RCT Comparing the Analgesic Efficacy of 4 Therapeutic Strategies Based on 4 Different Major Opioids (Fentanyl, Oxycodone, Buprenorphine vs Morphine) in Cancer Patients With Moderate/Severe Pain, at the Moment of Starting 3rd Step of WHO Analgesic Ladder.

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.