Early Docetaxel and Androgen Deprivation in the Treatment of Metastatic, Hormone-sensitive Prostate Cancer.

BACKGROUND: To assess the role of docetaxel plus androgen deprivation in metastatic, hormone- sensitive prostate cancer. METHODS: A qualitative systematic review of literature was performed. All the randomized phase III trials comparing docetaxel plus androgen deprivation with androgen deprivation alone in patients with metastatic, hormone-sensitive prostate cancer were considered eligible and included into the analysis. RESULTS: Six papers (3 randomized clinical trials, and 3 systematic reviews with meta-analysis) were considered eligible and included into the analysis. A significant improvement in time to progression and OS in the entire population treated with docetaxel plus androgen deprivation was reported in all the trials and meta-analyses, and in two trials and all meta-analyses, respectively. One trial reported improvement of OS only in patients with high volume disease, and the meta-analysis that also analyzed the subgroups of patients with high or low volume disease reported a benefit of docetaxel plus androgen deprivation for either the entire population or the two subgroups of patients. CONCLUSION: The early use of docetaxel combined with androgen deprivation improves the main outcomes in the treatment of metastatic, hormone-sensitive prostate cancer. The available data suggest that docetaxel plus androgen deprivation could be considered the novel standard for fit patients with metastatic, hormone-sensitive prostate cancer.

Maintenance based Bevacizumab versus complete stop or continuous therapy after induction therapy in first line treatment of stage IV colorectal cancer: A meta-analysis of randomized clinical trials.

BACKGROUND: In stage IV colorectal cancer, bevacizumab-based maintenance therapy, complete stop therapy and continuous therapy are considered all possible approaches after first line induction chemotherapy. However, there are no clear data about which approach is preferable. MATERIAL AND METHODS: All randomized phase III trials comparing bevacizumab-based maintenance therapy (MB) with complete stop therapy (ST) or with continuous therapy (CT) were considered eligible and included into the analysis. Primary endpoint was the Time to failure strategies (TFS). Secondary endpoints were Overall Survival (OS) and Progression free survival (PFS). Meta-analysis was performed in line with the PRISMA statement. RESULTS: 1892 patients of five trials were included into the analysis. A significant improvement in TFS (HR 0.79; CI 95% 0.7-0.9 p=0.0005) and PFS (HR 0.56; CI 95% 0.44-0.71 p<0.00001) were observed in favour of MB versus ST. A trend, but not statistically significant, in favour of MB versus ST was also observed for OS (HR 0.88; CI 95% 0.77-1.01, p=0.08). Comparing maintenance therapy versus continuous therapy no statistically differences were observed in the outcomes evaluated (OS 12 months OR 1.1 p=0.62, OS 24 months OR 1 p=1, OS 36 months OR 0.54 p=0.3, TFS 12 months OR 0.76 p=0.65). CONCLUSIONS: Our meta-analysis suggests that use of MB approach increases TFS, PFS compared to ST. Although without observing any statistically advantage, it should be highlighted that MB versus ST showed a trend in favour of MB. We observed no difference between MB and CT. MB should be considered the standard regimen in patients with stage IV colorectal cancer after first line induction therapy.

[Radically resected pancreatic cancer and adjuvant treatment. A review of the literature]. / Carcinoma del pancreas resecato radicalmente e terapia adiuvante. Revisione della letteratura.

Adjuvant therapy represents the gold standard treatment for radically resected pancreatic cancer. Results from randomized clinical trials confirmed the efficacy of adjuvant therapy for pancreatic cancer but did not define what is the "right choice" in terms of type of antiblastic drug (among gemcitabine, 5-fluorouracil or other drugs), role of polychemotherapy and chemoradiotherapy. The objective of our study was to evaluate the efficacy and toxicity of adjuvant chemotherapy and chemoradiotherapy for radically resected pancreatic cancer through a systematic review of literature data, emphasizing the benefits regarding overall survival, disease-free survival and toxicity.

Long lasting clinical response to chemotherapy for advanced uterine leiomyosarcoma: a case report.

INTRODUCTION: Uterine leiomyosarcoma is one of the most frequent uterine sarcomas. In the metastatic setting it is sensitive to doxorubicin, ifosfamide, gemcitabine, docetaxel and a few other drugs, but time to progression is generally short. For this reason prognosis is often poor and there are few reports in the literature of long responders. CASE PRESENTATION: We report a case of a 40-year-old Caucasian woman with metastatic uterine leiomyosarcoma who began treatment six years before the presentation of this case report and for the following six years underwent ten lines of chemotherapy, achieving excellent results and a good quality of life. Among the treatments administered we observed a long response to temolozomide, an unconventional drug for this kind of disease. CONCLUSION: Although there are few chemotherapeutic options for the management of metastatic uterine leiomyosarcoma, a small number of patients have an unexpected long lasting response to treatment. For this reason further research is needed to identify new therapeutic agents and the predictive factors for the achievement of response.

[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 fentanyl as a front-line approach to moderate-severe pain: a meta-analysis of randomized clinical trials.

OBJECTIVE: The safety of transdermal fentanyl (TF) in comparison with slow-release oral morphine (SROM) in moderate-severe pain was assessed. DESIGN: A systematic review of the literature was performed to identify all randomized trials comparing TF and SROM in moderate-severe pain. Overall safety was the primary end point. Trials enrolling both cancer and non-cancer patients were included in the analysis. Heterogeneity was assessed using the Mantel-Haenszel test; a random effects model was used for the pooled analysis. Cumulative and distinctive analyses for cancer and non-cancer pain were performed whenever the outcome was reported in at least two trials. RESULTS: Five trials met the inclusion criteria. A significant advantage of TF was documented for constipation, laxative use, and urinary retention. TF was preferred by cancer and non-cancer patients. A difference in favour of SROM was documented for nausea, diarrhea, and sweating in cancer and non-cancer patients. No differences were observed for the other items considered. CONCLUSIONS: TF and SROM seem to have a different side effects profile, and TF seems to be preferred by patients. The hierarchical approach traditionally recommended by the main scientific societies (oral morphine and then TF) could be replaced by a front-line approach based on patients' characteristics and needs.

Second-line treatments in non-small cell lung cancer. A systematic review of literature and metaanalysis of randomized clinical trials.

BACKGROUND: To assess the efficacy of second-line treatments in non-small cell lung cancer (NSCLC). METHODS: A systematic review of literature with metaanalysis of randomized clinical trials (RCTs) was independently performed by three authors. A primary analysis included all RCTs comparing any approach (chemotherapy or therapy with epidermal growth factor receptor [EGFR] inhibitors) with placebo; a secondary analysis included all RCTs comparing any treatment with docetaxel therapy every 3 weeks. The 1-year survival rate (SR) of the primary analysis was the primary outcome of the study; the 1-year SR of the secondary analysis, response rate (RR), and time to progression of primary and secondary analyses were the secondary end points. RESULTS: Fourteen RCTs met the selection criteria. The outcomes of 2,627 and 5,952 patients were analyzed in the primary and secondary analysis, respectively. A significant heterogeneity was documented in the primary analysis for 1-year SR with odd ratio [OR] = 0.763 (p = 0.029). No heterogeneity was documented for RR in the primary analysis, with OR = 0.165 (p < 0.001). A modest heterogeneity was documented in the secondary analysis for 1-year SR and RR, with 1-year SR OR = 0.924 (p = 0.122) and RR OR = 1.069 (p = 0.643). CONCLUSION: Second-line treatments in NSCLC seem to improve the main outcomes better than supportive care. Docetaxel administration every 3 weeks probably remains the "gold standard" because at present the data in literature are not enough to support a greater efficacy of other alternative options. Further trials are needed to identify a clinical and biological profile that could predict the response to treatments and a criterion to select the patients to be treated with chemotherapy or EGFR inhibitors.

Second line treatments in advanced platinum-resistant non small cell lung cancer. A critical review of literature.

In the last 10 years the medical approach to platinum-resistant Non Small Cell Lung Cancer (NSCLC) has radically changed, passing from a lack of evidence of any primary treatment against the tumor, to the identification of chemotherapy or EGFR inhibitors as the gold standard for clinical practice. Eight randomized clinical trials support the evidence of efficacy of second-line treatments against NSCLC, and docetaxel, pemetrexed and erlotinib are the most effective options for clinical practice. However, many aspects remain still undefined: Can a treatment with docetaxel, pemetrexed or erlotinib be considered the gold standard for all patients with platinum-resistant NSCLC, and consequently should all patients be treated with at least one of these options? Are the benefits enough to justify the side effects observed with these chemotherapeutic options? Can a schedule be preferred to the others for either efficacy or safety profile? Can the new EGFR inhibitors be considered an innovation in the treatment of platinum-resistant NSCLC, and should they be used in all patients with platinum-resistant NSCLC? A systematic review of randomized clinical trials and a critical analysis of the results were performed with the aim to clarify the real meaning of medical treatments in advanced, platinum-resistant NSCLC.