Pain, in neoplastic disease, is a symptom with severe negative impact on the quality of life of patients and a high incidence, with values around 70-90% in advanced and metastatic stages. Than 20 years the main reference for the pharmacological treatment of cancer pain are the guidelines produced by the World Health Organization (WHO). This document shows that the use of opioid drugs is the mainstay of treatment, with particular reference to opioids "major" (3 rd step of the analgesic ladder). The 4 opioids more most commonly prescribed in Italy (oral morphine and oxycodone, fentanyl and buprenorphine transdermal), based on the data currently available, have an analgesic effect would partly overlap but with different percentages of non-responders (NR), a different need to increase the dose over time to maintain adequate analgesia, a different action to the switch to another molecule for ineffectiveness analgesic. The observations described suggest that opioids, although they belong to the same family drug may not be fully comparable with regard to the clinical effects products. Important differences are known on the pharmacokinetic and pharmacodynamic and, more recently, also in terms of pharmacogenomics. This is a comparative study of analgesic strategies based on the use of the 4 mentioned opioids, going to look for possible differences in terms of analgesic efficacy, changes in dose over time, use of switch or permanent abandonment of treatment, parallel to the contour of the side effects. The associated sub-project will link the structure gene of patients and clinical results have emerged.

Inclusion Criteria:

• patients with diagnostic (histological or cytological) evidence of locally advanced or metastatic solid tumour;
• with average pain intensity ≥ 4, measured with NRS and related to the last 24 hours, due to the cancer, requiring for the first time an analgesic treatment with 3rd step/WHO opioids
• with life expectancy > one month
• "strong" opioid naïve;
• eligible to take any of the medications under evaluation, by TDS or by mouth;
• with age ≥ 18 years;

Exclusion Criteria:

• Patients recruited in other researches that conflict or may confound the conduction and results of the present study;
• Lack of informed consent;
• with presence of other diseases, including psychiatric/mental illness, severe senile or other form of dementia, that can interfere with participation and compliance with the study protocol or can contraindicate the use of the investigational drugs;
• with presence of co-morbidities, which could create potentially dangerous drug interactions with opioids (eg, use of macrolide antibiotics or antifungal,….);
• any kind of contraindications to the use of opioid drugs;
• Patients with a known story, past or current, of drugs abuse or addiction;
• Use of drugs which presents a combination of opioids and other molecule (as NSAIDs, paracetamol, naloxone, ..);
• Patients who cannot guarantee regular follow-up visits for logistic or geographic reasons;
• Need of starting 3rd step treatment in an "emergency clinical situation" that do not allow the correct procedures of randomization;
• diagnosis of primary brain tumor or leukaemia;
• diagnosis of chronic renal failure;
• patients with antalgic radiotherapy or radio-metabolic therapy in progress or completed less than 14 days before study;
• patients starting a first line chemotherapy simultaneously to the beginning of the study;
• other types of analgesic treatments, including local-regional anesthetic techniques or neurosurgical /ablative methods.