Front-line treatment of advanced non-small-cell lung cancer with MTA (LY231514, Pemetrexed disodium, ALIMTA™ and cisplatin: A multicenter phase II trial

Abstract

MTA plus cisplatin is well tolerated and active against NSCLC. Further studies of this combination are warranted.

Phase II study of pemetrexed in combination with carboplatin in the first‐line treatment of advanced nonsmall cell lung cancer

“…11,12 Furthermore, the Phase II study randomizing patients to pemetrexed plus either carboplatin or oxaliplatin had median survivals of 9.9 and 9.3 months, respectively (although with response rates similar to those in the trial reported here-31.6% and 26.8%). 26 In addition, compared with the 1-year and median survivals (12.2-14.2 mos and 52-62%, respectively) in 4 Phase II outcomes of representative platinum doublets including cisplatin or carboplatin plus gemcitabine, carboplatin plus paclitaxel, and carboplatin plus docetaxel, there is comparable activity.…”

“…21 The addition of vitamin prophylaxis was shown to reduce both homocysteine and methylmelonic acid levels and significantly reduce toxicity in patients treated with pemetrexed. 22 These results were confirmed by a Phase III study in malignant pleural mesothelioma showing a clear improvement in the tolerability of pemetrexed and no compromise of efficacy or survival with the addition of vitamin B 12 prophylaxis. 14 In addition to receiving folic acid and vitamin B 12 prophylaxis, patients in our study were premedicated with dexamethasone, as ear- lier studies had found that such prophylaxis reduced the incidence of Grade 3 rash.…”

“…22 These results were confirmed by a Phase III study in malignant pleural mesothelioma showing a clear improvement in the tolerability of pemetrexed and no compromise of efficacy or survival with the addition of vitamin B 12 prophylaxis. 14 In addition to receiving folic acid and vitamin B 12 prophylaxis, patients in our study were premedicated with dexamethasone, as ear- lier studies had found that such prophylaxis reduced the incidence of Grade 3 rash. 9,10 In the study reported here, we evaluated whether replacing cisplatin with carboplatin and adding vitamin prophylaxis would maintain the efficacy of the original pemetrexed-cisplatin combination while improving tolerability.…”

“…The median number of chemotherapy cycles administered was 6 (range, [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. No patients are still receiving the doublet, although at the time of this writing two patients are continuing on single-agent pemetrexed.…”

“…8 In two single-agent Phase II studies, one from Canada and the other from Australia, pemetrexed as first-line treatment for advanced NSCLC produced overall response rates of 23.3% (95% confidence interval [CI]: 9.9 -42.3%) and 15.8% (95% CI: 7-28%), respectively; median survival of 9.2 months and 7.2 months, respectively; and 1-year survival rates of 25.3% and 32%, respectively. 9,10 Two other Phase II studies, from Canada and Europe, building on the Phase I data for pemetrexed plus cisplatin, examined this combination for first-line treatment of advanced NSCLC 11,12 (Table 1). Response rates were 38.9% in the European trial and 44.8% in the Canadian trial; median survival and the 1-year survival rate were 10.9 months and 50% in the European trial and 8.9 months and 49% in the Canadian trial.…”