMT) were randomized to receive their PBPC divided over 1, 2 or 3 days. Stem cells were mobilized with G-CSF 5 microg/kg for 7 days and PBPC were collected on days 5-7. Patients received daily G-CSF 5 microg/kg i.v. over 30 min beginning 4 h after the infusion of the first aliquot of PBPCs. Toxicity was similar for the 1, 2 and 3 day infusion groups. The median time to achieve 500 neutrophils/mm3 was 10, 11 and 11 days in the groups receiving PBPCs over 1, 2 or 3 days, respectively. The median time to achieve a platelet count of 20 x 10(9)/l was 11 days for the group receiving their cells as a single infusion and 12 days in the other two groups. We conclude that expanding PBPC infusion over 2 or 3 days does not enhance engraftment or reduce toxicity.

Progressive disease after ABMT for Hodgkin's disease.

A major limitation of ABMT for relapsed/refractory Hodgkin's disease is disease recurrence post-transplantation. We retrospectively reviewed 68 patients undergoing ABMT from January 1987 to June 1993. All received a uniform preparatory regimen (CBV). The median patient age was 30; 75% received prior radiation therapy and all patients received prior chemotherapy. Thirty-one percent presented at the time of transplantation with tumor masses larger than 10 cm. Sixty-two percent received autologous marrow alone and 38% PBPC with or without autologous bone marrow. Overall and progression-free survival are 43 and 36% at 5 years. Median follow-up for survivors is 59 months. Multivariate analysis revealed that tumor bulk was the most powerful poor prognostic factor for both survival and progression-free survival. Those transplanted with non-bulky tumors had an overall survival and progression-free survival of 52 and 44%, respectively, compared to those transplanted with bulky tumors who had an overall survival and progression-free survival of 22 and 16% (P = 0.03 and P = 0.04, respectively). Twenty-seven patients have relapsed. Four relapsed more than 2 years after ABMT. Four of the 27 patients who have relapsed remain alive, two without evidence of disease. The time after transplant to relapse was prognostically important, with no patients who relapsed within 6 months of ABMT still being alive, compared with 25% of patients who relapsed 7 or more months after ABMT who are still alive. We conclude that salvage therapy for relapse after ABMT is appropriate, as some patients may achieve prolonged survival. The time from transplant to relapse is an important survival predictor.

High-dose chemotherapy with autologous peripheral blood progenitor cell support for primary breast cancer in patients with 4-9 involved axillary lymph nodes.

Breast cancer patients with more than three involved axillary lymph have a high likelihood of relapse after adjuvant therapy. Early results of administration of high-dose chemotherapy (HDCT) and autologous peripheral blood progenitor cells (PBPC) to patients with primary breast cancer and > or = 10 involved axillary nodes have been encouraging. We performed a multicenter trial to determine whether HDCT could be safely administered to patients with primary breast cancer involving 4-9 axillary lymph nodes. Fifty-four patients with stage II or III breast cancer and 4-9 involved axillary lymph nodes received doxorubicin-based induction chemotherapy, followed by high-dose cyclophosphamide (5.625 g/m2), cisplatin (165 mg/m2), and BCNU (450 mg/m2) and PBPC mobilized by sargramostim (GM-CSF) or filgrastim (G-CSF). After completion of HDCT, patients received radiation therapy to the chest wall or involved breast, plus tamoxifen. Survival and disease-free survival, time to engraftment, and charges associated with HDCT were determined. Plasma concentrations of BCNU were determined and plasma AUC(BCNU) was calculated. Fifty-four patients were evaluable for survival and relapse-free survival. Fifty-two patients received HDCT with PBPC support and were evaluable for toxicity. Fifteen patients (29%) developed late pulmonary drug toxicity, which resolved with a 10-week course of corticosteroids in all but one affected patient, who subsequently died of pulmonary toxicity. Ten patients relapsed a median of 426 days (range 86-1117 days) after the start of induction chemotherapy, seven of whom have died. Forty-three patients are alive and breast cancer-free at a median of 947 days (range 661-1730 days) after the start of therapy, including one patient who developed myelodysplastic syndrome 809 days after the start of HDCT. Actuarial 4-year survival and disease-free survival from the start of treatment are 84 and 71%, respectively. Mean plasma AUC(BCNU) was 400 (range 82-1255) microgxmin/ml and was not statistically different from that measured in historical controls who received 600 mg/m2 of BCNU. Combined hospital and physician charges for patients treated at the University of Colorado decreased from a mean of $125845 for the first four patients to $77126 for the final seven patients. We conclude that HDCT with autologous PBPC can be administered with acceptable safety to patients with primary breast cancer involving 4-9 axillary lymph nodes. An ongoing, prospective randomized trial is evaluating the efficacy of HDCT for this patient group.

Continuous-infusion granisetron compared to ondansetron for the prevention of nausea and vomiting after high-dose chemotherapy.

PURPOSE: The serotonin receptor antagonists effectively prevent emesis with little toxicity when employed with standard doses of emetogenic chemotherapy. The optimal approach to the prevention of the emesis associated with the high doses of chemotherapy used for autologous stem cell transplantation is not known. A randomized controlled trial was designed to assess the relative efficacy and toxicity of granisetron compared to ondansetron in the setting of autologous stem cell transplantation. METHODS: A group of 48 patients with breast cancer were randomized in a double-blind fashion to receive either (1) granisetron as a 0.5-mg i.v. bolus 30 min. before chemotherapy followed by a continuous infusion of 0.04 mg/h (1 mg/day) for 7 days or (2) ondansetron as an 8-mg i.v. bolus 30 min before chemotherapy followed by a continuous infusion of 1 mg/h (24 mg/day) for 7 days. All patients also received 10 mg dexamethasone/day i.v. for 7 days. Chemotherapy consisted of 1500 mg cyclophosphamide per m2/day, 125 mg thiotepa m(-2) day(-1), and 200 mg carboplatin per m2/day all as a continuous infusion for 4 consecutive days. The two study arms were then compared for the incidence and severity of nausea, incidence of emesis, number of salvage anti-emetics required, cost, and toxicity. RESULTS: A total of 46 patients were evaluable. The treatment arms were well-balanced for known risk factors for chemotherapy-induced nausea and vomiting. Compliance with self-reporting of nausea and vomiting was poor but indicated no difference between the two treatment arms. The average number of anti-emetics required was 15.8 in both treatment arms and the average time to the first dose of a salvage anti-emetic was 2.8 days in the granisetron arm and 2.9 days in the ondansetron arm. The incidence of headache was 36 % in the granisetron arm and 39 % in the ondansetron arm. None of these differences was statistically significant. The use of granisetron resulted in a cost saving of 6.5 %. CONCLUSION: There was no significant difference between granisetron and ondansetron in either efficacy or toxicity. At our institution, the use of granisetron resulted in a moderate cost saving.

Breast cancer screening.

Breast cancer is the most common malignancy among women in the United States; however, recent data demonstrates a decline in the mortality rate, which may be attributed to early detection from screening programs combined with effective therapies for early stage disease. As a result of the prevalence of breast cancer and its association with highly emotional issues, screening recommendations have aroused debate in the scientific, public, and legislative domains. A general consensus supports breast cancer screening among women between the ages of 50 and 70; however, much controversy exists regarding screening for women age 40 to 49 or above age 70. This article explores the issues involved in determining breast cancer screening recommendations among asymptomatic women with average risk in the United States.

The effects of gonadotropins on metabolism of isolated rat granulosa cells.

FSH in vitro, but not LH, increased the O2 uptake of isolated granulosa cells from 23 day old rats previously treated with DES or with DES and FSH. Dose response studies showed that the cells were most sensitive to FSH when the cellular binding of FSH was highest. LH increased the O2 uptake of granulosa cells of untreated 30 day old rats. DES treatment inhibited the LH induced rise in O2 uptake when the rats were implanted with DES capsules unless FSH was injected to induce LH receptors. Addition of dbcAMP in vitro increased O2 uptake of granulosa cells from 30 day old rats at concentrations 10X lower than those required to stimulate O2 uptake in cells from 23 day old rats treated with DES alone.