Lung Cancer 34 (2001) 125–131 Phase I trial of weekly docetaxel combined with cisplatin in patients with non-small cell lung cancer Tomonobu Koizumi *, Toshiyuki Tsunoda, Keisaku Fujimoto, Hiroshi Nomura, Kazuya Hirai, Shigeru Koyama, Kazuyoshi Okada, Keishi Kubo First Department of Internal Medicine, Shinshu Uniersity School of Medicine, 3 -1 -1 Asahi Matsumoto, Shinshu 390 -8621, Japan Received 19 October 2000; received in revised form 9 March 2001; accepted 15 March 2001 Abstract The phase I study was conducted to evaluate the maximum tolerated dose (MTD) and toxicity of weekly administered docetaxel combined with cisplatin in patients with non-small-cell lung cancer (NSCLC). In a dose escalation study, 22 patients, under 75 years old, with unresectable and metastatic untreated NSCLC with performance status (0 – 1) were enrolled. Patients were treated with cisplatin (day 1) and weekly docetaxel (days 1, 8, 15). Dose escalation levels in mg/m 2 were for cisplatin and docetaxel; 70 and 15 (level 1), 80 and 15 (level 2), 80 and 20 (level 3), 80 and 25 (level 4), 80 and 30 (level 5), respectively. Chemotherapy was repeated for at least two cycles every 28 days. All patients were assessable for toxicities. Although grade 3 neutropenia occurred in one case in level 4, there were no significant modifications of chemotherapy schedule until level 4. Grade 3 neutropenia occurred in all cases receiving level 5. One patient developed an infection, and two had incomplete recovery of neutropenia by the 28th day after the first cycle of chemotherapy. Nonhematological toxicities, including nephrotoxicity, nausea/vomit- ing, alopecia and hypersensitivity reaction, were tolerable. However, one case developed severe hyponatremia. Among 21 patients evaluable for response, eight cases achieved partial response, thus the overall response was 39%. Weekly administration of docetaxel at 25 mg/m 2 (days 1, 8, 15) combined with cisplatin 80 mg/m 2 (day 1) is recommended for phase II studies. The responses observed in the present study suggest an identical high degree of activity against NSCLC with less hematotoxicities compared with a standard schedule of cisplatin and docetaxel. © 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Weekly docetaxel; Cisplatin; Non-small-cell lung cancer; Neutropenia www.elsevier.nl/locate/lungcan 1. Introduction Docetaxel (Taxotere) is a semisynthetic taxoid that possesses significant activity in the treatment of patients with non-small-cell lung cancer (NSCLC) [1 – 4]. Docetaxel increases the rate of microtubules assembly and inhibits the depoly- * Corresponding author. Tel.: +81-263-372631; fax: +81- 263-363722. E-mail address: tomonobu@hsp.md.shinshu-u.ac.jp (T. Koizumi). 0169-5002/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved. PII:S0169-5002(01)00229-X