Phase II trial of ZD0473 as second-line therapy in mesothelioma
Date
2002
Authors
Giaccone G.
O'Brien M.E.R.
Byrne M.J.
Bard M.
Kaukel E.
Smit B.
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
A phase II, open-label, non-comparative, multicentre trial of the platinum analogue ZD0473 as second-line therapy for pleural mesothelioma has been completed. The objectives were to evaluate the activity and tolerability of ZD0473 in patients with relapsed or progressive disease who had received one prior chemotherapy regimen. Forty-seven patients were recruited onto the trial, all aged >18 years with a life-expectancy >12 weeks, and World Health Organization (WHO) performance status ≤2. A starting dose of 120 mg/m 2 was administered to 14 patients, six of whom subsequently had their dose escalated to 150 mg/m2. Thirty-three patients received a starting dose of 150 mg/m2. In total, 147 treatment cycles were administered (median number of cycles 3 [range 1-6]). The main toxicity of ZD0473 was haematological (thrombocytopenia) and the most common non-haematological adverse event was nausea. There was no clinically significant nephro-, neuro-, or oto-toxicity. Of the 43 patients evaluable for response, 12% had a minor response (defined by a reduction in lesion size ≥10% but <50%), 44% had stable disease, 40% had disease progression, and two patients died before an objective response could be assigned. Median time to progression and death in evaluable patients was 77 days (95% confidence interval [CI]: 44, 105 days) and 203 days (95% CI: 165, 277 days), respectively. In conclusion, although ZD0473 demonstrated a manageable tolerability profile, no complete or partial responses were seen in second-line treatment of mesothelioma. This trial also demonstrates that clinical trials in second-line mesothelioma patients are feasible. © 2002 Elsevier Science Ltd. All rights reserved.
Description
Keywords
alkaloid, amminedichloro(2 methylpyridine)platinum, antiemetic agent, cisplatin, doxorubicin, gemcitabine, ifosfamide, methotrexate, mitomycin C, navelbine, platinum derivative, vinblastine, amminedichloro(2 methylpyridine)platinum(II), amminedichloro(2-methylpyridine)platinum(II), antineoplastic agent, platinum complex, adult, aged, anemia, anorexia, article, cancer growth, cancer relapse, chemotherapy, clinical article, clinical protocol, clinical trial, constipation, controlled clinical trial, controlled study, death, dose response, drug activity, drug efficacy, drug tolerability, dyspnea, female, human, leukopenia, life expectancy, malaise, male, multicenter study, nausea, nephrotoxicity, neurotoxicity, neutropenia, open study, ototoxicity, pain, phase 2 clinical trial, pleura mesothelioma, priority journal, thorax pain, thrombocytopenia, vomiting, world health organization, chemically induced disorder, hematologic disease, intravenous drug administration, mesothelioma, middle aged, pleura tumor, treatment outcome, Adult, Aged, Antineoplastic Agents, Dose-Response Relationship, Drug, Dyspnea, Female, Hematologic Diseases, Humans, Infusions, Intravenous, Male, Mesothelioma, Middle Aged, Organoplatinum Compounds, Pleural Neoplasms, Treatment Outcome
Citation
European Journal of Cancer
38
SUPPL. 8
38
SUPPL. 8