Treatment of Metastatic, Castration-resistant, Docetaxel-resistant Prostate Cancer: A Systematic Review of Literature With a Network Meta-analysis of Randomized Clinical Trials.

INTRODUCTION: To compare the efficacy of abiraterone acetate, enzalutamide, cabazitaxel and Radium-223 in the treatment of castration-resistant, docetaxel-resistant metastatic prostate cancer. METHODS: An indirect comparison of Overall Survival (OS) and time to PSA progression among abiraterone acetate, enzalutamide, cabazitaxel and Radium-223 was performed with a network metaanalysis. OS in the entire population of patients was the primary endpoint. OS in ECOG 0-1/2, BPISF≤ 4/>4, pretreated with 1 or 2 courses of chemotherapy, age≤65/>65 patients, patients with only bone metastases or bone and visceral metastases, and time to PSA progression were the secondary endpoints. An indirect comparison of the Hazard Ratio and the 95% Confidence Interval was performed, assuming an alpha error of 5% as an index of statistical significance. The among-the-trial heterogeneity was assessed using a qualitative methodological and clinical analysis. RESULTS: Four trials were selected. In three trials, the comparator was placebo, in one trial it was mitoxantrone, the effect of which in improving survival was considered negligible. No significant difference in OS among abiraterone acetate, enzalutamide, cabazitaxel and radium 223 was observed in neither the entire population nor all the subgroups of patients. Enzalutamide resulted significantly better than abiraterone acetate, cabazitaxel or radium-223 in time to PSA progression. CONCLUSION: Since no significant difference in efficacy seems to exist between the four therapeutic options in the treatment of castration-resistant, docetaxel-resistant, metastatic prostate cancer, the safety of the treatment, patient's compliance and costs should represent the criteria to guide clinicians' choice in clinical practice.

Antimetabolites in the treatment of advanced pleural mesothelioma: a network meta-analysis of randomized clinical trials.

An indirect comparison of cisplatin-pemetrexed (CP) and cisplatin-raltitrexed (CR) was performed. The Odds Ratios of 10, 15 and 20 month survival rate and response rate were assumed as indexes of efficacy; the Odds Ratio of grade III-IV side effects, and the absolute risk of overall, hematologic and non-hematologic toxicity, were assumed as indexes of safety. The outcomes of 352 patients were analysed. The Odds Ratios and 95% Confidence Interval (95% CI) of 10, 15 and 20 months survival rate and response rate were 1.2 (95% CI 0.65-2.24, p = 0.559), 1.02 (95% CI 0.49-2.12, p = 0.953), 1.13 (95% CI 0.44-2.91, p = 0.805) and 0.56 (95% CI 0.26-1.21, p = 0.141), respectively. An absolute increased risk of grade III-IV side effects was observed for CP: 6% (95% CI 3-9%, p < 0.001), 9% (95% CI 2-16%, p = 0.008) and 3% (95% CI 0-5%, p = 0.035) for overall, hematological and non-hematological toxicity. CP and CR can be considered comparable in terms of efficacy in the treatment of metastatic pleural mesothelioma, with a modest increased risk of grade III-IV side effects for CP.

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.

Early Palliative Care in Advanced Oncologic and Non-Oncologic Chronic Diseases: A Systematic Review of Literature.

BACKGROUND: To assess the role of early palliative care in patients with advanced oncologic and non-oncologic chronic diseases. METHODS: A qualitative systematic review of literature was performed. All the randomized phase III trials comparing early, simultaneous palliative care and standard care in patients with advanced oncologic and non-oncologic diseases were considered eligible and included into the analysis. The outcomes were classified into 6 classes: quality of life, symptoms control, overall survival, quality of care, patients' and caregivers' satisfaction, and costs of the assistance. RESULTS: Twelve papers reporting the data of 9 trials were considered eligible and included into the analysis. Two nonrandomized trials were also included into the selection because of the methods used by the authors. The early, simultaneous approach was reported to improve quality of life in two out of 7 papers, symptoms control in 1 out of 5 papers, overall survival in 2 out of 3 papers, quality of care in 5 out of 8 papers, patients' or caregivers' satisfaction in 3 out of 4 papers; and to reduce the costs of assistance in 2 out of 3 papers. CONCLUSION: Early palliative care improves the main outcomes of the assistance in patients with advanced oncologic and non-oncologic chronic diseases. The available data are probably enough to consider early palliative cares a novel standard of care in these groups of patients.

[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.

Ovarian cancer in elderly patients: a difference in treatment based on age?

PURPOSE: The aim of this study was to examine if treatment strategies differ by age in the elderly population with ovarian cancer in daily clinical practice. METHODS: A retrospective analysis of elderly patients with ovarian cancer who were referred to our institution between January 2007 and August 2010 was done. A univariate analysis for overall survival was estimated according to the Kaplan-Meier method, censoring surviving patients at the time of last follow-up. RESULTS: We evaluated 32 elderly patients: 17 "young-old" patients (65-74 years old), 14 "old-old" patients (75-84 years old) and 1 "oldest-old" patient (≥85 years old). At last follow-up, 20 patients (62.5%) were alive and 12 patients (37.5%) were deceased. Median time follow-up was 18.52 months. Median overall survival was 19.05 months. Median age was 73.50 years. In the subgroup of "young-old" patients, there were less "high malignant potential" (64.3 vs. 70.0%) and grade 3 ovarian cancers (84.6 vs. 90.0%), less advanced stages (III-IV: 64.7 vs. 86.7%), higher number of optimal surgical procedures (50.0 vs. 30.0%) and more frequent use of chemotherapy (82.4 vs. 66.7%). Single agent carboplatin was administered in 81.8 vs. 77.8% of "young-old" and "old-oldest old" patients, and average number of lines was 2 vs. 1. Other characteristics were similar in the two subgroups ("young-old" vs. "old-oldest old" patients). By the univariate analysis, there was no statistical significance difference in overall survival (p=0.393) between the two subgroups, with only a positive trend for young-old patients. CONCLUSIONS: In old- and oldest-old patients, the characteristics of disease are worse and optimal treatment strategy is less frequently applied. The management of patients by multidisciplinary team is needed and it could better individualize and apply the optimal treatment approach.

Immunotherapy and targeted therapies in metastatic renal cell carcinoma: is there a preferred sequence?

INTRODUCTION: Currently, the best sequence of targeted therapy in patients with metastatic renal cell carcinoma (mRCC) has not been sufficiently defined and is based on the patient's and physician's decision, which may be influenced by comorbidities and toxicity profiles. The aim of this study was to evaluate the outcome of target therapies on clinical practice after the era of cytokine-based therapy in mRCC. MATERIALS AND METHODS: We retrospectively analyzed all consecutive patients with mRCC treated at our Clinical Oncology Unit from June 1998 to September 2010. RESULTS: We evaluated 61 patients: 21 (34.4%) with only cytokine-based therapy (95.2% interferon-α), 24 (39.3%) with target therapies in first line (100% sunitinib), and 16 (26.2%) with target therapies in second or subsequent line. Median time follow-up was 16.18 months (range 2.1-171.1). Considering the type of therapy, the univariate analysis for overall survival showed statistically significant advantages for the use of target therapies in second or subsequent line (p=0.024). CONCLUSIONS: Our data and consequently our proposal to revaluate the role of immunotherapy (also with the possibility of adding bevacizumab) in the first line are heavily provocative to point out the attention to this actually partially unsolved question; other larger experiences, pre-eminent opinion, and clinical trials are needed.

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.

The second step of the analgesic ladder and oral tramadol in the treatment of mild to moderate cancer pain: a systematic review.

BACKGROUND: To analyse the evidence supporting the widespread use of modified analgesic ladders or oral tramadol as alternatives to codeine/paracetamol for mild to moderate cancer pain. METHODS: A systematic review of the literature was independently performed by two authors. The level of evidence and risk/benefit ratio were assessed in all the selected trials. A comprehensive analysis of the level of evidence, risk/benefit ratio and strength of the recommendations was carried out. The analysis was performed using the GRADE system. RESULTS: Eighteen papers were included into the analysis. The level of evidence was low or very low for all the trials, and as a result the risk/benefit ratio was uncertain. Likewise, the strength of the final recommendations was considered weak negative for either the use of modified analgesic ladders (by-passing the second step of the World Health Organization (WHO) analgesic ladder) or the use of oral tramadol as an alternative to codeine/paracetamol in the second step of the WHO analgesic ladder. CONCLUSIONS: Data supporting the role of modified two-step analgesic ladders or oral tramadol as an alternative to codeine/paracetamol are insufficient to recommend their routine use in cancer patients with mild to moderate cancer pain.

Transdermal opioids as front line treatment of moderate to severe cancer pain: a systemic review.

BACKGROUND: To assess the role of transdermal opioids as a front-line approach to moderate to severe cancer pain. METHODS: A systematic review of the literature was performed by two authors. An analysis of the level of evidence and risk/benefit ratio was performed for all of the selected trials. A combined analysis of the included studies to assess the level of evidence, risk/benefit ratio and strength of the recommendations was performed to determine the place of transdermal opioids in the treatment of cancer when compared with oral morphine. RESULTS: Thirteen papers were included in the analysis. The level of evidence was considered low for transdermal opioids (without distinction between transdermal fentanyl and transdermal buprenorphine) or transdermal fentanyl, and very low for transdermal buprenorphine. The risk/benefit ratio was considered uncertain for both transdermal opioids (fentanyl and buprenorphine) considered together and transdermal fentanyl or buprenorphine alone. The strength of the final recommendations (using the GRADE system) was weak negative for transdermal opioids (transdermal fentanyl plus transdermal buprenorphine) and transdermal fentanyl, and strong negative for transdermal buprenorphine. CONCLUSIONS: The use of slow release oral morphine probably remains the preferred approach for these patients, with the use of transdermal opioids to be reserved for selected patients.

[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.

Toxic encephalopathy in elderly patients during treatment with capecitabine: literature review and a case report.

Capecitabine is now-a-days rapidly replacing 5-Fluorouracil in daily clinical practice. Neurologic toxicity during a treatment with fluoropyrimidines, as 5-fluorouracil, represents a well-known side-effect, largely described in literature. Central nervous system (CNS) toxicity, mainly encephalopathy with or without seizures, occurs occasionally even when conventional doses are used. CNS toxicity incidence increases markedly when the blood-brain barrier is either overwhelmed or bypassed (Hildebrand J. Neurological complications of cancer chemotherapy. Curr Opin Oncol 2006; 18: 321-324). Peripheral nervous system (PNS) toxicity is more common because proximal and distal extremities of the peripheral nerves are not protected by a blood-brain like barrier and peripheral neuropathy remains a major limiting factor for the administration of conventional doses of several agents (Saif W, Wood TE, McGee PJ and Diasio RB. Peripheral neuropathy associated with capecitabine, Anticancer Drugs 2004;15: 767-771). Capecitabine is a prodrug of 5-fluorouracil, more easily administered by mouth; its transformation in 5-fluorouracil is performed in the liver. There are only a few reports on the toxic neurological side-effects of capecitabine. We describe in our report a rare case of toxic encephalopathy in a 82-year-old female, with a brief review of literature. In the literature reviewed, we found 12 neurologic episodes due to capecitabine lasting between a few days till some months. All clinical symptoms of the cases described in literature, obtained a complete regression with the discontinuation of capecitabine. A relation was not found with dihydropyrimidine dehydrogenase (DPD) mutation, also if pharmacologic and pharmacogenetic assessment should be done for this drug, especially in old patients. Toxic encephalopathy represents a rare event during capecitabine treatment and on the bases of the data found, is fairly managed in the clinical setting. The knowledge of the natural history of the toxic effect allows the use of the drug also in old patients.

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.

Small cell neuroendocrine tumor of the breast in a 40 year-old woman: a case report.

INTRODUCTION: Small cell neuroendocrine cancer of the breast is a rare tumor with less than 30 cases reported in the literature. The morphological and immunohistochemical patterns of this tumor are similar to small cell neuroendocrine cancer of the lung. For this reason, it is often difficult to distinguish a primary small cell neuroendocrine cancer of the breast from a metastatic lesion from other sites. CASE PRESENTATION: We report and characterize with immunohistochemical techniques a case of primary small cell neuroendocrine cancer of the breast occurring in a 40-year-old Caucasian woman. A palpable and mobile 3.0 cm tumor was located in the upper-outer quadrant of her right breast. Lumpectomy and subsequent radical mastectomy with axillary lymph node resection were performed. Microscopically, the tumor consisted predominantly of a diffuse proliferation of small oat cells. The tumor cells were positive for neuroendocrine markers chromogranin A and synaptophysin. One of 16 lymph nodes was metastatic. A correct treatment needs to be chosen. CONCLUSIONS: It has recently been demonstrated that early small cell neuroendocrine cancer of the breast shows a good prognosis with adjuvant treatments with high disease free survival. Our patient is alive and well without disease eight years after treatment. We performed an adjuvant therapy with the classic scheme doxorubicin and cyclophosphamide, followed by carboplatin and etoposide. A more extensive review is required to define a standard treatment protocol for this rare neoplasm.

[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.