When we come to considering 4th line, therapy, there are few studies, guideline statements and no prospective randomized trials, because this is a small group of patients. For example, NCCN has recomendations for 1st, 2nd and 3rd line but not for the 4th line.
In such situtions, randomized trials, if there are any, are important in guiding the decision making. A randomized phase II study was presented in 2002. While not specifically in fourth line, two chemotherapy arms were evaluated in this randomized phase II trial: Arm 1(gemcitabine/irinotecan 1000 mg/m2/100 mg/m2]) and arm 2 (gemcitabine/docetaxel 1000 mg/m2/40 mg/m2). Both doublets were tolerable as first line therapy for good PS pts with advanced NSCLC. Response Rates were disappointing in both arms but there were some long term survivors in the gemcitabine/ irinotecan arm. In second-line the results were decent in another randomized study of gemcitabine/ irinotecan with or without celecoxib.
Another study looked at a previously treated group, more like our patient, but with small cell cancer, the regimen was active and tolerable.
The deciding evidence for me is the randomized study of gemcitabine/ irinotecan versus irinotecan alone in 2nd line. No significant differences between the two groups in terms of the median duration of response, time to tumour progression, overall survival and 1-year survival were observed. The CPT-11/gemcitabine regimen significantly improved the patients’ quality of life (‘general mood today’ (P=0.014), ‘coughing’ (P=0.003) and ‘intensity of symptoms’ (P=0.034)) compared with CPT-11.
Thus there is evidence supporting use of the combination is previously treated patients. I consider it sufficient under the plan to express experts’ opinion that the therapy is standard and no farther studies are being planned as far as I know.
Caio Max S Rocha Lima, Naiyer A Rizvi, Karen Zhang, James E Herndon, Jeffrey Crawford, Gerald W King, Mark R Green CALGB 39809: Randomized phase II trial of gemcitabine/irinotecan and gemcitabine/docetaxel in stage IIIB (malignant pleural effusion) or stage IV NSCLC bstract No: 1344 Proc Am Soc Clin Oncol 21: 2002 (abstr 1344).
M. Nishio, F. Ohyanagi, A. Horikike, Y. Okano, Y. Satoh, O. Sakae, Y. Ishikawa, K. Nakagawa, K. Nakagawa, T. Horai Phase II trial of gemcitabine and irinotecan in previously treated patients with small-cell lung cancer. Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 7718
Rogerio Lilenbaum, Mark A. Socinski, Nasser K. Altorki, Lowell L. Hart, Roger S. Keresztes, Subramanian Hariharan, Mark E. Morrison, Rana Fayyad, Phillip Bonomi Randomized Phase II Trial of Docetaxel/Irinotecan and Gemcitabine/Irinotecan With or Without Celecoxib in the Second-Line Treatment of Non–Small-Cell Lung Cancer
Journal of Clinical Oncology, Vol 24, No 30 (October 20), 2006: pp. 4825-4832
V Georgoulias et al, Irinotecan plus gemcitabine vs irinotecan for the second-line treatment of patients with advanced non-small-cell lung cancer pretreated with docetaxel and cisplatin: a multicentre, randomised, phase II study British Journal of Cancer (2004) 91, 482-488.