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Pemetrexed improves survival in mesothelioma
Newsdesk Pemetrexed improves survival in mesothelioma Encouraging results have emerged from the largest trial to investigate the effects of chemotherapy in malignant pleural mesothelioma (MPM), which was discussed at the annual meeting of the American Society of Clinical Oncology (May 18–21, 2002, FL, USA). The phase III international trial investigated the efficacy of pemetrexed (Alimta)—a novel antifolate drug that targets three key enzymes in purine and pyrimidine synthesis. Substantially improved lung function was reported, which became apparent by the second cycle of treatment. 456 patients with pleural mesothelioma who were not suitable for surgery and had not received any chemotherapy were randomly assigned to receive pemetrexed (500 mg/m2) followed by cisplatin (75 mg/m2), or cisplatin plus saline. After only 150
patients had been recruited to the study, alarming rates of severe toxicity and death were observed in the pemetrexed-treated group. Since these side-effects were associated with increased homocysteine all patients recruited subsequently were given folic acid and vitamin B12, in addition to the experimental treatment. Pemetrexed caused a significant increase in survival, from a median of 9·3 months (cisplatin with saline) to 12·1 months (pemetrexed plus cisplatin). Patients who received folic acid and vitamin B12 supplementation for the entire study had even higher median survival: 10·0 months and 13·3 months, respectively. Tumour response was also greater with pemetrexed (41% versus 17%). Lead investigator Nicholas Vogelzang (University of Chicago, IL, USA) says: “Patients with mesothelioma and
their families now have proof that pemetrexed offers real and tangible benefits.” Valerie Rusch (Memorial SloanKettering Cancer Center, NY, USA) was enthusiatic about the results, “The pathogenesis of mesothelioma has been poorly understood and there has previously been a nihilistic approach to its treatment.” She explained why the trial is an important step forward: “It included patients typical of the overall patient population, so the results are generalisable to oncology practice at large.” Vogelzang and Rusch agree that pemetrexed plus cisplatin should be adopted as standard treatments for MPM. New trials should “explore the effects of pemetrexate in combination with other cytotoxic agents and targeted therapies,” adds Rusch. Susan Mayor
Researchers recommend early use of implantable drug pump
386
At 4 weeks, the mean pain score of patients who received the pump was 51·5% lower than at the start of the study, whereas the other group had a 39·1% pain-score reduction. Mean drug toxicity was reduced by 50·3% and 17·1%, respectively. For both endpoints, there was a significant difference The pump, about the size of a hockey puck, is surgically implanted into the abdomen and connected to a catheter between the groups. that leads to the intrathecal space. Moreover, there was a greater reduction in opioid side-effects (Harvard University, MA, USA). “The in the pump group compared with the survival data are suggestive, but cannot control group. be relied upon as being accurate Survival was not a planned end- because survival was not a primary or point of the study, but the researchers secondary endpoint of the trial,” he noted that the pump conferred a sur- warns. vival benefit; 53·9% of patients in the “It is important to rethink how we pump group were alive at 6 months, care for people who are persistently or compared with 37·2% of patients in the chronically uncomfortable,” Schnipper control group. “That’s better than emphasises. “The observation about many chemotherapies offer for diseases survival is really interesting, and I like pancreatic cancer,” Staats adds. believe it’s important enough to The study data about analgesia and generate a hypothesis and design a toxicity are “quite convincing”, proper clinical trial to test it.” according to Lowell Schnipper Faith Reidenbach
Courtesy of Medtronic, Inc.
For control of refractory cancer pain, implantation of an intrathecal drug pump is better than conventional management, according to the results of a prospective, randomised trial. “There needs to be a paradigm shift in how we think about patient care at the end of life”, says co-principal investigator Peter Staats (Johns Hopkins Medical Institute, MD, USA). “The old paradigm was to give patients narcotics until they became toxic. What this study showed was that if oncologists intervene early, by implanting a device, not only will they avoid dose escalation of systemic drugs, they’ll also minimise toxicity.” Staats and colleagues looked at 202 cancer patients at 21 centres who were refractory to 200 mg/day morphine, or the oral equivalent, or who experienced intolerable side-effects with lower doses. The patients were given conventional treatments with or without implantation of an externally programmable drug pump. The study was funded by Medtronic, which markets the pump under the name SynchroMed.
THE LANCET Oncology Vol 3 July 2002
http://oncology.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
patients had been recruited to the study, alarming rates of severe toxicity and death were observed in the pemetrexed-treated group. Since these side-effects were associated with increased homocysteine all patients recruited subsequently were given folic acid and vitamin B12, in addition to the experimental treatment. Pemetrexed caused a significant increase in survival, from a median of 9·3 months (cisplatin with saline) to 12·1 months (pemetrexed plus cisplatin). Patients who received folic acid and vitamin B12 supplementation for the entire study had even higher median survival: 10·0 months and 13·3 months, respectively. Tumour response was also greater with pemetrexed (41% versus 17%). Lead investigator Nicholas Vogelzang (University of Chicago, IL, USA) says: “Patients with mesothelioma and
their families now have proof that pemetrexed offers real and tangible benefits.” Valerie Rusch (Memorial SloanKettering Cancer Center, NY, USA) was enthusiatic about the results, “The pathogenesis of mesothelioma has been poorly understood and there has previously been a nihilistic approach to its treatment.” She explained why the trial is an important step forward: “It included patients typical of the overall patient population, so the results are generalisable to oncology practice at large.” Vogelzang and Rusch agree that pemetrexed plus cisplatin should be adopted as standard treatments for MPM. New trials should “explore the effects of pemetrexate in combination with other cytotoxic agents and targeted therapies,” adds Rusch. Susan Mayor
Researchers recommend early use of implantable drug pump
386
At 4 weeks, the mean pain score of patients who received the pump was 51·5% lower than at the start of the study, whereas the other group had a 39·1% pain-score reduction. Mean drug toxicity was reduced by 50·3% and 17·1%, respectively. For both endpoints, there was a significant difference The pump, about the size of a hockey puck, is surgically implanted into the abdomen and connected to a catheter between the groups. that leads to the intrathecal space. Moreover, there was a greater reduction in opioid side-effects (Harvard University, MA, USA). “The in the pump group compared with the survival data are suggestive, but cannot control group. be relied upon as being accurate Survival was not a planned end- because survival was not a primary or point of the study, but the researchers secondary endpoint of the trial,” he noted that the pump conferred a sur- warns. vival benefit; 53·9% of patients in the “It is important to rethink how we pump group were alive at 6 months, care for people who are persistently or compared with 37·2% of patients in the chronically uncomfortable,” Schnipper control group. “That’s better than emphasises. “The observation about many chemotherapies offer for diseases survival is really interesting, and I like pancreatic cancer,” Staats adds. believe it’s important enough to The study data about analgesia and generate a hypothesis and design a toxicity are “quite convincing”, proper clinical trial to test it.” according to Lowell Schnipper Faith Reidenbach
Courtesy of Medtronic, Inc.
For control of refractory cancer pain, implantation of an intrathecal drug pump is better than conventional management, according to the results of a prospective, randomised trial. “There needs to be a paradigm shift in how we think about patient care at the end of life”, says co-principal investigator Peter Staats (Johns Hopkins Medical Institute, MD, USA). “The old paradigm was to give patients narcotics until they became toxic. What this study showed was that if oncologists intervene early, by implanting a device, not only will they avoid dose escalation of systemic drugs, they’ll also minimise toxicity.” Staats and colleagues looked at 202 cancer patients at 21 centres who were refractory to 200 mg/day morphine, or the oral equivalent, or who experienced intolerable side-effects with lower doses. The patients were given conventional treatments with or without implantation of an externally programmable drug pump. The study was funded by Medtronic, which markets the pump under the name SynchroMed.
THE LANCET Oncology Vol 3 July 2002
http://oncology.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.