The aim of this study is to evaluate the neuroprotective effect of antioxidant supplementation with vitamin E in patients treated with cisplatin chemotherapy.
Between April 1999 and October 2000, ...forty-seven patients were randomly assigned to either group one, which received vitamin E supplementation during cisplatin chemotherapy, or to group two, which received cisplatin chemotherapy alone. Alpha-tocopherol (vitamin E; 300 mg/d) was administered orally before cisplatin chemotherapy and continued for 3 months after the suspension of treatment. For preclinical studies, nude mice carrying the human melanoma tumor were treated with cisplatin alone or in combination with vitamin E.
Twenty-seven patients completed six cycles of cisplatin chemotherapy: 13 patients in group one and 14 patients in group two. The incidence of neurotoxicity was significantly lower in group one (30.7%) than it was in group two (85.7%; P <.01). The severity of neurotoxicity, measured with a comprehensive neurotoxicity score based on clinical and neurophysiological parameters, was significantly lower in patients who were supplemented with vitamin E than in patients who were not supplemented with vitamin E (2 v 4.7, P <.01). The results of the preclinical studies showed that when cisplatin was combined with vitamin E, no differences were observed in tumor weight inhibition, tumor growth delay, or life span as compared with treatment with cisplatin alone.
Supplementation of patients receiving cisplatin chemotherapy with vitamin E decreases the incidence and severity of peripheral neurotoxicity.
Angiogenesis, the process of generating new capillary blood vessels, is a fundamental requirement for normal physiological processes including embryogenesis, reproductive function and wound healing. ...Angiogenesis is also implicated in various pathological conditions including age-related retinal macular degeneration, diabetic retinopathy, rheumatoid arthritis, psoriasis and cancer growth and metastasis. Vascular endothelial growth factor (VEGF) is one of the best characterized of the pro-angiogenic growth factors, and multiple strategies have been developed to inhibit this pathway. Bevacizumab, a monoclonal antibody developed against VEGF, has shown initial preclinical and clinical activity. This review discusses the critical role of VEGF and summarizes the available data on the use of bevacizumab in colorectal cancer.
Intravenous bisphosphonates are the current standard of care for the treatment of hypercalcemia of malignancy and for the prevention of skeletal complications associated with bone metastases. ...Recently, retrospective case studies have reported an association between long-term bisphosphonate therapy and osteonecrosis of the jaws.
The data for twelve patients, referred to either an oral and maxillofacial surgeon or to an oral medicine specialist for the management of clinically apparent chronic oral osteonecrosis of unknown etiology, were reviewed. All had received cancer-related therapy simultaneously with bisphosphonate management.
The typical presenting symptoms were pain and exposed bone at the site of a previous tooth extraction. In most patients, the lesions initially occurred after dental extraction or other odontostomatological procedures, while five had a spontaneous event. Biopsy of the involved area showed the presence of necrotic lacunae, with infiltration of lymphocytes and histiocytes. In nine cases, there was histological or cytological diagnosis of suspicious osteomyelitis. No correlation was observed between the intraoral lesions and myelosuppression secondary to antineoplastic therapy.
Based on the patients' respective histories, clinical presentations and responses to surgical and antibiotic treatments, it appears that the pathogenesis of this osteonecrotic process is most consistent with localized vascular insufficiency. In our opinion, the mechanism by which bisphosphonates compromise bone vascularity may be related to their effect on the osteoclasts. The potent bisphosphonate-mediated inhibition of osteoclast function serves to decrease bone resorption and inhibit normal bone turnover remodeling, resulting in microdamage accumulation and a reduction in some mechanical properties of the bone.
The combination of anthracyclines and docetaxel have demonstrated a significant activity in metastatic breast cancer (MBC) as first-line chemotherapy. In a previous multicenter phase I study, we ...recommended two schedules of epirubicin-docetaxel combination for MBC: 1) epirubicin 75 mg/m2, docetaxel 80 mg/m2 every 3 weeks without G-CSF; 2) epirubicin 90 mg/m2 plus docetaxel 90 mg/m2 every 3 weeks, with G-CSF support.
Twenty-five advanced breast cancer patients were treated with epirubicin 90 mg/m2 plus docetaxel 90 mg/m2 every 3 weeks, with prophylactic G-CSF.
The main toxicity was grade 3-4 neutropenia (41% of cycles) despite the use of G-CSF; febrile neutropenia was observed in 14% of cycles necessitating a dose reduction of both drugs in 30% of patients. Response was observed in 79% of patients: 21% complete responses and 58% partial responses. The median response duration was 10 months (range: 3-16). The median time to progression was 11 months. The overall 3-year survival was 49.7%.
The antitumor activity observed in this series was comparable with that seen in other studies of taxane/anthracycline combinations. The degree of myelosuppression was severe, even though G-CSF was administered as a prophylactic. We recommend a lower dose of both drugs as reported by other authors.
This multicenter study describes the effectiveness of eribulin in current practice.
In total, 78 patients with advanced metastatic breast cancer, previously treated with two or more chemotherapy ...lines were enrolled.
The median duration of response and disease stability were 7.5 (5.4-9.5) and 8.9 (6.2-11.6) months, respectively, with a clinical benefit (CB) at 6 months in 41% of patients. CB in visceral and nonvisceral metastases were 72.7 and 88.9%, respectively. Eribulin was active also in brain metastases, with 47% CB. The activity was shown in all biological subtypes. Toxicities were manageable.
Our study confirms the effectiveness of eribulin mesylate in the treatment of patients with metastatic breast cancer and two or more lines of chemotherapy, in particular in the good disease control at the different metastatic sites.
To evaluate the efficacy of reduction of dexamethasone with a single-dose of palonosetron in preventing acute and delayed nausea and vomiting in patients receiving highly emetogenic chemotherapy ...(HEC) for early breast cancer.
Chemotherapy-naive patients with breast cancer were given HEC in an adjuvant or neoadjuvant setting. Palonosetron and dexamethasone 4 mg i.v. were given on day 1 and another two administrations of dexamethasone 4 mg i.m. were given on days 2 and 3. The end-point was complete response (CR) and complete control (CC) during the acute and delayed phases.
Twenty-six patients were observed. Complete response was achieved in 19 out of 26 patients (72.4%); the same result was shown in 72.4% out of 76 courses given.
This alternative schedule suggests efficacy for the control of acute and delayed emesis in moderately emetogenic chemotherapy. Further investigations are required to confirm these results.
Nausea and vomiting have a negative influence on the quality of life of patients receiving chemotherapy. The Consensus Conference held in 1997 outlined the therapeutic procedure to prevent delayed ...emesis that might otherwise be induced by chemotherapy. So far, no study has evaluated the correct management of delayed emesis in clinical practice. This study was performed in an attempt to verify the conformity of the delayed emesis therapy administered in some oncological centres with the Consensus Conference guidelines. A total of 149 patients were observed for a minimum of one up to a maximum of four chemotherapy cycles; analysis of the data took account of whether the chemotherapy had a high (HEC), moderate (MEC) or low (LEC) emetogenic potential. Among 42 patients who received HEC, 18 (43%) received antiemetic prophylaxis conforming to standards; 23 (54.7%) of these 42 had delayed emesis, only 8 (34.7%) of whom were treated with adequate antiemetic protection. MEC was administered to 72 patients, 46 (64%) of whom received adequate prophylaxis; delayed emesis was observed in 31 (43%) of the 72 patients, 20 (64.5%) of whom received antiemetic prophylaxis according to established guidelines. Of 35 patients treated with LEC, 22.8% manifested delayed emesis; a high percentage of these patients, 68.5%, received prophylaxis, even though it was unnecessary. Of all patients observed, only 50.3% received correct antiemetic protection. We deduce from the study that antiemetic treatment for delayed emesis in clinical practice needs more attention. Correct prophylaxis is necessary when HEC is given, and antiemetic protection for patients receiving MEC must be improved; among patients treated with LEC those at high risk must be identified so that overtreatment can be avoided.
The combination of paclitaxel and cisplatin is considered the standard regimen for advanced ovarian cancer (AOC). A meta-analysis has shown that the incorporation of anthracyclines into first-line ...chemotherapy might improve long-term survival by 7-10%. We designed a phase I-II study in patients with AOC using a combination of a fixed dose of cisplatin with paclitaxel and epirubicin both given at escalating doses every 3 weeks. The objectives of this study were to determine both the maximum tolerated dose (MTD) and the antitumor activity of this combination.
Six different dose levels were planned. The starting doses were cisplatin 75 mg/m2, paclitaxel 140 mg/m2, and epirubicin 50 mg/m2. The doses of paclitaxel were escalated in 20-mg/m2 increments, alternating with 20-mg/m2 increments of epirubicin. Ten patients with AOC entered the phase I study. Three patients each were enrolled at level I and level II and four patients at level III, and at each level, 15 courses were administered. Patients received a median of five courses.
Nonhematological toxicity was generally mild, except for grade 3 mucositis in one course at levels II and III, and grade 3 vomiting in one course at levels I and III. Hematological toxicities were grade 3-4 neutropenia in 60%, 47% and 60% of courses at levels I, II and III, respectively, and grade 3 anemia in one course at level III. At level III two of four patients developed a dose-limiting toxicity which was grade 4 neutropenia lasting more than 1 week.
The MTD was reached at level II with cisplatin 75 mg/m2, paclitaxel 160 mg/m2, and epirubicin 50 mg/m2. The phase II part of the study is currently ongoing.
