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Methadone safe and effective for treating cancer pain
Newsdesk
Relapsed Epstein-Barr virus (EBV)positive Hodgkin’s disease does respond to antiviral T-cells, according to research reported at the Fifth International AIDS Malignancy Conference (Bethesda, Maryland, USA) in April. In a preliminary dose escalation trial, Cliona Rooney, Helen Heslop, and colleagues (Baylor College of Medicine, Houston, USA), observed mixed responses in 11 patients with Hodgkin’s disease treated with infusions of EBV-specific, cytotoxic T lymphocytes (CTLs). “Tumour responses were seen at some sites in some cases, and three patients remain stable after 10 months of therapy”, says Rooney. “Three of three patients who received CTLs as adjuvant therapy after autologous stem-cell rescue remain in remission. Three of eight who were treated in relapse had stable disease for one year”, she explains. When the immune system recognises and destroys foreign cells, some cancers are nipped in the bud. However, many slow-growing cancers, such as the immunoblastic lymphoma, Hodgkin’s disease, escape this surveillence, by producing molecules which inhibit the cytotoxic response, or by not expressing enough immunogenic protein to be recognised. One way to overcome this is to take T-cells from individual patients, activate them in vitro by presenting them with cancer-derived proteins, and expanding these populations in culture. About half of patients with Hodgkin’s disease carry EBV genomes and express EBV proteins, so viral proteins are candidate targets for immunotherapy in these cases. When Rooney and colleagues followed this approach using proteins expressed in Hodgkin’s disease, and re-infused the CTLs, they were able to control the virally-infected normal B cells, decreasing viral load in the peripheral blood, and increasing immunity to EBV proteins expressed in tumour cells. Using in situ PCR for marker sequences, they also saw homing of the CTLs to tumour tissues, and infiltration of diseased THE LANCET Oncology Vol 2 June 2001
© John Sixbey
Immunotherapy shows promise in Hodgkin’s disease
In situ hybridisation showing cytotoxic T lymphocytes in a mediastinal tumour from a patient with relapsed Hodgkin’s disease, 2 months after CTL infusion
nodes. “We are overcoming the relatively limited potential of patients’ cells to expand by improving culture media and using feeder cells”, explains Rooney, “and we can now generate CTLs in only 10–16 weeks”.
Hodgkin’s disease frequently arises as a complication of AIDS, and generation of EBV-specific CTLs may offer a way to treat such patients. However, on its own it may not be sufficient to provide a cure. Other work is underway, including generation of T cells expressing a mutant transforming growth factor receptor. “These T cells may provide resistance to this immune inhibitory cytokine and overcome inhibition of the immune response”, says Rooney, “and we intend to overcome more of the tumour-mediated immune evasion strategies, so we can provide a reproducible, effective treatment for Hodgkin’s disease”. Janet Stephenson
Methadone safe and effective for treating cancer pain When Juan Santiago-Palma suggests to his chronic cancer pain patients that he wants to switch them from fentanyl to methadone, there is almost always resistance. “I’m not a drug addict”, they tell him, “isn’t that what junkies take?” Despite the notoriety associated with methadone, Santiago-Palma, a pain and palliative care Fellow at Memorial Sloan-Kettering Cancer Center (New York, USA) says methadone is receiving renewed attention from clinicians who treat chronic and severe pain. “If the patients don’t raise their eyebrows, then members of their family will say something”, said Craig Kornick, also at Memorial Sloan-Kettering. “But methadone works very well to control pain”, he told the 20th annual scientific meeting of the American Pain Society in Phoenix, Arizona, USA, in April. “Methadone is making a comeback”, says Richard DuBose, Medical Director of the Idaho Pain Center, Boise, USA. “It is evident by the interest shown in presentations at this meeting. And there are good reasons that methadone should be used more in chronic pain cases. It is long-lasting, effective in controlling
pain, and it is cheap”. Santiago-Palma and Kornick are among the authors of a study conducted at Memorial SloanKettering, in which patients who were experiencing sedation and confusion on intravenous fentanyl were switched to methadone. Confusion scores among the 25 cancer patients on intravenous fentanyl averaged around 1.5 on a scale of 0–3. When switched to methadone, the scores fell to 0.16 on the first day, and 0.44 on the fourth day of treatment. SantiagoPalma said the difference in the scores was statistically significant (p=0001). Pain scores were also significantly decreased after patients were stabilised on intravenous methadone. The mean pain score decreased from 8.1 (range 5–10) before the switch, to 4.8 (range 1–10) on the day after the switch, and to 3.22 (range 1–6) on the fourth day after the switch. “We believe that the use of intravenous patient-controlled analgesia using methadone is safe and effective in the treatment of cancer pain”, says Santiago-Palma. Edward Susman
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For personal use. Only reproduce with permission from The Lancet Publishing Group.
Relapsed Epstein-Barr virus (EBV)positive Hodgkin’s disease does respond to antiviral T-cells, according to research reported at the Fifth International AIDS Malignancy Conference (Bethesda, Maryland, USA) in April. In a preliminary dose escalation trial, Cliona Rooney, Helen Heslop, and colleagues (Baylor College of Medicine, Houston, USA), observed mixed responses in 11 patients with Hodgkin’s disease treated with infusions of EBV-specific, cytotoxic T lymphocytes (CTLs). “Tumour responses were seen at some sites in some cases, and three patients remain stable after 10 months of therapy”, says Rooney. “Three of three patients who received CTLs as adjuvant therapy after autologous stem-cell rescue remain in remission. Three of eight who were treated in relapse had stable disease for one year”, she explains. When the immune system recognises and destroys foreign cells, some cancers are nipped in the bud. However, many slow-growing cancers, such as the immunoblastic lymphoma, Hodgkin’s disease, escape this surveillence, by producing molecules which inhibit the cytotoxic response, or by not expressing enough immunogenic protein to be recognised. One way to overcome this is to take T-cells from individual patients, activate them in vitro by presenting them with cancer-derived proteins, and expanding these populations in culture. About half of patients with Hodgkin’s disease carry EBV genomes and express EBV proteins, so viral proteins are candidate targets for immunotherapy in these cases. When Rooney and colleagues followed this approach using proteins expressed in Hodgkin’s disease, and re-infused the CTLs, they were able to control the virally-infected normal B cells, decreasing viral load in the peripheral blood, and increasing immunity to EBV proteins expressed in tumour cells. Using in situ PCR for marker sequences, they also saw homing of the CTLs to tumour tissues, and infiltration of diseased THE LANCET Oncology Vol 2 June 2001
© John Sixbey
Immunotherapy shows promise in Hodgkin’s disease
In situ hybridisation showing cytotoxic T lymphocytes in a mediastinal tumour from a patient with relapsed Hodgkin’s disease, 2 months after CTL infusion
nodes. “We are overcoming the relatively limited potential of patients’ cells to expand by improving culture media and using feeder cells”, explains Rooney, “and we can now generate CTLs in only 10–16 weeks”.
Hodgkin’s disease frequently arises as a complication of AIDS, and generation of EBV-specific CTLs may offer a way to treat such patients. However, on its own it may not be sufficient to provide a cure. Other work is underway, including generation of T cells expressing a mutant transforming growth factor receptor. “These T cells may provide resistance to this immune inhibitory cytokine and overcome inhibition of the immune response”, says Rooney, “and we intend to overcome more of the tumour-mediated immune evasion strategies, so we can provide a reproducible, effective treatment for Hodgkin’s disease”. Janet Stephenson
Methadone safe and effective for treating cancer pain When Juan Santiago-Palma suggests to his chronic cancer pain patients that he wants to switch them from fentanyl to methadone, there is almost always resistance. “I’m not a drug addict”, they tell him, “isn’t that what junkies take?” Despite the notoriety associated with methadone, Santiago-Palma, a pain and palliative care Fellow at Memorial Sloan-Kettering Cancer Center (New York, USA) says methadone is receiving renewed attention from clinicians who treat chronic and severe pain. “If the patients don’t raise their eyebrows, then members of their family will say something”, said Craig Kornick, also at Memorial Sloan-Kettering. “But methadone works very well to control pain”, he told the 20th annual scientific meeting of the American Pain Society in Phoenix, Arizona, USA, in April. “Methadone is making a comeback”, says Richard DuBose, Medical Director of the Idaho Pain Center, Boise, USA. “It is evident by the interest shown in presentations at this meeting. And there are good reasons that methadone should be used more in chronic pain cases. It is long-lasting, effective in controlling
pain, and it is cheap”. Santiago-Palma and Kornick are among the authors of a study conducted at Memorial SloanKettering, in which patients who were experiencing sedation and confusion on intravenous fentanyl were switched to methadone. Confusion scores among the 25 cancer patients on intravenous fentanyl averaged around 1.5 on a scale of 0–3. When switched to methadone, the scores fell to 0.16 on the first day, and 0.44 on the fourth day of treatment. SantiagoPalma said the difference in the scores was statistically significant (p=0001). Pain scores were also significantly decreased after patients were stabilised on intravenous methadone. The mean pain score decreased from 8.1 (range 5–10) before the switch, to 4.8 (range 1–10) on the day after the switch, and to 3.22 (range 1–6) on the fourth day after the switch. “We believe that the use of intravenous patient-controlled analgesia using methadone is safe and effective in the treatment of cancer pain”, says Santiago-Palma. Edward Susman
329
For personal use. Only reproduce with permission from The Lancet Publishing Group.