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

Surmont, V.; Smit, E.F.; de Jonge, M.; Aerts, J.G.; Nackaerts, K.; Vernhout, R.; Gras, J.; Van Wijk, A.; Phernambucq, E.C.J.; van Meerbeeck, J.P.; Senan, S.; Kraaij, C.J.; Chouaki, N.; Praag, J.; van Klaveren, R.J.

doi:10.1016/j.lungcan.2009.12.001

« Previous Next »Lung Cancer
Volume 69, Issue 3 , Pages 302-306, September 2010

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

V. Surmont
- Department of Respiratory Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium
- Corresponding author. Tel.: +32 9 332 1530; fax: +32 9 332 2341.
E.F. Smit
- Department of Pulmonology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands
M. de Jonge
- Department of Medical Oncology, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
J.G. Aerts
- Department of Pulmonology, Amphia Hospital, Breda, The Netherlands
K. Nackaerts
- Department of Pulmonology, University Hospital Gasthuisberg, Leuven, Belgium
R. Vernhout
- Department of Trials and Statistics, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
J. Gras
- Department of Trials and Statistics, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
A. Van Wijk
- Department of Pulmonology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands
E.C.J. Phernambucq
- Department of Pulmonology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands
J.P. van Meerbeeck
- Department of Respiratory Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium
S. Senan
- Department of Radiation Oncology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands
C.J. Kraaij
- Eli Lilly, Houten, The Netherlands
N. Chouaki
- Eli Lilly France, Paris, France
J. Praag
- Department of Radiation Oncology, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
R.J. van Klaveren
- Department of Pulmonology, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands

Received 9 September 2009; received in revised form 1 December 2009; accepted 5 December 2009. published online 25 January 2010.

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 naïve patients received 1 cycle of cisplatin 80mg/m² in study I (stage III NSCLC), 75mg/m² in study II (LD-SCLC) and pemetrexed 500mg/m² before the phase I part. In study I, patients were treated in cohorts with escalating cisplatin doses (60–80mg/m²), pemetrexed doses (400–500mg/m²) and concurrent escalating radiotherapy doses (66Gy in 33–27 fractions). In study II, patients were treated with cisplatin 75mg/m² and escalating pemetrexed doses (400–500mg/m²) with concurrent escalating radiotherapy doses (50–62Gy).

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 66Gy (33×2Gy) 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.

Keywords: Chemo-radiotherapy, Cisplatin, Concurrent, Pemetrexed, Phase I, Toxicity