Showing papers by "Salomon M. Stemmer published in 2012"
TL;DR: In this combined analysis of three prospective trials, Osteonecrosis of the jaw was infrequent, management was mostly conservative, and healing occurred in over one-third of the patients.
633 citations
TL;DR: A systematic review and meta-analysis of randomized controlled trials demonstrating a beneficial effect to opioids in alleviating cancer-related dyspnea, and no advantage for the use of oxygen is demonstrated.
Abstract: Background. Dyspnea is commonly encountered by many cancer patients in the terminal stage of their disease and it severely hampers their quality of life. We aimed to evaluate the role of interventions to alleviate dyspnea. Methods. Systematic review and meta-analysis of randomized controlled trials assessing all interventions for dyspnea palliation in cancer patients, and searched the Cochrane Library, MEDLINE, conference proceedings, and references. Results. Our search yielded 18 trials. Eight studies evaluated opioids in any route of administration, seven studies evaluated the use of oxygen, two studies assessed the role of benzodiazepines and two studies evaluated the role of furosemide in alleviating cancer-related dyspnea. Weighted mean difference (WMD) was calculated for continuous variables that were reported on the same scale. For continuous data reported in different scales, standardized mean difference (SMD) was calculated. Meta-analysis of three trials yielded a positive effect for opio...
76 citations
TL;DR: A mechanism of chemotherapy-induced ovarian toxicity manifested by decreased ovarian blood flow accompanied by a reduction in ovarian size and diminished post-treatment AMH levels may imply a generalized phenomenon of end-organ toxicity.
Abstract: Background. Chemotherapy-related amenorrhea is a frequent side effect observed in young breast cancer patients. Studies in mice revealed that chemotherapy-induced gonadal toxicity may result from vascular damage. We prospectively evaluated ovarian blood flow and function in young breast cancer patients following chemotherapy. Methods. Young female patients with localized breast cancer undergoing adjuvant or neoadjuvant anthracycline- or taxane-based chemotherapy were evaluated using transvaginal ultrasound prior to initiation of and immediately after cessation of chemotherapy. Doppler-flow velocity indices of the ovarian vasculature—resistance index (RI), pulsatility index (PI)—and size measurements were
42 citations
TL;DR: Safety data from a randomised, phase III study evaluating first-line bevacizumab plus paclitaxel or capecitabine for locally recurrent or metastatic breast cancer is in-line with safety data reported in previous phase III trials.
19 citations
TL;DR: Two cases of posterior reversible leukoen-cephalopathy syndrome are described in two female patients that occurred a few days after receiving Cisplatin-based chemotherapy.
Abstract: Cisplatin is one of the most broadly used chemotherapeutic agents. Several central nervous system toxicities have been attributed to this agent, among which is a rare clinicoradiological condition referred to as posterior reversible leukoen-cephalopathy syndrome (PRES) or reversible posterior leukoencephalopathy syndrome (RPLS). PRES is characterized by subacute onset of headache, visual disturbances, confusion, seizures and rarely, coma. This usually reversible syn-drome was associated in the past mainly with hypertension. Several reports have associated the syndrome with several immunosuppressive and chemotherapeutic agents suggesting a disruption of the blood brain barrier due to direct damage to the endothelium and vasogenic edema. This syndrome is readily diagnosed with Computed Tomography (CT) or Magnetic resonance imaging (MRI) studies and quick withdrawal of the causative agent in conjunction with supportive care including rapid hypertension control and reduction of elevated intracranial pressure when needed, usually reverse the neurological symptoms with minimal or even no sequela within several days. In this brief report and review of the literature we describe two cases of PRES in two female patients that occurred a few days after receiving Cisplatin-based chemotherapy. We discuss the clinical presentation, diagnosis and treatment of this syndrome by reviewing the literature. The escalating number of clinical reports of PRES merit further studies of the mechanism of toxicity, appropriate treatment and awareness of physicians to this life threatening entity
10 citations
TL;DR: The non-inferiority criterion has not been met but OS results do not indicate relevant differences and secondary endpoints include response rate, progression-free survival, safety and quality of life.
9 citations
TL;DR: Extensive QoL evaluation in the TURANDOT trial revealed no clear difference in global health score and little or no difference in functioning and symptom scales between the treatment regimens, particularly in the first-line mBC setting, where clinically meaningful endpoints continue to be debated.
Abstract: Background: BEV has been shown to significantly improve the efficacy of both paclitaxel (PAC) and capecitabine (CAP) as first-line therapy for HER2-negative mBC. TURANDOT, a randomized phase III trial comparing BEV-PAC vs BEV-CAP, includes extensive QoL evaluation. Methods: Patients (pts) with HER2-negative mBC who had received no prior chemotherapy for mBC were randomized to receive either BEV-PAC (BEV 10 mg/kg d1 & 15 + PAC 90 mg/m2 d1, 8, & 15 q4w) or BEV-CAP (BEV 15 mg/kg d1 + CAP 1000 mg/m2 bid d1-14 q3w) until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint is overall survival (OS); QoL, assessed using the EORTC QLQ-C30, is a secondary endpoint. Pts were asked to complete QLQ-C30 at baseline, q12w during study therapy, at the end of treatment, and 28 days after discontinuing from the study. Results: On-treatment QoL questionnaires were available from all 561 of the treated pts at baseline, 394 at week 12, 266 at week 24, 186 at week 36, 129 at week 48, and 50 pts ranged from +1.5 to +2.6. In the BEV-CAP arm, mean baseline score was 56.0; the mean score remained above the baseline mean score until week 96. Mean change from baseline ranged from −3.9 at week 84 to +4.9 at week 96. Mean scores for most individual symptom scales were low (typically Conclusion: Extensive QoL evaluation in the TURANDOT trial revealed no clear difference in global health score and little or no difference in functioning and symptom scales between the treatment regimens. Importantly, BEV-containing therapy was not associated with a deterioration in global health score in either arm. This has important implications when considering the potential benefit of a treatment, particularly in the first-line mBC setting, where clinically meaningful endpoints continue to be debated. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-17-03.
4 citations
TL;DR: This proof of concept study is designed to substantiate the anti-metastatic properties of upamostat for patients appropriate for first line therapy for MBC and to assess the pharmacokinetics (PK) of up amostat and capecitabine when combined.
Abstract: Background: uPA and its inhibitor PAI-1 play a key role in tumor invasion, metastasis and tumor growth. High levels of uPA and PAI-1 in breast tumors are statistically significant prognostic factors of disease-free (DFS) and overall survival (OS), which were validated at the highest level of evidence, as well as predictors for benefit of adjuvant chemotherapy. WX-UK1 is an active site competitive inhibitor of uPA with an inhibition constant in the submicromolar range. WX-671 (upamostat) is an oral prodrug of WX-UK1. In preclinical animal tumor models, both WX-UK1 and WX-671 have been shown to reduce the growth rate of implanted tumors, to inhibit invasion, and reduce metastases. This current proof of concept study is designed to substantiate the anti-metastatic properties of upamostat for patients appropriate for first line therapy for MBC. Methods: Female patients aged >18, with HER2 negative MBC appropriate for first line monotherapy with capecitabine, with adequate performance status, organ function, bone marrow reserve without brain metastases were eligible. Patients were randomized in a double-blind fashion to receive upamostat (200mg orally daily for 21 days) plus capecitabine (1000 mg/m2 orally twice daily for 14 days) vs. capecitabine (1000 mg/m2 orally twice daily for 14 days) in 3 week treatment cycles until progressive disease or unacceptable toxicity. The primary endpoint is to evaluate the efficacy of the combination of upamostat plus capecitabine compared to monotherapy as assessed by comparison of progression free survival. The secondary objectives are OS, objective response rates, safety and tolerability, and to assess the pharmacokinetics (PK) of upamostat and capecitabine when combined. Results: Between August 2008 and April 2011,132 patients were enrolled. 17 patients are still receiving treatment. 26% of the patients are characterized as triple negative, 13% as only Estrogen Receptor (ER) positive and 4% as only Progesteron Receptor (PR) positive. 57 % of the patients are ER and PR positive. Conclusions: Progression free survival, response rates and safety will be reported. This abstract is being submitted as a placeholder. A completed abstract will be submitted when the analyses are completed. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-20-01.
3 citations
TL;DR: The TURANDOT trial as discussed by the authors compared paclitaxel (PAC) and capecitabine (CAP) with BEV until disease progression or unacceptable toxicity and showed non-inferior overall survival (OS) with PAC vs BEV-CAP.
3 citations
TL;DR: A systematic review and meta-analysis of all randomized controlled trials (RCTs) that evaluate the effects of BP treatment on survival in patients with early breast cancer in the adjuvant setting finds inconsistent evidence.
Abstract: 548 Background: The role of bisphosphonates (BP) in the adjuvant setting in breast cancer has been evaluated in several studies, yielding inconsistent evidence. We performed a systematic review and...
2 citations
TL;DR: A neoadjuvant regimen of doxorubicin with or without a sequential taxane, in which the number of cycles and the sequential administration of taxane are determined according to clinical response, appears to be safe and effective for patients with locally advanced breast cancer and yields a high rate of breast conservation.
Abstract: Background: Despite the growing number of clinical trials assessing preoperative systemic chemotherapy (PST) for locally advanced breast cancer, the optimal regimen has still to be defined. Purpose: This was to evaluate the toxicity, operability rate, pathological response rate and disease-free and overall survival associated with a PST regimen consisting of the sequential administration of single agents according to the individual tumor response. Methods: Medical files were reviewed of 102 consecutive patients with breast cancer treated in 2000–2007 with a neoadjuvant sequential regimen of doxorubicin followed by taxane. The number of cycles and the addition of taxane were based on tumor response. Results: Seventy percent of the patients had inoperable disease at diagnosis and 29% were given preoperative therapy for breast conservation. All patients underwent surgery, 65% achieved breast conservation. An overall pathological complete response (breast and nodes) was achieved in 14% of the patients, and a complete nodal pathologic response in 34%. At a median follow-up of 54 months, the overall survival rate was 82% and the disease-free survival rate was 70%. There was no treatment-related mortality. Febrile neutropenia occurred in 19% of the patients. Conclusions: A neoadjuvant regimen of doxorubicin with or without a sequential taxane, in which the number of cycles and the sequential administration of taxane are determined according to clinical response, appears to be safe and effective for patients with locally advanced breast cancer and yields a high rate of breast conservation. Tailored PST can spare patients receiving unnecessary chemotherapy.