Andrea Pace

Neuroprotective Effect of Vitamin E Supplementation in Patients Treated With Cisplatin Chemotherapy

Purpose: The aim of this study is to evaluate the neuroprotective effect of antioxidant supplementation with vitamin E in patients treated with cisplatin chemotherapy. Methods: 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. Results: 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 n...

α-tocopherol protects against cisplatin-induced toxicity without interfering with antitumor efficacy

Our aim was 2‐fold: to investigate the role of α‐tocopherol supplementation on the antitumor activity of DDP and to evaluate the effect of α‐tocopherol on the survival and neurotoxicity of DDP‐treated mice. Experiments performed on the M14 human melanoma line demonstrated that α‐tocopherol supplementation did not influence the efficacy of DDP; the inhibition of cell survival and of the in vivo tumor growth after treatment with α‐tocopherol and DDP combination was similar to that observed after DDP alone. Conversely, α‐tocopherol was also able to increase survival of mice treated with a high dose of DDP. While DDP alone produced death in about 70% of mice, the combination reduced deaths to about 30%. Analysis of oxidative stress markers and peroxidative damage in organs indicated that the protective effect of α‐tocopherol was mainly related to its antioxidant activity. A significant increase in the concentration of TBARS and decreased PUFAs and catalase activity were observed after DDP treatment, while with α‐tocopherol the levels of these markers were comparable to those observed in untreated mice. Histologic analysis performed on peripheral nerve revealed that α‐tocopherol also protected mice from severe neurologic damage induced by DDP treatment. In conclusion, our results demonstrate that α‐tocopherol protects against the systemic toxicity and neurotoxicity induced by DDP without interfering with its antitumor activity and suggest that this combination is a promising strategy to improve the therapeutic index of DDP‐based chemotherapy.

Weekly schedule of vinorelbine in pretreated breast cancer patients

AbstractPurpose: In this phase II study, we explored tolerability and activity of vinorelbine administered according to a dose-dense weekly schedule with hematopoietic growth factor support in pretreated, advanced breast cancer patients.nPatients and Methods: From January 1994 to March 1996, 40 patients with metastatic breast cancer, pretreated with at least one prior anthracycline-containing regimen, were entered into the study. Patient characteristics: median age 53 years (range 32–70); ECOG performance status 0-1: 34 patients, 2: 6 patients; dominant visceral metastatic disease: 15 patients, dominant non-visceral: 25; anthracycline-refractory/resistant: 2 patients, sensitive: 38 patients. Six patients were treated as first-line therapy for metastatic disease and 34 in second- or subsequent lines.All patients received vinorelbine at the dose of 25 mg/m2/week as a short intravenous infusion, together with routine antiemetic medication. Granulocyte-colony stimulating factor (Lenograstim) at the dose of 150 μg/m2 subcutaneously on day 3 was included in the treatment schedule.nResults: The median number of treatment weeks was 23 (range: 4–24), with a delivered dose-intensity (DDI) of 23.8 mg/m2/week (range: 18.7–25, 95.2% of projected dose-intensity).Toxicity was mild, with non-complicated neutropenia being the main toxicity observed (grade 3–4 in 25% of the patients but only 2% of treatment weeks). Overall response rate was 52.5%, with complete responses in 12.5% of patients. Median duration of the response and median time to progression were 10 and 9 months, respectively. Median overall survival was 19 months.nConclusion: Dose-dense weekly vinorelbine is safe and effective with minimal toxicity in pretreated advanced breast cancer patients.

Neurophysiological evaluation of sexual dysfunction in patients operated for colorectal cancer

Sexual dysfunction after colorectal cancer surgery may be severe and occurs in 25% to 100% of cases. Thirty-eight patients underwent colorectal resection; eight (21%) who were totally impotent and two (5%) who had ejaculatory failure were therefore studied to better understand the neurophysiological alterations related to this type of surgery.The patients were evaluated after surgery with electrophysiological testing, including examination of the sacral reflex (SR), pudendal somatosensory evoked potential (PEP), and motor evoked potential (MEP) responses. Sudomotor skin response (SSR) was also studied in a group of patients. Of the 38 patients studied, 29 showed abnormalities: six of SR, three of PEP, six of MEP, and fourteen of SSR. Only a combination of all these tests permits correct evaluation of the sexual dysfunction.

Neuroprotective effect of vitamin e supplementation in patients treated with cisplatin-based chemotherapy

PURPOSEnThe aim of this study is to evaluate the neuroprotective effect of antioxidant supplementation with vitamin E in patients treated with cisplatin chemotherapy.nnnMETHODSnBetween 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.nnnRESULTSnTwenty-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.nnnCONCLUSIONnSupplementation of patients receiving cisplatin chemotherapy with vitamin E decreases the incidence and severity of peripheral neurotoxicity.