From codeine to transdermal fentanyl for cancer pain control: a safety and efficacy clinical trial.

BACKGROUND: Fentanyl is a synthetic opioid, suitable for transdermal delivery, offering an interesting solution as a step 3 opioid in cancer pain treatment. The purpose of the study was to carefully investigate: 1) the feasibility of the direct conversion from codeine to TTS fentanyl, in patients already receiving codeine and requiring strong opioids for their analgesia; 2) the safety of 25 microg/hour incremental steps and at shorter than 72-hour intervals, if clinically required. PATIENTS AND METHODS: 130 patients were judged eligible for the study. All the patients were receiving 280-360 mg or more of codeine and required strong opioid for their analgesia. The study lasted 56 days. The initial dose was 25 microg/hour. TTS fentanyl for all patients. Data assessments were made on baseline, day 1, day 2, day 3, in the hospital and thereafter on days 7, 14, 21, 28, 42 and 56. After the patch application, all the patients were given an immediate release oral morphine (5 mg) every 4-6 hours for the first 12 hours and then if needed only as rescue doses. The patients remained in the hospital for the first three days of the study where follow-up (pain score, satisfaction, side effects etc.). was recorded by the palliative care team and by daily cards. RESULTS: The itnitial dose of fentanyl was 25 microg/hour while the mean dose on day 3 was 45.9 microg/hour. All the patients required upward titration of the study medication during follow-up visits. On day 56 the mean dose of fentanyl was 87.4 microg/hour. Mean pain intensity decreased from an initial 5.96 on the baseline to 0.83 on day 3. Karnofsky scale measurements between treatment phases revealed non-significant changes. The rate of overall satisfaction was quite high. Nine patients discontinued the study due to inadequate pain relief or side effects between day 7 and day 28, while five patients died between day 28 and day 56. Constipation, nausea and vomiting were the most common side effects. Skin reaction was relatively mild and acceptable during the study. CONCLUSION: Under controlled conditions, TTS fentanyl seems to be feasible for direct conversion from mild to strong opioids and additionally, 25 microg/hour incremental steps day by day can be made by palliative care specialists, if clinically required for cancer pain management.

Greek brief pain inventory: validation and utility in cancer pain.

OBJECTIVE: The Brief Pain Inventory (BPI) is a pain assessment tool. It has been translated into and validated in several languages. The purpose of this study was the translation into and validation of the BPI in Greek. Moreover, we wanted to detect cultural and social differences, if any, of pain interference in patients' lives. METHODS: The translation and validation of the inventory took place at the Areteion Hospital. The final validation sample consisted of 220 cancer patients (123 males, 97 females, age range 21-87 years, mean age 61.3). Primary cancer locations were lung 25.6%, gastrointestinal tract 25.6%, breast 11.5%, prostate 7.07%, gynecological cancers 9.6% and others 20.57%. The patients themselves completed the majority of the Greek BPI (G-BPI) papers. The pain management index (PMI) was also calculated in order to assess the adequacy of pain treatment. Assessing the reliability and the validity made the actual validation of the G-BPI. RESULTS: Pain severity and pain management: 147 patients reported severe pain, 48 patients moderate, and 25 patients mild pain (mean average pain 6.22). From these patients only 21 were found on strong and 33 on weak opioid treatment, while 166 patients were found on no opioid analgesic treatment. In agreement with these data is the PMI which was positive only for 9 patients, while 44 patients had PMI = 0 and all the others had negative PMI scores. Reliability and Validity of the G-BPI: Coefficient alphas were 0.849 for the interference items and 0.887 for the severity items. Additionally, the factor analysis of the G-BPI items results in a two-factor solution, that satisfies the criteria of reproducibility, interpretability and confirmatory setting. CONCLUSION: This study shows the efficacy of the G-BPI for the assessment of pain severity as well as the pain management in Greece, and therefore its utility in improving the analgesic treatment outcome in Greek patients.

Continuous subcutaneous octreotide in gastrointestinal cancer patients: pain control and beta-endorphin levels.

BACKGROUND: Somatostatin is a naturally occurring hormone widely identified in a number of human tissues, with a broad spectrum of physiological actions. Octreotide is a synthetic analogue of somatostatin, which seems to be promising in clinical use. AIMS: a. to evaluate the efficacy of octreotide in pain control of patients with advanced gastrointestinal cancer, as well as octreotide's outcome in the hepatic function; b. to investigate the relationship between pain intensity and beta-endorphin blood levels in the patients. PATIENTS: The study group consisted of 25 patients (age range: 48-89 years, 14 males, 11 females) with far advanced gastrointestinal cancer. METHODS: All the patients were under s.c. morphine administration using a continuous infusion pump. When pain intensity increased, 0.6 mg/day of octreotide was added to the therapeutic regimen in the same syringe of the continuous infusion pump. Pain intensity and beta-endorphin blood levels were measured five times: Once before octreotide administration and the other four 12, 24, 48 hours and 7 days after. A complete blood count and a biochemical screening profile were taken before the administration of octreotide as well as on the 7th and the 14th day. RESULTS: 24 out of 25 cases showed a reduction in pain intensity (pretreatment x = 5.3, post-treatment x = 0.6). beta-endorphin blood levels increased significantly during the study (an increase of 184.78% was observed on the 7th treatment day). In one patient pain control was achieved by increasing morphine dosage. Statistically significant changes were observed in hepatic function indices (p < 0.02). Significant side-effects were not observed. CONCLUSION: Octreotide can be used as an adjuvant analgesic in the management of gastrointestinal cancer pain which is managed by continuous s.c. administration. Although fuither research needs to be done, octreotide's administration seemed to improve hepatic function of these patients, therefore, it could potentially have a positive effect in the patient's quality of life.

Continuous subcutaneous administration of high-dose salmon calcitonin in bone metastasis: pain control and beta-endorphin plasma levels.

This prospective nonrandomized trial was performed to evaluate the efficacy of salmon calcitonin (sCT) in controlling pain related to bone metastasis in cancer patients and the relation of sCT's analgesic efficacy with beta-endorphin blood levels. The study group consisted of 22 cancer patients with bone metastases (male 13 and female 9, age range 38-77 years). Pain control was first achieved by continuous subcutaneous (s.c.) morphine administration. The next increase in pain was managed with continuous s.c. administration of 400 IU/day sCT. Beta-endorphin blood levels were measured before and during sCT administration. The first measurement was taken before sCT administration; subsequent measurement occurred at 12, 24, and 48 hours and 7 days after the commencement of treatment. Pain scores were monitored by a visual analogue scale. A complete blood count and a biochemical screening profile were taken before the administration of calcitonin and also on the seventh and the fifteenth day of the administration. The results showed a satisfactory analgesic effect. The mean pain score before the calcitonin administration was 4.43 and the score on the seventh day was 1.17. The gradual reduction of pain score was associated with an increase in beta-endorphin blood levels (increase to 147.2% of baseline on the seventh treatment day). In three cases, no satisfactory analgesic effect was obtained and pain control was achieved by increasing the continuous s.c. morphine dosage. No significant side effects were observed. These data suggest that sCT in high doses may be a useful adjuvant analgesic when combined with low doses of morphine in continuous s.c. administration for the management of metastatic bone pain.

Optimizing hospital-based home care for dying cancer patients: a population-based study.

Health-related quality of life (HRQL) is difficult to define and measure. It is a generic term that includes concepts such as physical health, life satisfaction, psychological well-being and self-integrity. Realizing and appreciating the importance of HRQL is crucial for physicians if they are to be in a position to offer appropriate suggestions in assisting patients and their families in the decision-making process regarding cancer treatment and terminal care. In order to determine whether Greek physicians take into consideration HRQL when assessing different therapeutic options, we conducted a postal survey. A total of 1500 Greek physicians (internists, oncologists and anaesthesiologists) were asked to complete a questionnaire. We received replies from 1280 (85%). In summary, we found that Greek physicians: (1) have already started taking HRQL into consideration when reviewing their therapeutic options; (2) increasingly include HRQL in research studies as an outcome measure; (3) do not yet have thoroughly sufficient training in the holistic care of cancer patients and their families; (4) mostly do not have the opportunity to work in interdisciplinary therapeutic teams where they can exchange ideas and consider different aspects of alternative therapeutic methods. It is concluded that HRQL has already been introduced as an important determinant of therapeutic choices in cancer care in Greece. However, efforts need to be made to allow HRQL to enjoy its appropriate place in cancer care.

Comparison of the efficacy and safety of tropisetron, metoclopramide, and chlorpromazine in the treatment of emesis associated with far advanced cancer.

BACKGROUND: A single institution, prospective, randomized trial was performed in terminal cancer patients to compare tropisetron (TRO), metoclopramide (MET), and chlorpromazine (CHL) in the management of nausea and emesis. Patients had far advanced cancer, were far removed from chemotherapy or radiotherapy, and their nausea and emesis was not due to bowel obstruction, drug intake, or cranial, electrolytic, or metabolic causes. The effects of antiemetic treatments were evaluated from Days 1-15. METHODS: Two hundred and eighty patients were randomized to receive 1) MET+ dexamethasone (DEX) (10 mg*4 and 2 mg*1, respectively, orally), 2) TRO (5 mg*1, orally), 3) TRO + MET (5 mg*1 and 10 mg*2, respectively, orally), 4) TRO + MET + DEX (5 mg*1, 10 mg*2, and 2 mg*1, respectively, orally), 5) CHL + DEX (25 mg*2 and 2 mg*1, respectively, orally), 6) TRO + CHL (5 mg*1 and 12.5 mg*2, respectively, orally), or 7) TRO + CHL + DEX (5 mg*1, 12.5 mg*2, and 2 mg*1, respectively, orally). Total control was defined as no nausea or emesis. RESULTS: By the end of the 15th day, total control of emesis was obtained in 23.6% (9 of 38) of MET + DEX patients, 78.9% (30 of 38) of TRO patients, 84.2% (32 of 38) of TRO + MET patients, 92.3% (36 of 39) of TRO + MET + DEX patients, 33.3 (13 of 39) of CHL + DEX patients, 84.6% (33 of 39) of TRO + CHL patients, and 92.5% (37 of 40) of TRO + CHL + DEX patients. Total control of nausea was achieved in 18.4% (7 of 38) of MET + DEX patients, 65.7% (25 of 38) of TRO patients, 73.6% (28 of 38) of TRO + MET patients, 87.1% (34 of 39) of TRO + MET + DEX patients, 17.9% (7 of 39) of CHL + DEX patients, 74.3% (29 of 39) of TRO + CHL patients, and 85% (34 of 40) of TRO + CHL + DEX patients. When comparing MET + DEX versus TRO; MET + DEX versus TRO + MET; MET + DEX versus TRO + MET + DEX; MET + DEX versus TRO + CHL; MET + DEX versus TRO + CHL + DEX; CHL + DEX versus TRO; CHL + DEX versus TRO + MET; CHL + DEX versus TRO + MET + DEX; CHL + DEX versus TRO + CHL; and CHL + DEX versus TRO + CHL + DEX, significant differences were noted. All antiemetic drugs were well tolerated with no severe side effects observed in any treatment arm. CONCLUSIONS: These data suggest that 5-HT3 receptor antagonists such as tropisetron clinically are more effective in the control of emesis of patients with far advanced cancer than previously used agents. This study raises important issues when attempting to decide which antiemetic therapy to choose for an individual patient with far advanced disease.

Comparison of tropisetron and chlorpromazine combinations in the control of nausea and vomiting of patients with advanced cancer.

The single-institution, prospective, randomized trial was performed to evaluate the efficacy of tropisetron and chlorpromazine in the management of nausea and vomiting of terminal cancer patients. Patients had no recent chemotherapy or radiotherapy, and emesis was not due to bowel obstruction, electrolytic or metabolic disturbances, drug intake, or intracranial disease. One hundred and sixty patients randomly received either (a) chlorpromazine (CLO) (50 mg/day) plus dexamethasone (DEX) (2 mg/day), (b) chlorpromazine (25 mg/day) plus tropisetron (TRO) (5 mg/day), (c) chlorpromazine (25 mg/day plus tropisetron (5 mg/day) plus dexamethasone (2 mg/day), or (d) tropisetron (TRO) (5 mg/day). Patients were monitored from day 1 to day 15. No nausea or vomiting was defined as "total" control. On day 15, total vomiting control was achieved in 33.3% of the patients receiving CLO + DEX, 84.6% of the patients receiving CLO + TRO, 92.5% of the patients receiving CLO + TRO + DEX, and 78.9% of the patients receiving TRO. Total control of nausea was achieved in 18.0% of the patients receiving CLO + DEX, 74.4% of the patients receiving (CLO + TRO), 85.0% of the patients receiving CLO + TRO + DEX, and 65.8% of the patients receiving TRO. Tropisetron-containing combinations produced significant control of nausea and vomiting from the third day onward. All antiemetic drugs were well tolerated. These data suggest that tropisetron-containing combinations or tropisetron as a single agent are much more effective in the control of emesis in patients with advanced cancer than the conventional antiemetic combination of chlorpromazine plus dexamethasone. Tropisetron is well tolerated and may be the best choice for controlling persistent nausea and vomiting in terminal cancer patients.

Tropisetron versus Metoclopramide in the Control of Emesis in Far-Advanced Cancer.

The present study was conducted to assess the optimum treatment for nausea and vomiting in patients with far advanced cancer. More specifically, we studied patients with cancers that were too far advanced to benefit from chemotherapy or radiotherapy and whose nausea and vomiting were not due to drug intake, cranial, electrolytic, or metabolic causes. One hundred twenty patients who were under antiemetic medication with metoclopramide (MET) and suddenly presented with uncontrolled nausea and vomiting were randomized to three different therapeutic regimens: MET plus dexamethasone (DEX), MET plus tropisetron (TRO), and MET plus TRO plus DEX. Patient diary cards were used to assess nausea and vomiting. By the end of day 15, total control of vomiting was achieved in 24% of MET plus DEX patients, in 84% of MET plus TRO patients, and in 92% of MET plus TRO plus DEX patients. Total control of nausea was achieved in 18% of MET plus DEX patients, in 74% of MET plus TRO patients, and in 87% of MET plus TRO plus DEX patients. All antiemetic treatments were similarly well tolerated. TRO in combination with either MET or MET and DEX produced the best control of both nausea and vomiting.