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Alimta/Platinum Doublets Studied for Palliative Care of Advanced NSCLC

Alimta/Platinum Doublets Studied for Palliative Care of Advanced NSCLC

NEW YORK-Doublets of pemetrexed (Alimta) and a platinum may provide a better therapeutic index than standard regimens for palliative treatment of non-small-cell lung cancer (NSCLC), Giorgio V. Scagliotti, MD, said at the Chemotherapy Foundation Symposium XXII (abstract 65). In a multicenter, randomized phase II study, the median survival for pemetrexed/carboplatin (Paraplatin) and pemetrexed/ oxaliplatin (Eloxatin) was 10.5 months, while objective response rates were in the range of 30%, comparable with "any other platinum-based doublets currently available" for treatment of unresectable, locally advanced, or metastatic NSCLC, he said. In addition, the amount of grade 3-4 hematologic and nonhematologic toxicity is "very low," compared with earlier studies of doublets in NSCLC. "Both regimens appeared to provide a favorable risk-benefit profile, and warrant additional investigation in the phase III setting," said Dr. Scagliotti, of S. Luigi Gonzaga Hospital, University of Torino (Turin), Italy. In Europe, future clinical development will likely focus on the pemetrexed/carboplatin doublet. "My personal opinion is we need to set up a study showing that carboplatin/ Alimta is not inferior to cisplatin/ Alimta, if we want to get off of this boring story of carboplatin vs cisplatin," Dr. Scagliotti commented. Pemetrexed, a novel antifolate, is approved in the United States for second- line treatment of NSCLC and first-line treatment of malignant pleural mesothelioma. Front-line use of pemetrexed plus a platinum in NSCLC was the subject of this study and a separate 50-patient phase II trial conducted by MD. Anderson Cancer Center investigators. Early studies of pemetrexed and platinum have yielded encouraging results, including a response rate of 32% in malignant pleural mesothelioma (Hughes et al: J Clin Oncol 16:3533-3544, 2002). In addition, a phase I investigation of pemetrexed/ oxaliplatin in patients with advanced solid tumors found the doublet was well-tolerated, with neutropenia being the main toxicity observed (Gamelin et al: ASCO 2000, abstract 867). Study and Results Accordingly, Dr. Scagliotti and his coinvestigators enrolled chemotherapy- naive patients with unresectable, locally advanced, or metastatic NSCLC to one of two treatment regimens: pemetrexed 500 mg/m2 plus carboplatin IV infusion to an AUC of 6 (n = 39) or pemetrexed 500 mg/m2 plus oxaliplatin 120 mg/m2 IV infusion (n = 41). Histologic subtype was adenocarcinoma in most patients (41% for the pemetrexed/carboplatin arm; 58.5% for pemetrexed/ oxaliplatin), and a little more than 60% of patients in both groups had stage IV disease. The objective response rate was 31.6% in the pemetrexed/carboplatin arm and 26.8% in the pemetrexed/ oxaliplatin arm; median survival was 10.5 months in both arms. "The median survival times we saw in this study are comparable with the data from phase II and III clinical trials we did in the past," Dr. Scagliotti said. The MD. Anderson phase II study of pemetrexed/carboplatin, which enrolled 50 mostly stage IV NSCLC patients, had a similar objective response rate-about 30%-and an overall survival "slightly better than in our experience," he said. Grade 3-4 hematologic toxicity in Dr. Scagliotti's study was "surprisingly .... extremely low," he said, compared with studies of other doublets. Neutropenia occurred in 25.6% with pemetrexed/carboplatin and 7.3% with pemetrexed/oxaliplatin, while thrombocytopenia was seen in 17.9% and 2.4%, respectively; anemia in 7.7% and 2.4%; and febrile neutropenia in 5.2% and 2.4%. Nonhematologic grade 3-4 toxicity was "really minimal" in both arms. There were a few cases of fatigue and vomiting, and stomatitis, sensory neuropathy, and diarrhea in one patient each. Results of the study described by Dr. Scagliotti were published in the January 2005 issue of Clinical Cancer Research.

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