Adjuvant Chemotherapy For Breast Carcinoma Research Articles

A case of multiple cutaneous lesions due to Serratia marcescens in an immunocompromised patient

Introduction: Serratia marcescens is an opportunistic Gram-negative bacillus capable of causing serious nosocomial infection. Skin infections due to S. marcescens, although not frequently encountered, can have a variety of manifestations and may progress to become serious debilitating lesions if not diagnosed early and treated promptly. We report here a case of multiple skin lesions due to S. marcescens in an immunocompromised patient. Case presentation: A 60-year-old patient on adjuvant chemotherapy for breast carcinoma developed a high fever followed by multiple painful nodular and ulcerated lesions over all four limbs. Multidrug-resistant S. marcescens was isolated from the blood as well as from several skin lesions. Removal of the infective source (a chemoport in this case) and administration of tigecycline resulted in resolution of the infection. Conclusion: S. marcescens is a nosocomial pathogen capable of causing extensive cutaneous lesions. Multiple samples for culture from the lesions are recommended to identify the aetiological agent and institute appropriate antibiotics. The emergence of multidrug-resistant strains has compromised treatment options for this bacterium, which is intrinsically resistant to several groups of antibiotics.

P4-14-04: Tolerance of Docetaxel: Is Obesity a Risk Factor for Toxicity? A Pilot Study.

Abstract Background Few data are available in the literature regarding chemotherapy dosage adjustment in obese patients. Docetaxel is a lipophilic substance, highly bound to albumin; obesity might result in an accumulation of docetaxel and may lead to a higher rate of toxicity. The objective of this study was to assess the tolerance to docetaxel in obese and non obese patients, according to their body mass index (BMI). Methods A retrospective study was carried out. Patients were divided according to their BMI, considering a limit of 30 kg/m2. All patients received docetaxel (100 mg/m2) as a part of adjuvant chemotherapy for breast carcinoma. Toxicity of docetaxel such as neutropenia, hand-foot syndrome, mucositis, and neuropathy were assessed in both groups. Patients receiving concomitant therapies leading to similar adverse events were excluded (e.g. cyclophosphamide, 5-FU, …). The included patients received docetaxel alone or in association with trastuzumab or bevacizumab. Qualitative data analysis was performed using Fisher's exact test. Quantitative data were studied using the Student test. Results Among the 49 patients, 18 (37%) presented with a BMI > 30 kg/m2. The median age was 53 years-old in the group BMI > 30 and 55 years-old in the group BMI < 30 (p = 0.9383). The median dose intensity delivered was 91% (74-100%) in the group BMI> 30 and 97.7% (75-100%) in the group BMI < 30 (p = 0.06). The median value for albumin was 75 g/L (59-86 g/L) in the BMI > 30 and 71 g/L (56-79 g/L) in the BMI < 30 (p = 0.122). Toxicity in both groups was as follows: No neuropathy was observed in both groups. Conclusions Obese patients (BMI > 30 kg/m2) presented with more toxicities (p = 0.013). Hypoalbuminemia did not represent a risk factor for toxicity in this study as patients had normal albumin levels. Obesity is a risk factor for toxicity in patients treated with docetaxel. Dosage calculation according to body surface area is not suitable for these patients. Toxicity in the group BMI < 30 seems to demonstrate greater susceptibility to the molecule for these patients. Further studies will try to identify the different mechanisms of toxicity of docetaxel involved obese patients, including the interaction between docetaxel and fats. Measures have also to be taken to obtain a favorable effectiveness/toxicity balance in obese patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-14-04.

Relationship Between Thymidylate Synthase and p53 and Response to FEC Versus Taxane Adjuvant Chemotherapy for Breast Carcinoma

Many drugs can be used for adjuvant therapy of breast cancer, including anthracyclines, cyclophosphamide, 5-fluorouracil (5-FU) and, recently, taxanes (TXT)have shown promising results. 5-FU blocks thymidylate synthase (TS) which cross-links p53 mRNA, inhibiting its synthesis. TS overexpression is one of the main mechanisms involved in 5-FU drug resistance. Enough p53 mutations can confer resistance to chemotherapy using anthracyclines and 5-FU, while are associated with improved responses to TXT. The aim of this study was to examine the TS and p53 levels in tumor samples and to compare the efficacy of FEC (5-FU, epirubicin, cyclophosphamide) and TXT chemotherapy in a group of patients with differing TS and p53 status. We examined 84 breast tumor samples using immunohistochemistry. TS and p53 levels were inversely related, and TS and p53 positivity was significantly associated with the failure of FEC treatment and with a good response to TXT therapy (p <0.001). This confirms the predictive role of these two markers, which should be considered when choosing the appropriate adjuvant therapy for breast cancer.

Tolerance of docetaxel: Is obesity a risk factor for toxicity? A pilot study.

248 Background: Few data are available in the literature regarding chemotherapy dosage adjustment in obese patients. Docetaxel is a lipophilic substance, highly bound to albumin; obesity might result in an accumulation and may lead to a higher rate of toxicity. The objective of this study was to assess the tolerance to docetaxel in obese and non obese patients, according to their body mass index (BMI). Methods: A retrospective study was performed. Patients were divided according to their BMI, considering a limit of 30 kg/m2. All patients received docetaxel (100 mg/m2) as a part of adjuvant chemotherapy for breast carcinoma. Toxicity of docetaxel such as neutropenia, hand-foot syndrome (HFS), mucositis, and neuropathy were assessed in both groups. The included patients received docetaxel alone or in association with trastuzumab or bevacizumab. Qualitative data analysis was performed using Fisher's exact test. Quantitative data were studied using the Student test. Results: Among the 49 patients, 18 (37%) presented with a BMI greater than 30 kg/m2. The median age was 53 years in the group BMI greater than 30 and 55 years in the group BMI less than 30 (p = 0.9383). The median value for albumin was 75 g/L (59-86 g/L) in the BMI greater than 30 and 71 g/L (56-79 g/L) in the BMI less than 30 (p = 0.122). Toxicity in both groups is shown in the table below. No neuropathy was observed. Conclusions: Obese patients (BMI &gt; 30 kg/m2) presented with more toxicities (p = 0.013). Hypoalbuminemia did not represent a risk factor for toxicity in this study. Obesity is a risk factor for toxicity in patients treated with docetaxel. Dosage calculation according to body surface area is not suitable for these patients. Toxicity in the group BMI &lt; 30 seems to demonstrate greater susceptibility to the molecule for these patients. Further studies will try to identify the different mechanisms of toxicity of docetaxel involved obese patients, including the interaction between docetaxel and fats. Measures have also to be taken to obtain a favorable effectiveness/toxicity balance in obese patients. [Table: see text]

Analysis of the prognostic effects of inclusion in a clinical trial and of myelosuppression on survival after adjuvant chemotherapy for breast carcinoma

Analysis of the prognostic effects of inclusion in a clinical trial and of myelosuppression on survival after adjuvant chemotherapy for breast carcinoma

Analysis of the prognostic effects of inclusion in a clinical trial and of myelosuppression on survival after adjuvant chemotherapy for breast carcinoma

Treatment-related factors that might influence survival after adjuvant treatment for breast carcinoma include treatment as part of a clinical trial, toxicity of treatment, the regimen and schedule used, and dose intensity. The authors reviewed the records of 680 patients with breast carcinoma who received adjuvant treatment with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) at Princess Margaret Hospital between 1980-1990. They analyzed the effects on survival of inclusion in a clinical trial (n = 160) and of experiencing Grade 3/4 myelosuppression (according to National Cancer Institute Common Toxicity Criteria) (n = 227, with available data for 584 patients). In an exploratory analysis, the authors examined the effects of the CMF regimen ("classic" CMF [n = 417] vs. intravenous CMF [n = 243]) and of relative dose intensity. Each of these factors was tested in a Cox proportional hazards model with the known prognostic factors of N classification, T classification, estrogen receptor (ER) and progesterone receptor (PR) status, and use of adjuvant hormonal therapy to determine whether they provided additional prognostic information. In univariate analysis, inclusion in a clinical trial was associated with better survival (P = 0.02) with a nonsignificant trend when corrected for other prognostic factors in a multivariate analysis (hazard ratio [HR] = 0.77; 95% confidence interval [CI], 0.56-1.04). There was a similar trend for patients experiencing myelosuppression (HR = 0.77; 95% CI, 0.59-1.00). In exploratory analysis the use of classic CMF, with higher absolute dose intensity, also was associated with a trend toward improved survival (HR = 0.79; 95% CI, 0.63-1.00). The results of the current study suffer from the inherent problems of retrospective analysis, but, similar to findings for other disease sites, they suggest that patients included in clinical trials have better outcome. Classic CMF should be used when this regimen is selected for adjuvant treatment, and dose adjustment resulting in moderate myelosuppression should be explored in future clinical trials.

Changes in body composition during breast cancer chemotherapy with the CMF-regimen.

Weight gain is a reported problem associated with adjuvant chemotherapy for breast cancer and often generates psychosocial stress in women [1]. It also may affect prognosis and survival. Changes in body composition and weight during chemotherapy, particularly adjuvant treatment of breast carcinoma, have been previously reported [1-3]. Multiple reasons for this weight gain have been suggested though few theories have been scientifically validated [4]. The aim of this study was to investigate body composition and its relationship to weight change associated with the CMF-based breast cancer chemotherapy protocols. Total body nitrogen (TBN), body fat, total body water (TBW), and anthropometric measurements were conducted on 25 female out-patients (median age 47, range 26-70 years) receiving adjuvant CMF-based chemotherapy for breast cancer. Total body nitrogen was measured using the In Vivo Neutron Capture Analysis (IVNCA) technique (on day 1 of cycles 2-6) and TBP was calculated by multiplying TBN by 6.25 [5]. Nitrogen Index (NI) was calculated by expressing TBN as a percentage of normal. There was a significant increase in mean body weight during chemotherapy of 2.35 kg (p < 0.0001). Serial measurements showed no significant change in mean TBN, NI, or percentage body fat. Break down of body weight showed a significant increase in mean TBW of 0.79 kg (p = 0.003) and mean fat mass of 1.49 kg (p = 0.008). We conclude that weight gain observed during adjuvant chemotherapy for breast carcinoma is primarily due to an increase in fat and TBW.

73 Post-operative radiotherapy and concomitant adjuvant chemotherapy for breast carcinoma

Between May 1992 and December 1993, 72 patients operated for breast carcinoma underwent radiotherapy (RT) and concomitant adjuvant chemotherapy (CT). There were 2 T0, 23 T1, 47 T2 and 1 T4b. Lymph node status was 59 N0, 10 N1 and 4 unknown. Surgical treatment was lumpectomy (59) or mastectomy (13) and axillary dissection for all. Radiation therapy delivered 50 Gy in 5 weeks to the breast or chest wall. A 10 Gy boost was added to the tumor site after lympectomy. The internal mammary chain was irradiated in 64 patients, the subclavicular area in 53 and the axilla in I patient. The CT regimen was a combination of Mitoxantrone (12mg/m²), 5-FU (500 mg/m²) and Cyclophosphamide (500 mg/m²), 6 cycles were delivered with 21 days interval. Compliance to RT evaluated on dose and treatment length was good for 88%. On the 65 patients analysed for CT: 98% received all 6 cycles at the prescribed dose, but 69% strictly respected intercycle intervals. Mild digestive and cutaneous toxicity (grade 1 and 2) was observed in 50%. Major toxicity was neutropenia (grade 2 or 3) in 18 patients and 1 severe infection. The 3 year actuarial survival rate was 87%. No local relapse was observed Metastases occurred in 6 patients. These preliminary results show that this concomitant association is safe although compliance to chemotherapy should be improved.

Arterial thrombosis associated with adjuvant chemotherapy for breast carcinoma: A cancer and leukemia group B study

Multiagent chemotherapy and chemohormonal therapy for breast cancer are associated with an increased risk for venous thromboembolic complications. We observed instances of arterial thrombosis in two studies of breast cancer involving multiagent chemotherapy for stages II and III disease. Our purpose in this study was to determine the incidence of this complication and whether it appeared to be related to the chemotherapy or was a random event. Episodes of arterial thrombotic events were identified from record reviews of 1,014 assessable patients with breast cancer entered on two Cancer and Leukemia Group B protocols. Details of the kind of arterial event, when it occurred, the outcome, and the occurrence of metastases were analyzed. Thirteen (1.3%) patients had an arterial thrombosis: six (5.3%) of 113 patients with stage III disease and seven (0.8%) of 901 patients with stage II disease. Four of these patients had a peripheral arterial thrombosis and nine had strokes (four were fatal). All these events occurred while the patients were receiving adjuvant chemotherapy. Only one additional arterial event (a stroke approximately four years later) has occurred in this patient group after chemotherapy was completed. Arterial thrombosis is also associated with multiagent chemotherapy in patients with breast cancer. The mechanism is unknown.

Arterial thrombosis associated with adjuvant chemotherapy for breast carcinoma: A cancer and leukemia group B study☆☆☆

Arterial thrombosis associated with adjuvant chemotherapy for breast carcinoma: A cancer and leukemia group B study☆☆☆

Efficacy of bone and liver scanning in breast cancer patients treated with adjuvant chemotherapy.

One hundred nineteen patients who underwent mastectomy and received adjuvant chemotherapy for breast carcinoma were studied retrospectively. Of these, 102 patients had serial bone scans and 101 patients serial liver scans during a mean follow-up of 59 months. All had negative scans prior to chemotherapy. Twenty-three of 102 patients converted to positive bone scans during follow-up. These 23 patients converted a mean of 29.5 months after surgery. At conversion, 5 of 21 patients had bone pain, and none had elevated alkaline phosphatase. Thirteen of 101 patients developed positive liver scans a mean of 31.5 months after surgery. The liver scan was the first indicator of liver involvement in only 3 of 13 converters. In no case was the liver scan the first indication of metastatic disease. The incidence of bone scan conversion (22%) did not differ significantly from previously reported series of patients not receiving adjuvant therapy, but the mean time to conversion was prolonged (29.5 versus 18.0 months). In addition, none (0/21) of the bone scan converters had elevated alkaline phosphatase at the time of conversion. It is concluded that the interval from initial evaluation to bone scan conversion may be prolonged by adjuvant chemotherapy of breast cancer. It is recommended that patients have bone scans twice yearly for at least 3 to 4 years after surgery. This study emphasizes the singular importance of bone scanning in breast cancer patients who have adjuvant chemotherapy, as the scan may be the only indicator of bone involvement. Liver scans do not appear useful for screening patients without other evidence for metastatic liver involvement.

The Assessment of Nausea and Vomiting

Given the diversity of assessment methodologies in previous studies, and given the increasing attention being shown in studies in which nausea and vomiting are used as outcome measures, it is reasonable to expect that there are more questions on the assessment of nausea and emesis than there are answers. There is little consensus on the efficacy of various approaches used to help control chemotherapy-induced nausea and emesis. There is also little consensus on the appropriate assessment techniques for their measurement. While there is room for much controlled experimentation and study of the ways to assess nausea and emesis, a review of past studies indicates several guidelines that should be kept in mind. The first of these is that nausea is a subjective phenomenon. It exists only insofar as it is defined by the patient. The clinical reality is that patients' decisions to delay or terminate chemotherapy are based on their subjective evaluations of the side effects, not on evaluations made by a clinician or others. With this in mind, a self-report approach to the assessment of nausea appears the most reasonable at this time. On the other hand, while vomiting does have subjective aspects, it represents a behavior that may be reliably observed by others. Thus, it is appropriate that observer ratings be obtained whenever feasible. The use of such indirect measures of nausea and vomiting as time to food intake, appetite change, and other measures of patient well-being should be considered whenever feasible. As with all measures, the cost in patient time needs to be balanced against the scientific needs of any study quantifying nausea and vomiting. While direct, physiologic measures would provide an important external reference to the assessment of nausea and vomiting, at the present time, these appear useful only in animal studies. The fact that nausea and vomiting can occur independently points to the validity of their assessment as separate behaviors. It is also important to note that their frequency, severity, and duration are separable phenomena. A complete assessment of nausea and vomiting responses should include separate measures of frequency, severity, and duration. Anticipatory nausea and vomiting are clinical phenomena that appear to occur with a reasonable enough frequency so that their measurement would be important in clinical studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Extended surgical adjuvant chemotherapy for breast carcinoma

A preliminary report of a prospective study of adjuvant chemotherapy for breast carcinoma in patients with “high risk” breast cancer has been presented. Thio-TEPA was administered weekly in doses of 0.2 mg./kg. until leukopenia was observed. A significantly lower incidence of recurrent cancer has been observed in women receiving Thio-TEPA when compared with the control group. This difference appears to be more marked than that observed in the cooperative breast adjuvant study at a comparable point in time. A lower death rate has also been observed in the treated group.