Pergamoo zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA ~woprmt_‘fo,,md ofCancer Vol. 3OA, No. 8, pp. 1061-1064,1994 cqlyr@~~1994ELgvicrscicnceLtd Rin~cdinGrcatBrimin. AUri&ts~ed 0959-8049l?x57.00+0.00 zyxwv Docetaxel (Taxotere) in Advanced Malignant Melanoma: a Phase II Study of the EORTC Early Clinical Trials Group S. Aamdal, I. Wolff, S. Kaplan, R. Paridaens, J. Kerger, J. Schachter, J. Wanders, H.R. Franklin and J. Verweij The antitumour activity of zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA docetaxel was investigated in patients with advanced malignant melanoma. Docetasel, 100 mg/m*, intravenous, over 60 min, was administered every 3 weeks. Response evaluation was performed after two cycles. No prophylactic treatment with steroids or antihistamines was given. 38 patients were included, 36 were eligible and evaluable for toxicity and 30 patients were evaluable for response. The main haematological toxicity was neutropenia [ 17 patients with common toxicity criteria (CTC) grade 4 and 11 CTC grade 33with nadir after S-8 days and rapid recovery. The most frequent non-haematological toxicity was general&l alopecia (83% of the patients). Asthenia, malaise and fatigue were also seen in 58%. Skin toxicity was also kquent. Hypersensitivity reactions (erythematous rash, u&aria, blood pressure changes and tachycardia), seen in 42% of the patients, were mild to moderate. Oedema was registered in one fifth of the patients and developed after four or more treatment cycles. The overall response rate in the evaluable patients was 17% (five partial responders). We conclude that docetaxel has activity in advanced malignant melanoma. zyxwvutsrqponmlkjihgfedcbaZYXWVUTS EurJ C anc e r, Vol. 30A, No. 8, pp. 1061-1064,1994 INTRODUCTION DOCETAXEL IS a semisynthetic taxoid synthesised from 10 deacet- yl-baccatin III, a compound isolated from the needles of zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFE Tams Baccazu L, the European yew. Docetaxel binds to microtubules, induces tubulin polymerisation and forms extremely stable and non-functional microtubules in the cell [ 11. In preclinical test systems, docetaxel has demonstrated a broad spectrum of antitumour activity against both murine ahd human tumours [l-4]. Compared to paclitaxel, another recently developed taxoid, docetaxel was more active in subcutaneously growing murine B16 malignant melanoma. Docetaxel gave 2.7- times higher log cell kill than paclitaxel with equitoxic doses [ 11. Against a paclitaxel-resistant cell line, docetaxel was found to be a five times more potent inhibitor than paclitaxel[5] and, in two ovarian tumour cell lines, docetaxel was more active than conventional cytostatic agents like cisplatin, cyclophosphamide and doxorubicin [3]. In addition, in freshly explanted clonogenic human tumour cells, docetaxel was more active than paclitaxel and clearly more active than a variety of conventional potent antitumour agents tested in the same tumour cells [3]. In clinical phase I trials, the dose-limiting toxicity has been Correspondence to S. Aamdal at the Dept. of Oncology, Norwegian Radium Hospital, 0310 Oslo, Norway. I. Wolff is at the Medizinische Klinik, Nuremberg, Germany; S. Kaplan is at the Kantonsspittal, Division of Oncology, Base& Switzerland; R. Paridaens is at the Dienst Gezwelziekten UZ St Raphael, Leuven; J. Kerger is at the Institut Jules Bordet, Brussels, Belgium; J. Schachter is at the Beilinson Medical Center, Petach Tikva, Israel; J. Wanders and H.R. Franklin are at 6 EORTC New Drug Development Of&e, Amsterdam, The Netherlands; and J. Verweij is at the Rotterdam Cancer Institute, Rotterdam, The Netherlands. Revised 11 Apr. 1994; accepted 20 Apr. 1994. neutropenia [ 5-91. When the infusion time was shortened from 6 and 24 h to 1 h, oral mucositis, which had been the dose- limiting toxicity in several phase I trials, was significantly reduced [8]. Other toxicities observed were moderate anaemia, skin toxicity, infrequent thrombocytopenia and dose-dependent alopecia. Hypersensitivity reactions were usually mild. Partial responses were observed in heavily pretreated patients with ovarian carcinoma [4, 71, mammary carcinoma [5, 71, small cell [7] and non-small cell lung carcinoma [6]. The present phase II trial was initiated in order to investigate the antitumour activity of docetaxel in advanced malignant melanoma. PATIENTSAND METHODS Eligibility criteria included informed consent, histological or cytological documentation of malignant melanoma, locally advanced, non-resectable or metastatic disease with measurable progressing lesions. Patients with brain or leptomeningeal met- astasis, second malignancies, other serious illnesses, sympto- matic peripheral neuropathy common toxicity criteria (CTC) grade 22, prior or concurrent treatment with colony-stimulating factors or concomitant treatment with prednisone (more than 10 mg/day), were not eligible for inclusion. Other eligibility criteria were age between 18 and 75 years, life expectancy of more than 3 months, performance status (WHO) 5 2, neutrophils 2 2000/~1, platelet count 2 100000/~1 and serum creatinine 5140 ~0l/1.1fserumcreatininewas10%140 ~ol/l,creatinine clearance was measured and the required value for study inch&on was ~60 ml/min. The hepatic enzyme, SGOT (serum glutamic oxaloacetic rransferase), had to be within twice the upper limit of normal (within three times if proven liver metastases) and bilirubin within 1.25 times the upper normal value. zyxwvutsrqponmlkjihgfedcbaZYXW 1061