Summary
Docetaxel has shown remarkable radiosensitizing in vitro properties. In a previous phase I/II dose escalation study in non- small-cell lung cancer (NSCLC) we observed a high response rate after concomitant boost radiotherapy and weekly docetaxel. The maximum tolerated dose was 30 mg m–2 week–1. In the present phase II study we evaluated whether weekly docetaxel and conventionally fractionated radiotherapy could be better tolerated and equally effective in the treatment of locally advanced NSCLC. Thirty-five patients with T3, T4/N2, T3/M0-staged disease were recruited. Docetaxel (30 mg m–2) was given as a 30 min infusion once a week. Asthenia and radiation-induced oesophagitis were the main side-effects of the regimen enforcing 2-week treatment delay in 6/35 (17%) patients and minor delay (3–7 days) in another 11/35 (31%) patients. Neutrophil, platelet and haemoglobin toxicity was minimal, but pronounced lymphocytopenia was observed. Complete response (CR) of the chest disease was observed in 12/35 (34%) patients and partial response in 16/35 (46%). Although not statistically significant (P = 0.19), a higher CR rate (8/18; 44%) was observed in patients who accomplished their therapy within the scheduled treatment time (44–47 days) as compared to patients that interrupted their treatment for several days due to treatment-related toxicity (CR 4/17; 23%). The overall survival and the local progression-free survival at 1 year was 48% and 60% respectively. We conclude that docetaxel combination with radiotherapy is a promising approach for the management of locally advanced NSCLC that results in high CR rate. Further trials with docetaxel-based radiochemotherapy should integrate accelerated radiotherapy together with cytoprotection.
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References
Beham, M., Vogel, M., McDonnell, J., Farkas, S. t., Furst, A. & Jauch, K. W. (1998). Apoptosis after genotoxic damage is enhanced by Taxol-induced phosphorylation of bcl-2 and correlates with nuclear import of p53. Proc Am Assoc Cancer Res 39: 463 (abstract no. 3151)
Brodin, O., Nou, E., Mercke, C., Lindén, C. J., Lundström, R., Arwidi, A., Brink, J. & Ringborg, U. (1996). Comparison of induction chemotherapy before radiotherapy with radiotherapy only in patients with locally advanced squamous cell carcinoma of the lung. The Swedish Lung Cancer Study Group. Eur J Cancer 32A: 1893–1900.
Cerny, T., Kaplan, S., Pavlidis, N., Schöffski, P., Epelbaum, R., van Meerbeek, J., Wanders, J., Franklin, H. R. & Kaye, S. (1994). Docetaxel (taxotere @) is active in non-small cell lung cancer: a phase II trial of EORTC Early Clinical Trials Group (ECTG). Br J Cancer 70: 384–387.
Chaffey, J. T. & Hellman, S. (1971). Differing responses to radiation of murin bone marrow stem cells in relation to the cell cycle. Cancer Res 31: 1513–1516.
Choy, H., Rodriguez, F., Koester, S., Hilsenbeck, S. & Von Hoff, D. D. (1992). Synergistic effects of Taxol/Taxotere on radiation sensitivity on human tumor cell. Int J Radiat Oncol Biol Phys 24: 274–275 (abstract no. 1059).
Dillman, R. O., Seagren, S. L., Propert, K. J., Guerra, J., Eaton, W. L., Perry, M. C., Carey, R. W., Frei, EF III & Green, M. R. (1990). A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer. N Engl J Med 323: 14940–14945.
Fossella, F. V., Lee, J. S., Murphy, W. K., Lipman, S. M., Calayag, M., Pang, A., Chasen, M., Shin, D. M., Glisson, B., Benner, S., Huber, M., Perez-Soler, R., Hong, W. K. & Rober, M. (1994). Phase II study of docetaxel for recurrent or metastatic non-small cell lung cancer. J Clin Oncol 12: 1238–1244.
Francis, P., Schneider, J., Hann, L., Bolmeceda, C., Barakat, R., Phillips, M. & Hakes, T. (1994). Phase II trial of docetaxel in patients with platinum-refractory advanced ovarian cancer. J Clin Oncol 12: 2301–2308.
Geuritte-Voegelein, F., Guenard, D., Lavelle, F., Le Goff, M., Mangatal, L. & Pottier, P. (1996). Relationships between the structure of Taxol analogues and their antimitotic activity. J Med Chem 34: 992–998.
Haldar, S., Chintapalli, J. & Croce, C. M. (1996). Taxol induces bcl-2 phosphorylation and death of prostate cancer cells. Cancer Res 56: 1253–1255.
Hermanek, P. & Sobin, J. (1992). UICC TNM Classification of Malignant Tumours, 4th ed. Springer-Verlag: Berlin
Koukourakis, M. (1998). The use of ethyol in chemotherapy and radiation therapy. In Cytoprotection in Cancer Therapy: Improving the Therapeutic Index of Cancer Treatment. Ethyol Investigators Meeting, May 1998, Los Angeles, California, USA
Koukourakis, M., Skarlatos, J., Kosma, L., Giatromanolaki, A. & Yannakakis, D. (1995). Radiotherapy alone for non-small cell lung carcinoma. Five year disease-free survival and patterns of failure. Acta Oncol 34: 525–530.
Koukourakis, M., Hlouverakis, G., Kosma, L., Skarlatos, J., Damilakis, J., Giatromanolaki, A. & Yonnakakis, D. (1996). The impact of overall treatment time on the results of radiotherapy for non-small cell lung cancer. Int J Radiat Oncol Biol Phys 34: 315–322.
Koukourakis, M., Kourousis, C., Kamilaki, M., Koukouraki, S., Giatromanolaki, A., Kakolyris, S., Kotsakis, A., Androulakis, N., Bahlitzanakis, N. & Georgoulias, V. (1998). Weekly Docetaxel and Concomitant Boost Radiotherapy for Non-Small-Cell Lung Cancer. A Phase I/II Dose Escalation Trial. Eur J Cancer 34: 838–844.
Koukourakis, M., Stefanaki, E., Giatromanolaki, A., Armenaki, A., Fragiadaki, C., Georgoulias, V., Koumandakis, E., Kranidis, A. & Helidonis, E. (1998). Fractionated carboplatin radiosensitization. A phase I dose escalation study. Am J Clin Oncol 1999 (in press)
Le Chevalier, T., Arriagada, R., Tarayre, M., Lacombe-Terrier, M. J., Laplanche, A., Quoix, E., Ruffie, P., Martin, M. & Douillard, J. Y. (1992). Significant effect of adjuvant chemotherapy on survival in locally advanced non-small-cell lung carcinoma. J Natl Cancer Inst 84: 58
Mattson, K., Holsti, L. R., Holsti, P., Jakobsson, M., Kajanti, M., Liippo, K., Mäntylä, M., Niitamo-Korhonen, S., Nikkanen, V. & Nordman, E. (1998). Inoperable non-small cell lung cancer: radiation with or without chemotherapy. Eur J Cancer Clin Oncol 24: 477–482.
Mauers, A. M., Masters, G., Haraf, D., Hoffman, P. C., Watson, S. M., Golomb, H. M. & Vokes, E. E. (1998). Phase I study of docetaxel with concommitant thoracic radiotherapy. J Clin Oncol 16: 159–164.
Morton, R. F., Jett, J. R., McGinnis, W. L., Earle, J. D., Therneau, T. M., Krook, J. E., Elliott, T. E., Mailliard, J. A., Nelimark, R. A. & Maksymiuk, A. W. et al (1991). Thoracic radiation therapy alone compared with combined chemoradiotherapy for locally unresectable non-small cell lung cancer. A randomized, phase III trial. Ann Intern Med 115: 681–686.
Ringel, I. & Horwitz, S. B. (1991). Studies with RP-56976 (Taxotere): a semi-synthetic analogue of Taxol. J Natl Cancer Inst 83: 288–291.
Shaake-Koning, C., van-den-Bogaert, W., Dalesio, O., Festen, J., Hoogenhout, J., van Houtte, P., Kirkpatrick, A., Koolen, M., Maat, B. & Nijs, A. (1992). Effects of concomitant cisplatin and radiotherapy on inoperable non-small cell lung cancer. N Engl J Med 326: 524–530.
Throuvalas, N., Antonadou, D., Pulizzi, M. & Sarris, G. (1995). Evaluation of the efficacy and safety of GM-CSF in the prophylaxis of mucositis in patients with head and neck cancer treated by RT. In Proceedings of ECCO 1995, pp. 593. Federation of European Cancer Societies: Paris (abstract 431)
Tomiak, E., Piccart, M. J., Kerger, S., Lips, S., Awada, A., de Valeriola, D., Lossignol, D., Sculier, J. P., Auzannet, V., Le Bail, N., Bayssas, M. & Klastersky, J. (1994). Phase I study of docetaxel administered as 1-hour intravenous infusion on a weekly basis. J Clin Oncol 12: 1458–1467.
World Health Organization (1979). Handbook for Reporting Results of Cancer Treatment. WHO Offset Publications: Geneva
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Koukourakis, M., Bahlitzanakis, N., Froudarakis, M. et al. Concurrent conventionally factionated radiotherapy and weekly docetaxel in the treatment of stage IIIb non-small-cell lung carcinoma. Br J Cancer 80, 1792–1796 (1999). https://doi.org/10.1038/sj.bjc.6690599
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DOI: https://doi.org/10.1038/sj.bjc.6690599
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