Trials In Breast Cancer Patients Research Articles

Taxane-induced alopecia: A historical review of patients with ovarian or breast cancer treated with with paclitaxel, docetaxel or paclitaxel poliglumex

8044 Background: Data from ovarian cancer patients treated with platinum and either paclitaxel (P) or cyclophosphamide (CYC) show that alopecia is predictive of reduced quality of life (QOL). Paclitaxel poliglumex (PPX; XYOTAX) is a macromolecular drug conjugate linking paclitaxel with poly-L-glutamic acid, a biodegradable polymer. PPX is water soluble and administered as a 10-minute infusion without premedication. Preclinical and clinical findings show that PPX is relatively stable in plasma; over 95% of paclitaxel in circulation is present as the inactive conjugate. Reduced systemic exposure to high concentrations of free paclitaxel may result in a more favorable toxicity profile, including minimal alopecia. Methods: We compared rates and grades of P- or docetaxel-induced alopecia (reported in prescribing information [PI]) to PPX-induced alopecia (phase 1–2 clinical trials). Results: Pooled analysis of 10 studies of P showed that alopecia was observed in 87% of patients with ovarian (n = 493) or breast cancer (n = 319). Alopecia occurred in 74.2% of docetaxel-treated patients with breast cancer (n=965). In combination trials in previously untreated ovarian carcinoma, alopecia incidence (all grades/grade 3) was 96%/51% with P 175 mg/m2 plus cisplatin (C) 75 mg/m2 (n = 339), and 55%/6% with P 135 mg/m2 plus C 75 mg/m2 (n = 196). In a combination trial in breast cancer patients (n=744), alopecia incidence (all grades) was 97.8% with docetaxel 75 mg/m2 plus doxorubicin 50 mg/m2 and CYC 500 mg/m2. In contrast, grade ≥2 alopecia was absent in a phase 2 trial of PPX 175 mg/m2 in 99 heavily pretreated patients with recurrent ovarian cancer; hair thinning (grade 1) was reported in 7% of patients. No alopecia was reported in 17 patients with advanced breast cancer receiving PPX 235 mg/m2. Pooled analysis of phase 1–2 trials indicate that grade 3 alopecia (total hair loss) has not been observed in any patient treated with PPX (n = 275), including 47 patients receiving PPX plus C. Conclusions: PPX induces infrequent and mild alopecia compared with standard taxanes. Delivery of effective taxane therapy without the negative impact of hair loss on QOL is an important advantage for PPX. No significant financial relationships to disclose.

Laser (and LED) Therapy Is Phototherapy

Laser (and LED) Therapy Is Phototherapy

Comparison of pegfilgrastim vs. lenograstim in the treatment of chemotherapy-induced neutropenia in adult patients with acute myelogenous leukemia (AML)

6669 Background: Two phase III trials in breast cancer patients treated with myelosuppressive chemotherapy showed that a single dose of pegfilgrastim provides neutrophil support comparable with tha...

Comparison of pegfilgrastim vs. lenograstim in the treatment of chemotherapy-induced neutropenia in adult patients with acute myelogenous leukemia (AML)

6669 Background: Two phase III trials in breast cancer patients treated with myelosuppressive chemotherapy showed that a single dose of pegfilgrastim provides neutrophil support comparable with that provided by an average of 11 daily injections of filgrastim. In acute myelogenous leukemia (AML) data are sparse regarding the recovery of neutrophil counts (NC) after therapy with G-CSF in chemotherapy-induced neutropenia. We compared the effects of pegfilgrastim vs. lenograstim by these patients (pts). Methods: Retrospective analysis of unselected pts with AML, 18–75 yrs of age, ECOG ≤ 2, excluding pregnancy received at least one cycle of chemotherapy. On day 1 after chemotherapy treatment either pegfilgrastim 6 mg/once per cycle or lenograstim 5 micg/kg b.w. was administered. Primary objective was the time to recovery (TTR) of NC ≥ 1.0 G/L in each treatment group after injection of G-CSF if NC nadired < 1.0 G/L temporarily. Secondary objectives were the rate of transfusion of packed red blood (PRB) and pooled platelets (PLT). Results: 29 pts, 11 m + 18 f, aged median 61.4 yrs (range: 27–75) received 47 cycles. In 5 pts (3 pts in the pegfilgrastim and 2 pts in the lenograstim group) treatment failed to elevate NC ≥ 1.0 G/L. There was a difference in the TTR of NC between pegfilgrastim 11.1 ± 6.2 days (range: 6–28) and lenograstim 13.3 ± 3.6 days (range: 6–22). Detailed characteristics are summarized in table 1. Conclusions: Both G-CSF showed adequate recovery of NC with a faster increase in those patients where pegfilgrastim was administered. Less frequently blood products were transfused in the pegfilgrastim group. According to the whole-sale pharmacy prices in Germany, G-CSF treatment per cycle for a median of 13 vials of lenograstim was about € 2,321/US $ 2,785 (range: € 1,071–3,928/US $ 1,285–4,714) compared with 1 syringe of pegfilgrastim € 1,762/US $ 2,114. No significant financial relationships to disclose.

Regression modeling with recurrent events and time-dependent interval-censored marker data.

In life history studies involving patients with chronic diseases it is often of interest to study the relationship between a marker process and a more clinically relevant response process. This interest may arise from a desire to gain a better understanding of the underlying pathophysiology, a need to evaluate the utility of the marker as a potential surrogate outcome, or a plan to conduct inferences based on joint models. We consider data from a trial of breast cancer patients with bone metastases. In this setting, the marker process is a point process which records the onset times and cumulative number of bone lesions which reflects the extent of metastatic bone involvement The response is also a point process, which records the times patients experience skeletal complications resulting from these bone lesions. Interest lies in assessing how the development of new bone lesions affects the incidence of skeletal complications. By considering the marker as an internal time-dependent covariate in the point process model for skeletal complications we develop and apply methods which allow one to express the association via regression. A complicating feature of this study is that new bone lesions are only detected upon periodic radiographic examination, which makes the marker processes subject to interval-censoring. A modified EM algorithm is used to deal with this incomplete data problem.

Weight loss in breast cancer patient management.

To systematically review and summarize evidence relevant to obesity and breast cancer clinical outcome, potential hormonal mediating mechanisms, and the current status of weight loss interventions for chronic disease management. A comprehensive, formal literature review was conducted to identify 5,687 citations with key information from 159 references summarized in text and tables. This process included a search for all breast cancer studies exploring associations among survival or recurrence and obesity at diagnosis or weight gain after diagnosis using prospective criteria. On the basis of observational studies, women with breast cancer who are overweight or gain weight after diagnosis are found to be at greater risk for breast cancer recurrence and death compared with lighter women. Obesity is also associated with hormonal profiles likely to stimulate breast cancer growth. Recently, use of weight loss algorithms proven successful in other clinical settings that incorporate dietary therapy, physical activity, and ongoing behavior therapy have been endorsed by the National Institutes of Health and other health agencies. Although definitive weight loss intervention trials in breast cancer patients remain to be conducted, the current evidence relating increased body weight to adverse breast cancer outcome and the documented favorable effects of weight loss on clinical outcome in other comorbid conditions support consideration of programs for weight loss in breast cancer patients. Recommendations for the clinical care of overweight or obese breast cancer patients are offered.

The Role of Bisphosphonates in Breast Cancer Management: Review Article

SummaryBone metastases are a common problem in the management of breast cancer and are associated with considerable morbidity. Bone pain, hypercalcaemia, fractures and cord compression all occur requiring interventions such as analgesia, radiotherapy and surgery. Bisphosphonates are drugs that are active in the bone microenvironment. Their effects on osteoclasts are well described: they potently inhibit osteoclast mediated bone resorption by delaying the maturation of immature osteoclasts and by directly inducing osteoclast apoptosis. It has been known for some time that bisphosphonates, in combination with intravenous rehydration, effectively treat hypercalcaemia associated with solid malignancies. It has now been demonstrated in clinical trials in breast cancer patients that regular bisphosphonate administration reduces the morbidity associated with osteolytic skeletal metastases. There is an emerging suggestion from clinical trial work that bisphosphonates may be able to reduce or delay the development of skeletal metastases although this remains controversial as the three published trials present conflicting results. The more potent third-generation bisphosphonates, such as zoledronate, are now being tested for each of these indications with promising results and may replace other bisphosphonates in the future. Laboratory studies have recently demonstrated that bisphosphonates have direct cytotoxic effects against breast cancer cells in vitro, inducing apoptosis and preventing adhesion to bone. This adds support to the hypothesis that bisphosphonates may have a genuine beneficial effect in the adjuvant setting.

Pulmonary toxicity after radiotherapy in primary breast cancer patients: results from a randomized chemotherapy study

Purpose : Pulmonary toxicity was prospectively evaluated within a randomized trial for breast cancer patients at high risk for relapse, who postoperatively received as adjuvant therapy either 9 cycles of tailored chemotherapy (20 patients) (cyclophosphamide, epirubicin, 5-fluorouracil [FEC]) or standard FEC × 3 followed by high-dose chemotherapy (cyclophosphamide, thiotepa, carboplatin [CTCb]) supported by peripheral blood stem cell transplantation (14 patients). After high-dose chemotherapy or tailored FEC, all patients received locoregional radiotherapy (50 Gy/5 weeks), plus tamoxifen for 5 years. Methods and Materials : Lung function tests (FVC, FEV1, and DL CO) were performed before chemotherapy and 9 months after radiotherapy. Computed tomography of the lungs was performed before radiotherapy and 6 weeks, 3 months, and 9 months after radiotherapy. Results : Clinical signs of suspected pneumonitis were noted in 29% of patients, but only 1 patient needed symptomatic therapy. Radiologic changes were detected in 68% of patients, and they were most frequent at 3 months after radiotherapy. FVC decreased in both groups (tailored FEC: mean difference, −6.5%, p = 0.0005; CTCb: −2.0%, p = 0.21; tailored FEC vs. CTCb: −4.5%, p = 0.05). DL CO decreased significantly in both groups (tailored FEC: mean difference, −11.2%, p < 0.0001; CTCb: −5.6%, p = 0.02; tailored FEC vs. CTCb: −5.6%, p = 0.07). FEV1 decreased by 7.3% in patients treated with tailored FEC ( p < 0.0001) and by 2.5% in patients treated with CTCb ( p = 0.03) (tailored FEC vs. CTCb: 3.7%, p = 0.08). Conclusions : Changes in pulmonary function were thus detected in both groups, although to a greater extent in the tailored FEC group. The clinical significance of these findings should be balanced carefully against the improved, statistically significant relapse-free survival achieved with the tailored FEC regimen compared to high-dose CTCb + peripheral blood stem cell transplantation (PSCT).

Long-term prognosis of breast cancer patients with 10 or more positive lymph nodes treated with CMF

The purpose of this investigation was to study the long-term prognosis of breast cancer patients with 10 or more positive lymph nodes after conventional chemotherapy treatment with cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Between 1984 and 1989, 1048 node-positive patients were treated with CMF in two separate trials conducted by the German Breast Cancer Study Group (GBSG). Subgroups either received radiotherapy or tamoxifen in addition. In this study, long-term prognosis in the subgroup of 141 patients with 10 or more positive lymph nodes was investigated. Univariate and multivariate Cox models were used to evaluate the effect of prognostic factors on event-free survival (EFS) and overall survival (OS). Both univariate and multivariate analyses revealed the progesterone receptor (PR) status as the dominating prognostic factor for both EFS and OS, resulting in a strongly increased risk of more than 2-fold for receptor-negative patients. A large number of positive lymph nodes also affected the prognosis for EFS. In univariate analysis, the degree of lymph node involvement (i.e. percentage of positive nodes out of all examined nodes), oestrogen status (ER) status, and tumour grade also showed significant effects. To conclude, the prognosis in the subgroup of patients with 10 or more positive lymph nodes is heterogeneous. Some surprisingly high survival rates have been observed in case series of breast cancer patients treated with high-dose chemotherapy which may be explained by patient selection. From the usual factors investigated in this study, the PR status showed the strongest effect, and, at least this factor should be taken into account in the design and analysis of trials for breast cancer patients with a poor prognosis.

The psychotherapeutic value of a “Chat”: A verbal response modes study of a placebo attention control with breast cancer patients

In a randomized controlled trial of breast cancer patients awaiting surgery, 51 client-centered psychotherapeutic interventions and 56 “chats” were analyzed using Stiles' Verbal Response Modes (VRMs). The 30-minute interventions and chats were carried out the night before surgery by a consultant surgeon trained in client-centered counseling techniques. Significant differences in therapist and client VRMs were found between interventions and chats. Therapist reflection and acknowledgment were the predominant VRMs in the interventions. Significantly more therapist reflection and acknowledgment occurred in the interventions than in the chats, and were associated with significantly more client disclosure. However, intervention and chat patients were indistinguishable on most outcome measures. Some chats bore a resemblance to reminiscence therapy with the elderly. In a content analysis carried out on the chats, the most common topics were holidays, followed by family. Neither VRM disclosure, personal topics discussed, nor “significant” disclosures in the chats predicted better therapeutic outcome. However, themes of loss and symbolic restitution occurred in all 56 chat transcripts. It is hypothesized that the chats may have had psychotherapeutic value for patients as a form of “reminiscence therapy” and/or as an opportunity to explore symbolically issues of loss and restitution inherent in the life situation of waiting for breast surgery for cancer. The apparent psychotherapeutic value of a chat is discussed in the context of current perspectives on the equivalence paradox, and questions are raised regarding the design of adequate placebo attention control groups in psychotherapy research.