Pemetrexed and cisplatin with concurrent radiotherapy for locally advanced non-small cell and limited disease small cell lung cancer: results from 2 phase I studies.

Abstract Background The objectives were to determine the maximum tolerated dose (MTD) of pemetrexed and cisplatin with concurrent radiotherapy. Secondary objectives include incidence and nature of acute and late toxicities, tumor response and overall survival. Patients and methods Treatment naive patients received 1 cycle of cisplatin 80 mg/m 2 in study I (stage III NSCLC), 75 mg/m 2 in study II (LD-SCLC) and pemetrexed 500 mg/m 2 before the phase I part. In study I, patients were treated in cohorts with escalating cisplatin doses (60–80 mg/m 2 ), pemetrexed doses (400–500 mg/m 2 ) and concurrent escalating radiotherapy doses (66 Gy in 33–27 fractions). In study II, patients were treated with cisplatin 75 mg/m 2 and escalating pemetrexed doses (400–500 mg/m 2 ) with concurrent escalating radiotherapy doses (50–62 Gy). Results The trials closed prematurely: study I because of poor accrual, study II because of sponsor decision. Thirteen patients were treated: 4 with NSCLC, 9 with LD-SCLC. No dose-limiting toxicity was observed. There was no grade 4 toxicity, grade 3 hematological toxicity was mild. One patient developed grade 3 acute esophagitis, but was able to complete radiotherapy without delay. Two patients experienced grade 2 late pulmonary toxicity, 1 complete response, 6 partial responses and 1 progressive disease were observed. Conclusions Although the studies stopped too early to assess MTD, we have demonstrated that the combination of cisplatin and pemetrexed with concurrent radiotherapy up to 66 Gy (33 × 2 Gy) is well tolerated and this new combination shows activity in NSCLC. Pemetrexed is the first 3rd generation cytotoxic found to be tolerable at full dose with concurrent radiotherapy.