Pegylated liposomal doxorubicin plus cyclophosphamide followed by paclitaxel as primary chemotherapy in elderly or cardiotoxicity-prone patients with high-risk breast cancer: results of the phase II CAPRICE study.

Anthracycline and taxane-based primary chemotherapy (PCT) is the standard treatment for high-risk breast cancer (HRBC). However, conventional anthracyclines are not commonly used in elderly patients or those prone to cardiotoxicity. Pegylated liposomal doxorubicin, (PLD) has comparable efficacy, but less cardiotoxicity than conventional anthracyclines. We conducted a phase II single-arm trial to assess the efficacy and safety of PCT based on PLD followed by paclitaxel (PTX) in a HRBC population usually undertreated. Fifty patients with stage II-IIIB breast cancer and at least one risk factor for developing cardiotoxicity initiated PLD 35 mg/m(2) plus cyclophosphamide 600 mg/m(2) every 4 weeks for four cycles, followed by 80 mg/m(2) weekly PTX for 12. Close cardiac monitoring was performed. Primary endpoint was the pathological complete response rate (pCR) in the breast. Treatment delivery and toxicities were assessed. Eighty-four per cent of patients were older than 65 years, 64 % suffered from hypertension, and 10 % had prior cardiac disease. In an intention-to-treat analysis, breast pCR was 32 % (95 % CI 19.5-46.7 %) and pCR in breast and axilla was 24 % (95 % CI 12.1-35.8 %). At diagnosis only, 26 % of patients were candidates for breast conservative surgery, which increased to 58.7 % after PCT. No significant decrease in left ventricular ejection fraction was seen. PLD followed by PTX was feasible in a fragile population of patients who were not candidates for conventional doxorubicin. Moreover, it achieved a pCR similar to standard therapy and could therefore be an option for elderly patients or cardiotoxicity-prone who present HRBC.

Increased signalling of EGFR and IGF1R, and deregulation of PTEN/PI3K/Akt pathway are related with trastuzumab resistance in HER2 breast carcinomas.

BACKGROUND: Trastuzumab resistance hampers its well-known efficacy to control HER2-positive breast cancer. The involvement of PI3K/Akt pathway in this mechanism is still not definitively confirmed. METHODS: We selected 155 patients treated with trastuzumab after development of metastasis or as adjuvant/neoadjuvant therapy. We performed immunohistochemistry for HER2, ER/PR, epidermal growth factor 1-receptor (EGFR), α-insulin-like growth factor 1-receptor (IGF1R), phosphatase and tensin homologue (PTEN), p110α, pAkt, pBad, pmTOR, pMAPK, MUC1, Ki67, p53 and p27; mutational analysis of PIK3CA and PTEN, and PTEN promoter hypermethylation. RESULTS: We found 46% ER/PR-positive tumours, overexpression of EGFR (15%), α-IGF1R (25%), p110α (19%), pAkt (28%), pBad (22%), pmTOR (23%), pMAPK (24%), MUC1 (80%), PTEN loss (20%), and PTEN promoter hypermethylation (20%). PIK3CA and PTEN mutations were detected in 17% and 26% tumours, respectively. Patients receiving adjuvant trastuzumab with α-IGF1R or pBad overexpressing tumours presented shorter progression-free survival (PFS) (all P≤0.043). Also, p110α and mTOR overexpression, liver and brain relapses implied poor overall survival (OS) (all P≤0.041). In patients with metastatic disease, decreased PFS correlated with p110α expression (P=0.024), whereas for OS were the presence of vascular invasion and EGFR expression (P≤0.019; Cox analysis). CONCLUSION: Our results support that trastuzumab resistance mechanisms are related with deregulation of PTEN/PI3K/Akt/mTOR pathway, and/or EGFR and IGF1R overexpression in a subset of HER2-positive breast carcinomas.

Prescription refill, patient self-report and physician report in assessing adherence to oral endocrine therapy in early breast cancer patients: a retrospective cohort study in Catalonia, Spain.

AIMS: To compare different methods in order to assess adherence and persistence with oral endocrine therapy in women diagnosed with breast cancer (BC) in Catalonia. MATERIALS AND METHODS: This study covered all women newly diagnosed with stage I, II or IIIa BC and positive hormone receptors at six hospitals in Catalonia (Spain) in 2004. Adherence was assessed on the basis of physician report and patient self-report using a telephone questionnaire. Persistence was measured by refill prescriptions. We used the Kappa index to compare adherence measures and logistic regression to evaluate adherence-related risk factors. RESULTS: The study covered a total of 692 women. Adherence ranged from 92% (self-report) to 94.7% (physician report), depending on the measure used; persistence was 74.7% at 5 years of follow-up. Low concordance between measures was observed (Kappa range: 0.018-0.267). Patients aged 50-74 years showed higher adherence than those aged <50 years. Adherence was also associated with: adjuvant chemotherapy and sequential hormonal therapy. CONCLUSIONS: Concordance between the different measures was remarkably low, indicating the need for further research. Adherence is an issue in the management of BC patients taking oral drugs, and should be assessed in clinical practice.

Socio-academic Factors Influencing Knowledge About Organ Donation among Medical Students in Paraguay, 2018.

Organ donation currently is an extremely important issue in public health. Proper information about the details of this topic is extremely important, but is not yet widespread among the public. This study was carried out with the aim to determine the level of knowledge about organ donation among medical students in Paraguay and associated socio-academic factors influencing their level of knowledge. This was an analytical cross-sectional study, based on a multicenter survey among university medical students. About 68.7% (235) of the respondents were preclinical students doing basic sciences. Two aspects were evaluated, the knowledge regarding the donation of the organs and the socio-academic factors, then both the aspects were evaluated through bivariate and multivariate analyses. There were 342 respondents with a median age of 22 years (interquartile range: 20-23 years) of which 263 (77%) were women. One hundred and eighty-eight (55%) reported not knowing the law that protects and regulates the activities of organ and tissue donation in Paraguay. In the multivariate analysis, the highest frequency of a good level of knowledge of organ donation occurred in those who were older [RPA: 1.07, 95% confidence interval (CI): 1.02-1.12, P = 0.007] and in two of the universities evaluated (both with values P <0.012). On the contrary, those who were preclinical students, in general, had a lower level of knowledge of organ donation (RPa: 0.61, 95% CI: 0.46-0.79; value P <0.001). Our findings denote relatively a poor knowledge of organ donation in some socio-academic subsets. Therefore, it is important to develop strategies to increase the knowledge about the subject, by creating opportunities by way of discussions and debates among the students at all academic levels and also by conducting academic conferences on the subject.

Gemcitabine and capecitabine in previously anthracycline-treated metastatic breast cancer: a multicenter phase II study (SOLTI 0301 trial).

BACKGROUND: On the basis of clinical activity of capecitabine and gemcitabine for metastatic breast cancer, we carried out a multicenter phase II clinical trial on the combination of these two agents in advanced anthracycline-pretreated breast cancer patients. Main objectives were to assess its efficacy and safety profile. PATIENTS AND METHODS: Seventy-six anthracycline-pretreated breast cancer patients were evaluated and were stratified according to previous treatment of advanced disease (group-1: not previously treated and group-2: previously treated). Study treatment consisted of gemcitabine 1000 mg/m(2), i.v., as 30 min-infusion, days 1 and 8 every 21 days, plus oral capecitabine 830 mg/m(2) b.i.d., days 1-14 every 21 days. RESULTS: Overall response rate was 61% for group-1, 48.5% for group-2 and 55.2% for the whole population. Clinical benefit rate was 73% for group-1, 80% for patients in group-2 and 76% for all patients. Median time to progression was 13.0 months for group-1, 8.2 months for group-2 and 11.1 months for the whole population. Most frequent grade 3-4 observed toxic effects per patient were neutropenia (60%), asymptomatic liver toxicity (13.5%), asthenia (14%) and hand-foot syndrome (16%). Only one patient presented febrile neutropenia. No treatment-related deaths occurred. CONCLUSION: Combination of gemcitabine and capecitabine is an active and safe regimen in anthracycline-pretreated breast cancer patients.

BOMET-QoL-10 questionnaire for breast cancer patients with bone metastasis: the prospective MABOMET GEICAM study.

BACKGROUND: Bone metastasis (BM) is the most common site of disease in metastatic breast cancer (MBC) patients. BM impacts health-related quality of life (HRQoL). We tested prospectively the psychometric properties of the Bone Metastasis Quality of Life (BOMET-QoL-10) measure on MBC patients with BM. METHODS: Patients completed the BOMET-QoL-10 questionnaire, the Visual Analogue Scale (VAS) for pain, and a self-perceived health status item at baseline and at follow-up visits. We performed psychometric tests and calculated the effect size of specific BM treatment on patients´ HRQoL. RESULTS: Almost 70% of the 172 patients reported symptoms, 23.3% experienced irruptive pain, and over half were receiving chemotherapy. BOMET-QoL-10 proved to be a quick assessment tool performing well in readability and completion time (about 10 min) with 0-1.2% of missing/invalid data. Although BOMET-QoL-10 scores remained fairly stable during study visits, differences were observed for patient subgroups (e.g., with or without skeletal-related events or adverse effects). Scores were significantly correlated with physician-reported patient status, patient-reported pain, symptoms, and perceived health status. BOMET-QoL-10 scores also varied prospectively according to changes in pain intensity. CONCLUSIONS: BOMET-QoL-10 performed well as a brief, easy-to-administer, useful, and sensitive HRQoL measure for potential use for clinical practice with MBC patients. TRIAL REGISTRATION: NCT03847220. Retrospectively registered on clinicaltrials.gov (February the 20th 2019).

Understanding the different relationships between mood and sleep disorders in several groups of non-oncological patients with chronic pain.

OBJECTIVE: To compare sleep dimensions in patients suffering from chronic pain of different origins, and with a group of pain-free subjects. To analyze the relationship between depression and/or anxiety and sleep disorders in musculoskeletal, neuropathic, and fibromyalgia patients. METHODS: This cross-sectional study included patients diagnosed with neuropathic pain (NP) (n = 104), musculoskeletal pain (MSK) (n = 99), or fibromyalgia (FM) (n = 51), and pain free subjects (n = 72). Information about sleep dimensions (MOS-sleep), duration and intensity of pain (Visual Analog Scale), and anxiety and depression (Hospital Anxiety and Depression scale) was collected. RESULTS: Of the 254 patients with chronic pain (PCP) studied, the mean pain intensity was 6.6 (SD = 1.9), with an average duration of 9 years. The scores in all sleep dimensions of the MOS-sleep were higher in CPP (more disturbances) compared to pain free patients, and differences were observed among the three groups of PCP, with FM most severely affected. Anxiety (ß = 1.3), depression (ß = 1.1), intensity (ß = 1.7), and duration of pain (ß = 0.04) were associated with more sleep problems in MSK patients. In contrast, anxiety (ß = 2.5) and duration of pain (ß = 0.05) were negatively related to sleep in the NP patients, and only depression (ß = 1.3) affected FM patients. CONCLUSIONS: The sleep pattern differs among groups of PCP in the presence or absence of mood disorders. Understanding these disorders in each specific group of PCP is fundamental, and it can contribute to improve the clinical situation of the patients and better orientating therapeutic strategies.

Update in the management of ovarian and cervical carcinoma.

Ovarian and cervical cancers are significant health problems. This article provides an update in selected management topics. Paclitaxel and platinum derivatives are the first-line treatment for patients with advanced disease. In selected patients, intraperitoneal chemotherapy has been associated with improved survival but the broad applicability of this strategy is limited by issues of toxicity and feasibility. Management of patients with recurrent disease is based on a number of factors and includes surgery in selected cases, platinum-based chemotherapy for patients with platinum-sensitive disease and other agents such as topotecan and pegylated liposomal formulation of doxorubicin for patients with platinum-resistant disease. In cervical cancer, the most significant issue/event is the demonstration of superior survival with topotecan and cisplatin compared to cisplatin alone. Finally, new agents such as epidermal growth factor receptor inhibitors and antiangiogenic agents are being currently tested in these settings.

[Renal function and cardiovascular risk in patients with essential hypertension. The "FRESHA" study]. / Función renal y riesgo cardiovascular en pacientes con hipertensión arterial esencial. Estudio FRESHA.

BACKGROUND: In the past few years there has been a growing amount of information about renal dysfunction and cardiovascular risk. The objectives of this study were to assess the prevalence of renal dysfunction and evaluate the relation between renal function and cardiovascular risk in patients with essential hypertension. METHODS: A multicenter, cross-sectional survey of unselected patients with essential hypertension attending primary care settings in Spain was performed between june and november 2004. Renal function was evaluated with the abbreviated equation of the Modification of Diet in Renal Disease study. Renal insufficiency was defined as an estimated glomerular filtration rate <60 ml/min/1.73 m2. RESULTS: Eighty-eight investigators from 50 centers recruited 2130 patients being mean age 65.6 +/- 11 years and female 53%. Prevalence of diabetes, lipid abnormalities, and previous cardiovascular disease were 30.3%, 45.9%, and 42.1% respectively. Prevalence of renal insufficiency was 32.4% (95% CI 30.4-34.4). Patients suffering from renal insufficiency showed a higher prevalence of cardiovascular disease when comparing with those with an estimated glomerular filtration rate = or >60 ml/min/1.73 m2 (56.2% vs. 35.3%, OR 2.35, 95% CI 1.95-2.82, p < 0.001). A logistic regression analysis showed that the relation of renal dysfunction with cardiovascular disease was independent of other variables or classical cardiovascular risk factors as age, female sex, diabetes, smoking, hypercholesterolemia, and systolic blood pressure. CONCLUSIONS: Renal insufficiency was present in 32.4% of patients with essential hypertension attending primary care settings. Cases with renal dysfunction showed a higher cardiovascular risk. Hypertensive patients with renal insufficiency should be considered as candidates for an aggressive approach of cardiovascular risk management.

Biweekly gemcitabine plus vinorelbine in first-line metastatic breast cancer: efficacy and correlation with HER2 extracellular domain.

Purpose. To assess the toxicity and efficacy of biweekly gemcitabine plus vinorelbine in first-line advanced breast cancer, and to establish whether circulating HER2 ECD levels correlate with the efficacy of the combination. Patients and methods. 52 patients were treated with gemcitabine 2500 mg/m(2) plus vinorelbine 30 mg/m(2), both on day 1 of 14-day cycles, for a maximum of 10 cycles. Baseline serum levels of HER2 ECD were assessed with an ELISA. Results. All patients were evaluable for toxicity, and 50 for efficacy. Overall toxicity was moderate. Grade 3 neutropenia occurred in 35% of patients and grade 4 in 19%. Other grade 3 toxicities were observed in less than 6%. There was one episode of febrile neutropenia, and one death after cycle three. Overall response rate was 52% (95% CI: 38% to 66%), with 2 patients achieving a CR (4%). Response rate did not correlate with HER2 ECD, with 50% of HER2 ECD positive patients responding, vs 48.5% of the HER2 ECD negative. Median overall survival was 24.6 months. Conclusion. Gemcitabine plus vinorelbine, given as an every-two-week schedule, is an active regimen in advanced breast carcinoma. This combination can be an option when anthracyclines and taxanes are not preferred. HER2 ECD has no predictive value in this non-taxane combination.

Assessing the Construct Validity and Internal Reliability of the Screening Tool Test Your Memory in Patients with Chronic Pain.

Patients with chronic pain often complain about cognitive difficulties, and since these symptoms represent an additional source of suffering and distress, evaluating the cognitive status of these patients with valid and reliable tests should be an important part of their overall assessment. Although cognitive impairment is a critical characteristic of pain, there is no specific measure designed to detect these effects in this population. The objective was to analyze the psychometric properties of the "Test Your Memory" (TYM) test in patients with chronic pain of three different origins. A cross-sectional study was carried out on 72 subjects free of pain and 254 patients suffering from different types of chronic pain: neuropathic pain (104), musculoskeletal pain (99) and fibromyalgia (51). The construct validity of the TYM was assessed using the Mini-Mental State Examination (MMSE), Hospital Anxiety and Depression Scale (HADs), Index-9 from MOS-sleep, SF-12, and through the intensity (Visual Analogical Scale) and duration of pain. An exploratory factor analysis was also performed and internal reliability was assessed using Cronbach's alpha. After adjusting for potential confounders the TYM could distinguish between pain and pain-free patients, and it was correlated with the: MMSE (0.89, p<0.001); HAD-anxiety (-0.50, p<0.001) and HAD-depression scales (-0.52, p<0.001); MOS-sleep Index-9 (-0.49, p<0.001); and the physical (0.49, p < .001) and mental components (0.55, p < .001) of SF-12. The exploratory structure of the TYM showed an 8-factor solution that explained 53% of the variance, and Cronbach's alpha was 0.66. The TYM is a valid and reliable screening instrument to assess cognitive function in chronic pain patients that will be of particular value in clinical situations.

Myocyte cell damage after administration of doxorubicin or mitoxantrone in breast cancer patients assessed by indium 111 antimyosin monoclonal antibody studies.

PURPOSE: To compare myocyte cell damage induced by doxorubicin or mitoxantrone, we performed left ventricular ejection fraction (LVEF) measurements and indium 111 antimyosin antibody studies in a group of patients with advanced breast cancer who had been treated with these anthracycline derivatives. PATIENTS AND METHODS: We studied 35 patients eligible to receive chemotherapy including the anthracyclines: doxorubicin or mitoxantrone (cumulative dose of doxorubicin, 500 mg/m2; or mitoxantrone, 120 mg/m2). LVEF was measured before and after 10 cycles of chemotherapy. Antimyosin uptake in the myocardium was quantified by means of a heart-to-lung ratio (HLR). RESULTS: Patients treated with doxorubicin presented with a significant decrease in LVEF after chemotherapy (before, 60.4% +/- 8.92%; after, 49.8% +/- 9.71%; P = .001). Antimyosin uptake was observed in all patients with a HLR of 2.03 +/- 0.25. Seven of eight patients with a HLR greater than 2.03 had a greater than 10% decrease in LVEF. Patients treated with mitoxantrone did not present with a decrease in LVEF after chemotherapy (before, 55.4% +/- 6.25%; after, 55.8% +/- 7.25%; not significant). Antimyosin uptake was observed in 14 of 17 patients with a HLR of 1.77 +/- 0.18 (P < .05). CONCLUSION: 111In antimyosin monoclonal antibodies defect myocardial cell damage produced by doxorubicin and mitoxantrone. In patients with advanced breast cancer, cumulative doses of 120 mg/m2 of mitoxantrone produce less myocardial cell damage than cumulative doses of 500 mg/m2 of doxorubicin. 111In antimyosin uptake without decrease in LVEF after treatment with mitoxantrone indicates the presence of myocyte cell damage, but not to the extent necessary to deteriorate function. These results indicate that 111In antimyosin antibody studies are useful in the noninvasive comparative assessment of cardiotoxicity produced by different anthracycline derivatives.

Circulating HER2 extracellular domain and resistance to chemotherapy in advanced breast cancer.

To test the hypothesis of an association between HER2 and chemotherapy resistance, we performed a prospective assessment of the predictive value of the circulating HER2 extracellular domain (ECD) in patients with advanced breast carcinoma in the setting of a multicenter Phase II trial using paclitaxel and doxorubicin. Serum samples were collected from 58 patients with metastatic breast carcinoma before first-line chemotherapy for advanced disease, and the levels of circulating HER2 ECD were measured using an enzyme immunoassay. Immunohistochemistry with anti-HER2 monoclonal antibody CB11 was used to assess the overexpression of HER2 in the primary tumors. When 450 fmol/ml was used as a cutoff, 24 cases (41%) had elevated HER2 ECD levels. Elevated levels of circulating HER2 ECD were associated with the expression of HER2 in the primary tumor tissue and with the metastatic tumor burden (evaluated with the marker CA 15-3; P = 0.032 and P = 0.002, respectively) but not with variables such as menopausal status, stage at diagnosis, previous adjuvant therapy, or the number of metastatic sites. The levels of circulating HER2 ECD correlated inversely with the response to treatment. The probability of obtaining a complete response to chemotherapy was significantly lower (P = 0.021) in patients with elevated HER2 ECD levels (0%; 95% confidence interval, 0-13%) compared with patients with nonelevated HER2 (26%; 95% confidence interval, 12-45%). In addition, the duration of clinical response was significantly shorter in patients with elevated HER2 ECD, compared with the cases with nonelevated HER2 (7.5 versus 11 months; P = 0.035). In conclusion, elevated levels of circulating HER2 ECD in patients with metastatic breast cancer correlate with reduced efficacy of a paclitaxel-doxorubicin chemotherapy combination. We suggest that the poor response rate associated with HER2 expression in advanced breast cancer may not be reversed by aggressive chemotherapy alone.

Paclitaxel plus doxorubicin in metastatic breast cancer: preliminary analysis of cardiotoxicity.

This ongoing phase II trial was designed to determine the antitumor activity and cardiotoxicity of a combination of doxorubicin (50 mg/m2) and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (175 to 225 mg/m2 over 3 hours) as first-line chemotherapy for metastatic breast cancer. Of 76 patients entered so far, 57 who had received at least three courses of chemotherapy are assessable for efficacy and cardiac toxicity. A slight majority (57%) of the patients entered had prior adjuvant chemotherapy, including 33% with anthracycline-containing combinations. An objective response was achieved by 70% of patients, with 18% complete responders. The main noncardiac toxicities were alopecia, neutropenia, mucositis, and peripheral neuropathy. Overall, after a median cumulative doxorubicin dose of 350 mg/m2, the evolution of left ventricular ejection fraction (LVEF) values did not significantly decrease from baseline to the sixth course of therapy. However, LVEF values decreased significantly in eight patients (14%). The LVEF decreased by more than 14% over basal values in three patients, although the final determination was still above the lower limits of normal. The remaining five patients had LVEF decreases that fell below the lower limits of normal (33% to 48%). None of the patients developed clinically evident heart failure. Our results indicate that the combination of doxorubicin (50 mg/m2) plus paclitaxel (175 to 225 mg/m2) is effective and does not induce a clinically relevant cardiotoxicity.

Dose-escalated paclitaxel in 1-hour infusion with a fixed dose of cisplatin in previously untreated advanced ovarian cancer: a phase II trial of the Spanish Group for Ovarian Cancer.

This phase II trial was planned to study the efficacy and toxicity of a fixed dose of cisplatin plus paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given over 1 hour with intrapatient dose escalation. Patients with advanced epithelial ovarian cancer (stages IIB-IV); Eastern Cooperative Oncology Group performance status < or = 2; normal renal, liver, and bone marrow function; and evaluable residual disease after debulking surgery were accrued. Paclitaxel was given over 1-hour infusion and dose was escalated from 175 to 200 and 225 mg/m2 if nadir neutrophil counts were > or = 1000/microL, platelets were > or = 100,000/microL, and neurotoxicity was less than grade 2. Cisplatin was given after paclitaxel at a fixed dose of 80 mg/m2. Six courses at 3-week intervals were planned. From May 1995 to August 1996, 68 patients were entered. Paclitaxel could not be escalated in six patients, another six received up to 200 mg/m2, and 45 received 225 mg/m2. Three hundred seventy-five courses were given: 27.7% at 175 mg/m2, 19.2% at 200 mg/m2, and 53.1% at 225 mg/m2. All patients were evaluable for toxicity, and 67 were evaluable for response. Thirty-five patients had a complete clinical response (51.4%), 20 had a partial response (29.4%), six had stable disease (8.9%), and six progressed on therapy (8.9%). Overall response rate was 80.8 (95% confidence interval, 71.3% to 90.1%). Second-look laparotomy was performed in 32 patients, and 20 of them (62.5%) had a pathologic complete remission. Grade 3 or 4 neutropenia was seen in 26 patients (38%), but only one had fever. Severe thrombocytopenia was not seen. Peripheral neurotoxicity (grade 1, 39.7%; grade 2, 42.6%; and grade 3, 8.8%) was dose-limiting. It is too early to report on time to progression and survival, and these data are not yet available. This combination of cisplatin with escalating doses of paclitaxel is feasible and very active, but the high incidence of peripheral neurotoxicity may limit its use.

Paclitaxel/gemcitabine administered every two weeks in advanced breast cancer: preliminary results of a phase II trial.

The purpose of this study was to evaluate the toxicity and efficacy of paclitaxel/gemcitabine administered every 2 weeks in the first-line treatment of advanced breast cancer. Forty-three chemonaive patients with histologically confirmed metastatic breast carcinoma were enrolled. Patients received paclitaxel 150 mg/m2 followed by gemcitabine 2,500 mg/m2, both on day I of a 14-day cycle, for a maximum of eight cycles. Thirty-four patients were evaluable for toxicity; 38 were evaluable for efficacy. The median age at the time of diagnosis was 54 years, the median performance status was 90, and the median number of lesions was three. Most patients (71%) had received prior adjuvant therapy. Grade 3 and 4 toxicity was limited to leukocytes (14% and 18%, respectively). Grade 3 toxicities (5% each) were thrombocytopenia, nausea and vomiting, elevation of aspartate transaminase, neurosensory, and constipation. One patient had neutropenia and fever. The objective response rate was 68% (21% complete response and 47% partial response); 18% had stable disease and 13% had partial disease. The preliminary evaluation of paclitaxel/gemcitabine given as a 2-week schedule to patients with untreated advanced breast carcinoma shows encouraging activity and a favorable toxicity profile.

Indium-111-antimyosin scintigraphy after doxorubicin therapy in patients with advanced breast cancer.

Indium-111-antimyosin (111In-antimyosin) scans were performed in 20 women with advanced breast cancer after 10 cycles of chemotherapy consisting of cyclophosphamide, 5-fluorouracil and doxorubicin (total cumulative dose of doxorubicin of 500 mg/m2). Antimyosin uptake in the myocardium was quantified by means of a heart-to-lung ratio (HLR). Antimyosin uptake in the myocardium was observed in 17/20 (85%) patients, and HLR after chemotherapy was 1.86 +/- 0.25. Left ventricular ejection fraction (EF) was determined before and after chemotherapy. Patients with decreased EF (8/20, 40%) presented with more intense antimyosin uptake (HLR of 2.11 +/- 0.10 versus 1.70 +/- 0.16 (p = 0.01]. HLR values correlated with EF values after chemotherapy (r = -0.47, p less than 0.05). Positive antimyosin studies after chemotherapy including doxorubicin, indicate the presence of myocardial damage in these patients. Antimyosin studies are a sensitive method to detect myocyte damage in patients after doxorubicin therapy.

Radioimmune imaging of bone marrow in patients with suspected bone metastases from primary breast cancer.

Radioimmune imaging of bone marrow was performed by technetium-99m- (99mTc) labeled antigranulocyte monoclonal antibody BW 250/183 (AGMoAb) scans in 32 patients with suspected bone metastases from primary breast cancer. AGMoAb scans showed bone marrow defects in 25/32 (78%) patients; bone invasion was subsequently confirmed in 23 (72%) patients. Conventional bone scans performed within the same week detected bone metastases in 17/32 (53%) patients (p less than 0.001). AGMoAb scans detected more sites indicating metastatic disease than bone scans in 12 of these 17 patients (71%). All patients with bone metastases in the axial skeleton had bone marrow defects at least at the sites of bone metastases. Of 15 patients with normal, or indicative of, benign disease bone scans, 8 patients (53%) presented with bone marrow defects in the AGMoAb scans. Bone invasion was confirmed in six of them. AGMoAb bone marrow scans provide a method for the early detection of bone metastatic invasion in patients with breast cancer and suspected bone metastases.

The role of granulocyte colony-stimulating factor (G-CSF) in the post-transplant period.

The administration of G-CSF post transplant has been shown to accelerate the time to neutrophil engraftment. However, this does not necessarily translate into a meaningful clinical benefit to the patient. This randomized study was designed to determine the role of G-CSF following transplantation in patients with breast cancer (BC). A total of 241 evaluable patients with BC were included. There were 200 patients with high-risk BC, and 41 had disseminated BC in complete remission. All patients received conventional dose chemotherapy prior to transplantation. Patients were mobilized with G-CSF, received the STAMP V regimen, were transplanted with > or = 2.5 x 10(6) of CD34(+) cells/kg and were then randomized to receive 5 microg/kg of G-CSF starting on the day of infusion (arm A), five days later (arm B), or no G-CSF (arm C). The need for transfusion support, infectious complications and length of hospitalization were the variables chosen to demonstrate clinical benefit. Patients receiving G-CSF reached 500 and 1000 neutrophils significantly faster (P = 0.001) than patients with no G-CSF. This translated into a significantly (P < 0.05) shorter hospitalization time for patients receiving G-CSF. Arm C was closed and, after recruiting 110 patients in arm A, and 106 in arm B, the significant difference in neutrophil recovery persisted with no difference in the time of hospitalization between arms A and B. Therefore, G-CSF significantly accelerates the time to neutrophil engraftment. This translates into a shorter time of hospitalization. There is no difference in this variable regarding the time of administering the G-CSF: day 0 vs day +5. Therefore, G-CSF on day +5 should be the standard in this setting.