Increased risk and early onset of ALS in professional players from Italian Soccer Teams

Objective: Since the observation of several deaths from amyotrophic lateral sclerosis (ALS) among Italian professional soccer players, an association between ALS and soccer has been postulated. The objective of the study is to investigate the association between professional soccer and the risk of ALS in a large cohort of former professional soccer players with prolonged follow-up. Methods: All professional soccer players practicing in the period 1959–2000 were identified through the archives of an Italian soccer cards publisher. For each player, date and place of birth, playing role, and team history were recorded. Each player was followed since 15 years of age. Incident ALS cases were all soccer players first diagnosed during the period 1959–2018. The expected incidence rate was the number of ALS cases/100,000 person-years expected in the cohort. SIR was the ratio between observed and expected incidence rate. Results: 34 ALS cases were detected. The number of expected cases was 17.8. The SIR was 1.91 (95% CI 1.32–2.67) in the entire sample and 4.66 (95% CI 2.66–7.57) in subjects aged less than 45 years. The mean age at diagnosis was 45.0 years. Compared to the mean age of onset of ALS in the general population (65.2 years), the disease in former soccer players occurred 20.2 years earlier. Conclusions: Professional soccer players are at higher risk of developing ALS than the general population. Soccer players with ALS develop the disease at a younger than expected age

A randomized phase II study of combination, alternating and sequential regimens of doxorubicin and docetaxel as first-line chemotherapy for women with metastatic breast cancer

Background: This randomized phase II study was conducted to evaluate the efficacy of doxorubicin and docetaxel (DOC) administered either as a combination, an alternating or a sequential regimen in women with metastatic breast cancer. Secondary objectives included overall response, time to progression, survival and safety. Patients and methods: Patients with breast cancer (n = 123) were randomized to receive doxorubicin and DOC either in combination (60 mg/m(2) of each drug), or by alternated or sequential schedule (100 mg/m(2) DOC and 75 mg/m(2) doxorubicin) every 3 weeks for a maximum of eight cycles as first chemotherapy for stage IV disease. A second randomization allocated patients from each arm to receive prophylactic oral ciprofloxacin or no therapy to prevent febrile neutropenia. Results: Patients received a median of eight cycles. In an intention-to-treat analysis, the overall response was 63%, 52% and 61% in the combination, alternating and sequential schedules, respectively. Corresponding rates of complete response were 15%, 14% and 11%. Grade 4 neutropenia was common in all arms (81%) and, together with febrile neutropenia, was significantly more frequent with the combination. Prophylaxis with ciprofloxacin did not reduce the incidence of febrile neutropenia or infection. Other frequent non-hematological adverse events included alopecia, nausea, vomiting, stomatitis and asthenia. Congestive heart failure only occurred in the combination arm (10%). Conclusion: All three schedules are feasible and endowed of good therapeutic activity. In view of the more pronounced toxicity and the risk of cardiac events because of the higher exposure to doxorubicin, the combination should be least favored when treating women with metastatic breast cancer. Prophylaxis with ciprofloxacin was ineffective and is not recommended

Toxicity and clinical tolerance of lonidamine

The new anticancer agent lonidamine has been recently revisited for the treatment of various solid tumors, due to its peculiar and unusual mechanism of action (ie, interference with energy metabolism of tumor cells, morphologically displayed by the appearance of "condensed mitochondria"). First generation trials have in fact demonstrated therapeutic activity and an unusual toxicity profile. Lonidamine is devoid of conventional side effects induced by antiproliferative agents (ie, myelosuppression, stomatitis, cystitis, alopecia, renal, hepatic, and cardiac toxicity). No serious or life-threatening adverse reactions have been recorded even over long term treatment periods. Given as a single agent (in daily doses ranging between 300 and 900 mg) lonidamine induces the following side effects: myalgia, testicular pain, asthenia, ototoxicity, nausea and vomiting, gastric pain, and drowsiness. Hyperesthesia and photophobia have also been reported. In combination with radiotherapy (in oral daily doses ranging between 300 and 450 mg) lonidamine was well tolerated, without any reported evidence of additional toxicity. When associated with cytotoxic agents no enhanced toxicity was observed. In particular, myelosuppression and other conventional nonhematological adverse reactions were never greater than would be expected with chemotherapy alone. The same applies to toxicity and tolerance of lonidamine when used concurrently with hypertermia. The data collected from large series of cancer patients treated with this new agent show that lonidamine is a safe drug whether used alone or in combination with other effective anticancer treatments. The reported therapeutic efficacy and the peculiar toxic profile make lonidamine an interesting new drug for future clinical trials

Somatic mutations at the T-cell antigen receptor in antineoplastic drug-exposed populations: comparison with sister chromatid exchange frequency

OBJECTIVE: The objective of this study was to assess the genetic effect of occupational exposure to antineoplastic agents. METHOD: The influence of occupational handling of cytotoxic drugs was investigated by monitoring the frequency of sister chromatid exchanges (SCE), the percentage of cells with high frequencies of SCE (high-frequency cells, HFC), and the frequency of somatic mutation at the T-cell receptor (TCR) locus in mononuclear cells of exposed hospital nurses. These parameters were also measured in healthy donors and in cancer patients at the time of the diagnosis and following the administration of high doses of cytotoxic drugs requiring stem cell support. RESULTS: Our results show that (a) SCE and HFC values in occupationally exposed nurses do not differ from controls, (b) patients with newly diagnosed cancer or following chemotherapy show a number of SCE comparable to those of healthy donors, but a significantly different percentage of HFC, (c) cigarette smokers of all categories studied show higher frequencies of SCE and HFC as compared to nonsmokers, but the differences are not statistically significant, (d) the mutation frequency at the TCR locus in oncology nurses is higher, but not significantly different from the frequency in the control group, and (e) the increase of mutation frequency is statistically significant and seems to be dose dependent in patients treated with high-dose chemotherapy. CONCLUSIONS: Our data suggest that SCE frequency and HFC percentage are not reliable indicators of exposure to possible mutagenic/carcinogenic effects of antineoplastic drugs; on the contrary, our observations indicate that anticancer therapy induces somatic mutations at the TCR locus and suggest an association between exposure to cytotoxic agents and the increase in somatic mutations