Alimta/Platinum Doublets Studied for Palliative Care of Advanced NSCLC

March 1, 2005

This special “annual highlights” supplement to Oncology News International is acompilation of major advances in the management of lung cancer during 2004, asreported in ONI. Guest editor Dr. Roy Herbst discusses these advances in clinicalmanagement, with a focus on developments in adjuvant therapy for early disease,targeted therapy, and new chemotherapy findings.

NEW YORK-Doublets ofpemetrexed (Alimta) and a platinummay provide a better therapeutic indexthan standard regimens for palliativetreatment of non-small-celllung cancer (NSCLC), Giorgio V.Scagliotti, MD, said at the ChemotherapyFoundation Symposium XXII(abstract 65). In a multicenter, randomizedphase II study, the mediansurvival for pemetrexed/carboplatin(Paraplatin) and pemetrexed/oxaliplatin (Eloxatin) was 10.5months, while objective response rateswere in the range of 30%, comparablewith "any other platinum-based doubletscurrently available" for treatmentof unresectable, locally advanced, ormetastatic NSCLC, he said.In addition, the amount of grade3-4 hematologic and nonhematologictoxicity is "very low," compared withearlier studies of doublets in NSCLC."Both regimens appeared to providea favorable risk-benefit profile, andwarrant additional investigation in thephase III setting," said Dr. Scagliotti,of S. Luigi Gonzaga Hospital, Universityof Torino (Turin), Italy.In Europe, future clinical developmentwill likely focus on thepemetrexed/carboplatin doublet. "Mypersonal opinion is we need to set upa study showing that carboplatin/Alimta is not inferior to cisplatin/Alimta, if we want to get off of thisboring story of carboplatin vs cisplatin,"Dr. Scagliotti commented.Pemetrexed, a novel antifolate, isapproved in the United States for second-line treatment of NSCLC andfirst-line treatment of malignant pleuralmesothelioma. Front-line use ofpemetrexed plus a platinum inNSCLC was the subject of this studyand a separate 50-patient phase II trialconducted by MD. Anderson CancerCenter investigators.Early studies of pemetrexed andplatinum have yielded encouragingresults, including a response rate of32% in malignant pleural mesothelioma(Hughes et al: J Clin Oncol16:3533-3544, 2002). In addition, aphase I investigation of pemetrexed/oxaliplatin in patients with advancedsolid tumors found the doublet waswell-tolerated, with neutropenia beingthe main toxicity observed (Gamelinet al: ASCO 2000, abstract 867).Study and ResultsAccordingly, Dr. Scagliotti and hiscoinvestigators enrolled chemotherapy-naive patients with unresectable,locally advanced, or metastaticNSCLC to one of two treatment regimens:pemetrexed 500 mg/m2 pluscarboplatin IV infusion to an AUC of6 (n = 39) or pemetrexed 500 mg/m2plus oxaliplatin 120 mg/m2 IV infusion(n = 41). Histologic subtype wasadenocarcinoma in most patients(41% for the pemetrexed/carboplatinarm; 58.5% for pemetrexed/oxaliplatin), and a little more than60% of patients in both groups hadstage IV disease.The objective response rate was31.6% in the pemetrexed/carboplatinarm and 26.8% in the pemetrexed/oxaliplatin arm; median survival was10.5 months in both arms. "The mediansurvival times we saw in thisstudy are comparable with the datafrom phase II and III clinical trials wedid in the past," Dr. Scagliotti said.The MD. Anderson phase II study ofpemetrexed/carboplatin, which enrolled50 mostly stage IV NSCLC patients,had a similar objective responserate-about 30%-and an overall survival"slightly better than in our experience,"he said.Grade 3-4 hematologic toxicity inDr. Scagliotti's study was "surprisingly.... extremely low," he said, comparedwith studies of other doublets. Neutropeniaoccurred in 25.6% withpemetrexed/carboplatin and 7.3%with pemetrexed/oxaliplatin, whilethrombocytopenia was seen in 17.9%and 2.4%, respectively; anemia in7.7% and 2.4%; and febrile neutropeniain 5.2% and 2.4%. Nonhematologicgrade 3-4 toxicity was "reallyminimal" in both arms. There were afew cases of fatigue and vomiting, andstomatitis, sensory neuropathy, anddiarrhea in one patient each.Results of the study described byDr. Scagliotti were published in theJanuary 2005 issue of Clinical CancerResearch.