Comparison between Acupuncture and Nutraceutical Treatment with Migratens® in Patients with Fibromyalgia Syndrome: A Prospective Randomized Clinical Trial.

OBJECTIVES: Fibromyalgia syndrome (FMS) is a chronic clinical condition characterized by pain, fatigue, altered sleep, and cognitive disturbances. The purpose of this study was to compare two alternative treatments (nutraceutical and acupuncture) in FMS patients through a randomized clinical trial. RESEARCH METHODS: A total of 60 FMS female patients were randomized for treatment with a nutritional combination containing coenzyme Q10, vitamin D, alpha-lipoic acid, magnesium, and tryptophan (Migratens® Group) or acupuncture treatment (Acupuncture Group) performed according the principles of traditional Chinese medicine (TCM), both for 3 months. Changes in pain and in quality of life (QoL) measured with a Fibromyalgia Impact Questionnaire Score-Revised (FIQ-R) and the Fibromyalgia Severity Scale (FSS) were performed at 1, 3, and 6 months after the start of treatments. RESULTS: A total of 55 patient completed the study (21 in the Migratens® Group and 34 in the Acupuncture Group). Migratens® treatment shows a statistically significant reduction of pain 1 month after the start of therapy (T1, p = 0.025), strengthened after 3 months with maintenance of treatment (p = 0.012). The efficacy in reducing pain was apparent in the Acupuncture Group at all post-treatment determinations and at follow-up (T1 and T2 p = <0.001). Regarding QoL, improvement in FIQ-R and FSS values was revealed in both groups. CONCLUSION: The nutraceutical approach with Migratens® seems to be an effective option to for patients with FMS. Our experience confirmed also the validity of acupuncture in these patients. Considering the complexity of the management of FMS patients, our results suggest a cyclical and sequential, or even concurrent treatment with different approaches, to improve the efficacy and the compliance of patients to long-term treatment.

Morphological study of upper airways and long-term follow-up of obstructive sleep apnea syndrome in acromegalic patients.

Pathogenesis and long-term outcome of obstructive sleep apnea syndrome (OSAS) in acromegalic patients are still under debate. The aim of the study was to assess the prevalence and long-term follow-up of a series of acromegalic patients with OSAS and to investigate site, degree, and possible causes of upper airway obstruction by morphological study. Cross-sectional and longitudinal study was conducted in 58 acromegalic patients (33 active, 25 controlled) with polysomnography in all subjects, repeated in 25 patients with OSAS, and echocardiography. Morphological study including fiberoptic nasopharyngoscopy with the Müller maneuver (FNMM), magnetic resonance imaging (MRI), with 3-dimensional (3D) elaboration was also performed. The prevalence of OSAS was 58.6 % in the whole series: 63.6 % in the active group and 52 % in the controlled one. Left ventricular hypertrophy was more prevalent in patients with OSAS. OSAS improved in 62.5 % of active patients after achieving hormonal control, whereas it persisted or got worse in 66.6 % of the controlled ones. The uvula and tongue base were the main site of obstruction assessed by FNMM. Uvula diameters obtained by MRI study correlated with the severity of upper airway collapse assessed by FNMM and tongue measure with apnea-hypopnea index (p = 0.044). A greater narrowing and a smaller total volume of upper airways were confirmed by 3D-MRI in patients with more severe OSAS. Uvula and tongue hypertrophy plays a relevant role in the pathogenesis and severity of OSAS. Intensive treatment of acromegaly needs to be promptly adopted in order to reverse it.

Noninferiority trials in second-line treatments of nonsmall cell lung cancer: a systematic review of literature with meta-analysis of phase III randomized clinical trials.

BACKGROUND: To assess the role of the novel second-line treatments in nonsmall cell lung cancer (NSCLC). METHODS: A systematic review of the literature with meta-analysis of phase III randomized clinical trials (RCTs) was independently performed by 3 authors. All the trials comparing any novel treatment with every-3-weeks docetaxel (3WD) and designed as noninferiority trial were included in the analysis. One-year survival rate (SR) was the primary end point, and quality of life and safety represented the secondary end points. RESULTS: Four RCTs met the selection criteria. The outcomes of 3355 patients were analyzed in the pooled analysis. No heterogeneity was documented in the primary analysis either including all the trials or analyzing separately gefitinib and the chemotherapeutic alternatives to 3WD. The cumulative odds ratio was 0.927 (P=0.313) for 1-year SR, 0.889 (P=0.323) for the chemotherapeutic alternatives to 3WD and 0.953 (P=0.616) for gefitinib. The experimental arms showed a significant advantage in quality of life in the cumulative analysis (odds ratio=1.623, P=0.01) and in the subgroup of patients treated with gefitinib (odds ratio=1.962, P<0.001); a better safety profile for the experimental arm was observed in the cumulative analysis and in the subgroups of alternative chemotherapies or gefitinib. CONCLUSION: All the noninferiority trials demonstrated the noninferiority of pemetrexed, oral topotecan, or gefitinib in 1-year SR (primary end point), but the improvement in overall survival remains modest. The improvement in quality of life and safety (secondary end points) represents the main value of these treatments, whose aim is mainly palliative.

Bevacizumab in the treatment of advanced, non-squamous non-small cell lung cancer: an evidence-based approach.

BACKGROUND: To assess the efficacy and safety of bevacizumab-containing regimens in the treatment of advanced, chemotherapy-naive, non-squamous non-small cell lung cancer (NSCLC) on the basis of the two registrative trials [ECOG E4599 trial and BO17704 (AVAiL) trial]. METHODS: A pooled analysis of the two trials was performed using a random effect model, and the results were summarized as number-needed-to-treat (NNT) and number-needed-to-harm (NNH). A 2-step analysis was performed. The primary analysis included only the patients treated with bevacizumab 15 mg/kg in the experimental arm, whereas the secondary analysis (with descriptive aim) included the patients treated with bevacizumab 15 mg/kg or those treated with bevacizumab 7.5 mg/kg in the experimental arm. The 1-year survival and 6-month progression-free rates were assumed as indexes of efficacy, and grade III-IV side effects were assumed as index of safety in both analyses. RESULTS: 1,921 patients were potentially eligible for the pooled analysis and were included in the secondary analysis, whereas 1,576 patients were included in the primary analysis. A large heterogeneity was documented for both 6-month progression-free interval (I(2) = 88.164%, p = 0.004) and overall survival (I(2) = 73.541, p = 0.052). The absolute risk reduction of 1-year death and 6-month progression were 3.3% (95% CI = -6.5 to 13.2%, p = 0.507), with a NNT = 30; and 15.2% (95% CI = 0.07-29.6%, p = 0.04), with a NNT = 6 (both in favor of the bevacizumab-containing regimens), respectively. The absolute risk of treatment-related death was 2.4% (95% CI = 0.8-3.9%, p = 0.003), with a NNH = 41 against the bevacizumab-containing regimens; that of bleeding was 3.3% (95% CI = 1.6-4.9%, p < 0.001), with a NNH = 30; that of hypertension was 6.6% (95% CI = 4.6-8.6%, p < 0.001), with a NNH = 15; that of proteinuria was 2.1% (95% CI = 0.3-3.8%, p = 0.024), with a NNH = 47; that of neutropenia was 7.3% (95% CI = 3.2-11.4%, p < 0.001), with a NNH = 13; that of thrombocytopenia was 1.5% (95% CI = 0.2-2.7%, p = 0.021), with a NNH = 66. No significant differences were observed in the efficacy and the safety analysis when all the patients treated with bevacizumab 7.5 mg/kg and 15 mg/kg were included into the pooled analysis. CONCLUSION: Adding bevacizumab to standard chemotherapy in the treatment of advanced, chemotherapy-naive, non-squamous NSCLC seems to favor a modest improvement in the main outcomes, with a significant worsening of the safety profile. These data suggest caution in the generalized use of bevacizumab-containing regimens in the treatment of advanced, chemotherapy-naive, non-squamous NSCLC.

[Neuropathic pain in oncology. Novel evidence for clinical practice]. / Il dolore neuropatico in oncologia. Nuove evidenze per la pratica clinica.

Neuropathic pain is usually considered an "hard pain" both for the intrinsic difficulties in a correct diagnosis, and for the modest efficacy of the most part of conventional treatments. The most frequently used drugs in clinical practice are tricyclic antidepressants and anticonvulsants, while a minor role is reserved to NSAIDs or to strong opiates. Aim of our work was to systematically analyze all the evidences of literature about the treatment options against neuropathic pain in oncology, focusing our attention upon the efficacy and the safety of the different therapeutic options assessed as Number-Needed-to-Treat (NNT) and Number-Needed-to-Harm (NNH). A critical analysis of literature was finally performed using the GRADE system. On the basis of our review and the NNT and NNH ratio, gabapentin, pregabalin and strong opiates seem to be the most effective and well tolerated options against neuropathic pain in oncology, while carbamazepine, amitryptiline, tramadol and NSAIDs do not seem to be valid options in front line approach against oncologic neuropathic pain, either for a minor efficacy or for an unfavorable safety profile. Further trials comparing the different effective options are needed to better define the correct approach against neuropathic pain in oncology.

Lipoplatin treatment in lung and breast cancer.

The introduction of cisplatin in cancer treatment represents an important achievement in the oncologic field. Many types of cancers are now treated with this drug, and in testicular cancer patients major results are reached. Since 1965, other compounds were disovered and among them carboplatin and oxaliplatin are the main Cisplatin analogues showing similar clinical efficacy with a safer toxicity profile. Lipoplatin is a new liposomal cisplatin formulation which seems to have these characteristics. Lipoplatin was shown to be effective in NSCLC both in phase 2 and phase 3 trials, with the same response rate of Cisplatin, a comparable overall survival but less toxicity. A new protocol aiming to elucidate the double capacity of Lipoplatin to act as a chemotherapeutic and angiogenetic agent in triple-negative breast cancer patients is upcoming.

[Transdermal opiates in the treatment of moderate-severe cancer pain. Recommendations for clinical practice]. / Oppiacei transdermici nel trattamento del dolore oncologico moderato-severo. Raccomandazioni per la pratica clinica.

Although oral morphine is the gold standard in the front-line approach to moderate-severe cancer pain, transdermal opiates are largely used in clinical practice. Aims of our work were to review the evidences of literature supporting these different habits and to suggest an evidence-based criterion to guide clinical research and clinical practice. A systematic review of literature with meta-analysis of the safety data reported in randomized clinical trials comparing slow releasing oral morphine and transdermal opiates was performed using the random effect model. The quality of the evidences supporting the use of the different strategies and the strength of the recommendations was analyzed using the GRADE method. A significant advantage in favor of transdermal opiates was observed for constipation, urinary retention, need of laxative use and patient's preferences; a significant advantage in favor of slow releasing oral morphine was observed for diarrhea and sweating. The quality of the evidences supporting a front-line use of transdermal fentanyl was considered low, while those supporting the use of transdermal buprenorphine was considered very low. For the use oftransdermal fentanyl and for that oftransdermal buprenorphine a weak and a strong recommendation against their us as front-line treatment of moderate-severe cancer pain can be respectively obtained from the literature data. Transdermal opiates represent a safety and effective alternative to oral morphine against cancer pain, but they can not replace oral morphine as the gold standard first-line treatment of moderate-severe cancer pain.