Oxaliplatin and raltitrexed in the treatment of inoperable malignant pleural mesothelioma: results of a pilot study

Our plain-English summary of Oxaliplatin and raltitrexed in the treatment of inoperable malignant pleural mesothelioma: results of a pilot study, by R. Maisano, N. Caristi, G. Toscano, et al (Tumori, 2001).

The study

• Authors: R. Maisano, N. Caristi, G. Toscano, M. Aragona, P. Spadaro, P. Amadio, M. Mare, M. Zavettieri, F. La Torre
• Journal: Tumori
• Published: 2001;87(6):391-3
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Aims And Background: The treatment of inoperable malignant pleural mesothelioma is a challenge for the oncologist. Available chemotherapy regimens achieve poor results, therefore new agents or combinations are needed. In a phase I study, the combination of oxaliplatin and raltitrexed was shown to be active against malignant pleural mesothelioma. We herein report the results of a pilot study about the treatment of this disease.

Methods: From April 1999 to June 2000, we enrolled 11 chemotherapy-naïve patients with inoperable malignant pleural mesothelioma suitable to receive the following combination chemotherapy: raltitrexed, 3 mg/m2 iv, and oxaliplatin, 130 mg/m2, as a 2-hr infusion every 3 weeks.

Results: Four partial responses, 1 regression of disease (objective response rate, 45%; 95% CI, 15.6-74.4%), 4 stable diseases and 2 progressions of disease were observed. An improvement in disease-related symptoms was recorded in all responders and in 2 patients with stable disease. Toxicity was mild, with no toxic-related death and only 1 episode of grade 4 neurotoxicity.

Conclusions: We consider the combination promising and worthy of further studies.

In plain English

This pilot study from Messina, Italy, tested a two-drug chemotherapy combination, raltitrexed and oxaliplatin, in people with malignant pleural mesothelioma that could not be operated on. Between April 1999 and June 2000, 11 patients who had not had chemotherapy before were enrolled. The patient table listed 7 as asbestos-exposed and 4 as not. Each patient received raltitrexed (3 mg/m2) followed by oxaliplatin (130 mg/m2) every 3 weeks, for 73 cycles in total. Four patients had a partial response and one had regression of disease, an objective response rate of 45% (95% confidence interval 15.6 to 74.4%). Four had stable disease and 2 had progression. The median response lasted 27 weeks. Symptoms improved in all responders and in 2 patients with stable disease, although this was not a planned end point. There were no treatment-related deaths. One patient stopped treatment because of grade 4 nerve toxicity. No grade 3 or 4 blood toxicity was recorded. The authors considered the combination promising. Slow enrollment led them to stop the trial and propose a confirmatory multicenter phase II trial.

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: Pilot study of chemotherapy (the authors also describe it as a phase II study), single treatment group, no comparison group
• Who was studied: 11 patients with inoperable malignant pleural mesothelioma who had not received prior chemotherapy, enrolled April 1999 to June 2000 (authors based in Messina, Italy). Table 1 lists 10 male and 1 female patient, median age 62 (range 32-70), and 10 epithelial and 1 mixed mesothelioma.
• Exposure: Treatment studied: raltitrexed 3 mg/m2 as a 15-minute infusion, followed 45 minutes later by oxaliplatin 130 mg/m2 as a 2-hour infusion, every 3 weeks. The article gives no fiber types or sources of asbestos exposure.
• Main results:
  • Table 1 recorded asbestos exposure as yes for 7 patients and no for 4.
  • 73 chemotherapy cycles were given in total. The median was 5 cycles per patient (range 3-11).
  • Among the 11 patients: 4 partial responses and 1 regression of disease, giving an objective response rate of 45% (95% CI, 15.6-74.4%). There were 4 stable diseases and 2 progressions.
  • Median duration of response was 27 weeks (range 6-52+ weeks). Median time to progression was 16.5 weeks (range 6-52+ weeks).
  • Disease-related symptoms improved in all responders and in 2 patients with stable disease. Clinical benefit was not an end point of the study.
  • There were no treatment-related deaths. Grade 3-4 toxicities were mainly gastrointestinal: 5 episodes (6.8%) of grade 3 diarrhea and 4 episodes (5.5%) of grade 3 transaminase elevation.
  • Three episodes of grade 3 neurotoxicity were observed. Therapy was interrupted in one patient after the 11th course because of grade 4 neurotoxicity, at a cumulative dose of 1430 mg/m2.
  • No grade 3-4 hematologic (blood) toxicity was recorded.
• The authors' conclusion: The authors considered the raltitrexed and oxaliplatin combination promising, in agreement with a French phase II study. They stopped the trial because of slow accrual and proposed a confirmatory multicenter phase II trial.
• Limitations the authors state:
  • The trial was stopped because patients were enrolled slowly.
  • Clinical benefit (symptom improvement) was not a planned end point of the study.

Topics

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

Medical terms in this study, explained in our Lexicon: Raltitrexed, Pleural Mesothelioma, Chemotherapy.

Related studies

• Phase I, dose-finding, and pharmacokinetic study of raltitrexed combined with oxaliplatin in patients with advanced cancer — K. Fizazi, M. Ducreux, et al. (2000)
• Combination raltitrexed (Tomudex(R))-oxaliplatin: a step forward in the struggle against mesothelioma? The Institut Gustave Roussy experience with chemotherapy and chemo-immunotherapy in mesothelioma — K. Fizazi, R. Caliandro, et al. (2000)
• Raltitrexed: current clinical status and future directions — E. Van Cutsem, D. Cunningham, et al. (2002)
• Raltitrexed in mesothelioma — V.F. Surmont, J.P. van Meerbeeck (2011)
• Raltitrexed plus cisplatin is cost-effective compared with pemetrexed plus cisplatin in patients with malignant pleural mesothelioma — B. Woods, N. Paracha, et al. (2012)
• In Australia, patients and government at odds over mesothelioma treatment costs — V. Burkitt (2007)

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