Phase II trial of ZD0473 as second-line therapy in mesothelioma

Our plain-English summary of Phase II trial of ZD0473 as second-line therapy in mesothelioma, by G. Giaccone, M.E. O'Brien, M.J. Byrne, et al (European Journal of Cancer, 2002).

The study

• Authors: G. Giaccone, M.E. O'Brien, M.J. Byrne, M. Bard, E. Kaukel, B. Smit
• Journal: European Journal of Cancer
• Published: 2002;38 Suppl 8:S19-24
• Cited by: 40 articles, as counted by NIH iCite
• Read it: PubMed · 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 < or = 2. A starting dose of 120 mg/m2 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 > or = 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.

In plain English

This phase II, open-label, multicentre trial had no comparison group. It tested the platinum drug ZD0473 in 47 patients with malignant pleural mesothelioma that had relapsed or progressed after one prior chemotherapy regimen. The study did not examine asbestos exposure. Starting doses were 120 or 150 mg/m2, and patients received a median of 3 cycles. Of 43 patients with assessable tumours, none had a complete or partial response. Five had a minor response, 19 stable disease and 17 disease progression; 2 died before a response could be assigned. In these evaluable patients, median time to progression was 77 days (95% CI 44 to 105) and median time to death was 203 days (95% CI 165 to 277). The main toxicity was low blood platelets (thrombocytopenia), at grade 3 or 4 in 17 of 47 patients. Nausea was the most common non-haematological adverse event, recorded in 28 of 47 patients regardless of cause. No clinically significant kidney, nerve or hearing toxicity was seen. The authors concluded that ZD0473 had manageable tolerability but produced no complete or partial responses, and that second-line mesothelioma trials are feasible.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Phase II, open-label, non-comparative (single-arm), multicentre drug trial
• Who was studied: 47 patients with histologically confirmed malignant pleural mesothelioma that had relapsed or progressed after one prior chemotherapy regimen. All were aged over 18, with a life expectancy over 12 weeks. There were 41 men and 6 women, median age 59 (range 37 to 75). Author affiliations were in the Netherlands, UK, Australia, France, Germany and South Africa. Trial dates are not given.
• Exposure: Not an asbestos exposure study. The treatment studied was the platinum drug ZD0473, given by intravenous infusion. 14 patients started at 120 mg/m2, and 6 of them were later escalated to 150 mg/m2. 33 patients started at 150 mg/m2.
• Main results:
  • 147 treatment cycles were given in total; patients received a median of 3 cycles (range 1 to 6).
  • Of the 43 patients evaluable for tumour response, none had a complete or partial response.
  • Among the 43 evaluable patients, 5 had a minor response and 19 had stable disease. 17 had disease progression, and 2 died before a response could be assigned.
  • Disease control rate (minor response plus stable disease for at least 6 weeks) was 55.8% (95% CI: 39.9%, 70.9%).
  • In evaluable patients, median time to progression was 77 days (95% CI: 44, 105 days). Median time to death was 203 days (95% CI: 165, 277 days).
  • The main toxicity was haematological, most often thrombocytopenia. Grade 3 or 4 thrombocytopenia occurred in 17 of 47 patients (36.2%).
  • Nausea was the most common non-haematological adverse event at all grades, in 28 of 47 patients (59.6%). These events were counted irrespective of causality.
  • No clinically significant kidney (nephro-), nerve (neuro-) or hearing (oto-) toxicity occurred.
  • Five patients withdrew because of adverse events (treatment-related in three), and 29 withdrew because of disease progression.
  • By the time of data cut-off, 35 of the 47 patients had died.
  • Forty patients completed the FACT-L quality-of-life questionnaire. Quality of life changed little, and median scores did not alter significantly.
• The authors' conclusion: The authors concluded that ZD0473 showed a manageable tolerability profile but produced no complete or partial responses as second-line treatment of mesothelioma. They also concluded that clinical trials in second-line mesothelioma patients are feasible.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Second-Line Therapy, Mesothelioma, Pleural Mesothelioma, Chemotherapy, Performance Status, Disease Progression, confidence interval, Clinical Trial.

Related studies

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• A phase II clinical trial of the vascular disrupting agent BNC105P as second line chemotherapy for advanced Malignant Pleural Mesothelioma — A.K. Nowak, C. Brown, et al. (2013)
• Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): a multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial — M. Maio, A. Scherpereel, et al. (2017)
• A phase II study of intermittent sunitinib malate as second-line therapy in progressive malignant pleural mesothelioma — A.K. Nowak, M.J. Millward, et al. (2012)
• Lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma: an international, multi-centre, single-arm, phase II trial (SAKK 17/16) — Y. Metaxas, M. Früh, et al. (2020)
• Phase II trial of carboplatin in the management of malignant mesothelioma — D. Raghavan, P. Gianoutsos, et al. (1990)

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