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

Our plain-English summary of 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, by K. Fizazi, R. Caliandro, P. Soulié, et al (European Journal of Cancer, 2000).

The study

• Authors: K. Fizazi, R. Caliandro, P. Soulié, A. Fandi, C. Daniel, A. Bedin, H. Doubre, J. Viala, J. Rodier, L. Trandafir, T. Le Chevalier, E. Cvitkovic, J. Armand, P. Ruffié
• Journal: European Journal of Cancer
• Published: 2000;36(12):1514-21
• Type of article: Meta-analysis
• Cited by: 38 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The aim of this study was to review the experience of the Institut Gustave Roussy in 163 patients with malignant mesothelioma over a 9-year period. Data from seven consecutive prospective trials, four of chemo-immunotherapy and three of chemotherapy were reviewed. The rationale, methods and results of these trials are summarised and discussed. 98 patients were included in four phase II trials of chemo-immunotherapy whose common denominator was a combination of cisplatin and alpha-interferon. The response rate ranged from 15% to 40%. High-dose weekly cisplatin combined with alpha-interferon yielded the highest response rate but the toxicity of this regimen was considered unacceptable. Neither higher doses of alpha-interferon or the addition of mitomycin C or interleukin-2 to the regimen were able to enhance the activity of this combination. 18 patients were included in a paclitaxel-cisplatin phase II trial. The response rate was only 6% (95% confidence interval (CI): 0-24) and toxicity was also significant. This regimen was, therefore, considered ineffective. Of 17 patients with mesothelioma included in a phase I trial that combined raltitrexed and oxaliplatin, 6 (35%) obtained a partial response. Responses were seen even in cisplatin-refractory mesothelioma. Preliminary results of a subsequent ongoing phase II trial using raltitrexed (3 mg/m(2)) and oxaliplatin (130 mg/m(2)) have confirmed this promising activity with a 30% (9/30) response rate (95% CI: 15-49). The tolerance of this outpatient regimen is acceptable (no significant haematological toxicity and no alopecia) and compares favourably with that of our previous regimens. The final results concerning response and survival are required to confirm the efficacy of this combination. The preliminary results of two studies suggest promising activity with the combination of raltitrexed-oxaliplatin in malignant mesothelioma. The efficacy/toxicity ratio of this combination compares favourably with that of our previous chemotherapy and chemo-immunotherapy regimens.

In plain English

The authors reviewed seven consecutive prospective trials at their institution, the Institut Gustave Roussy, France, in 163 patients with malignant mesothelioma, 1991 to 1999. Four trials in 98 patients tested cisplatin plus alpha-interferon chemo-immunotherapy, with response rates of 15% to 40%. High-dose weekly cisplatin with alpha-interferon gave the highest response rate, but its toxicity was considered unacceptable. Higher interferon doses, mitomycin C and interleukin-2 did not improve activity. A paclitaxel-cisplatin trial enrolled 18 patients; 1 of 17 evaluable patients had a partial response (6%, 95% confidence interval 0 to 24%). In a phase I trial of raltitrexed plus oxaliplatin, 6 of 17 mesothelioma patients (35%, 95% confidence interval 13 to 61%) had a partial response, 4 previously treated with cisplatin. A preliminary phase II analysis of the same combination found partial responses in 9 of 30 patients (30%, 95% confidence interval 15 to 49%), and the authors called its tolerance acceptable. The authors concluded that raltitrexed-oxaliplatin looked promising. It was too early to judge response duration, time to progression and survival. Asbestos exposure was tabulated but not analysed.

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: Review of the institution's own seven consecutive prospective trials: four chemo-immunotherapy trials (one phase I-II and three phase II) and three chemotherapy trials (two phase II and one phase I)
• Who was studied: 163 patients with histologically proven malignant mesothelioma of the pleura or peritoneum, treated at the Institut Gustave Roussy, Villejuif, France, from 1991 to 1999
• Exposure: The article studied treatments, not asbestos. The regimens were cisplatin plus alpha-interferon, with higher-dose interferon, mitomycin C or interleukin-2 added in later trials; paclitaxel-cisplatin; and raltitrexed (3 mg/m2) plus oxaliplatin (130 mg/m2). The trial tables list how many patients had asbestos exposure (for example, 17 of 30 in the raltitrexed-oxaliplatin phase II trial). No fiber types are given.
• Main results:
  • In the four chemo-immunotherapy trials (98 patients), response rates ranged from 15% to 40%
  • High-dose weekly cisplatin with alpha-interferon gave the highest response rate, but its toxicity was considered unacceptable
  • Higher doses of alpha-interferon, or adding mitomycin C or interleukin-2, did not improve the activity of the cisplatin plus alpha-interferon combination
  • In the paclitaxel-cisplatin phase II trial, 18 patients entered and there was 1 partial response, a response rate of 6%
  • Evaluable patients for response were 17 in the paclitaxel-cisplatin trial, 17 in the raltitrexed-oxaliplatin phase I trial and 30 in the raltitrexed-oxaliplatin phase II trial
  • Response rates with 95% confidence intervals were 6% (0 to 24%) for paclitaxel-cisplatin, 35% (13 to 61%) for the raltitrexed-oxaliplatin phase I trial, and 30% (15 to 49%) for the raltitrexed-oxaliplatin phase II trial (preliminary results)
  • In the raltitrexed-oxaliplatin phase I trial, 6 of 17 mesothelioma patients (35%) had a partial response, including 4 cisplatin-pretreated patients
  • In the preliminary results of the raltitrexed-oxaliplatin phase II trial, 9 of 30 patients (30%) had a partial response, including 2 pretreated patients
  • The authors described the tolerance of the outpatient raltitrexed-oxaliplatin regimen as acceptable
• The authors' conclusion: The authors concluded that their preliminary results with raltitrexed-oxaliplatin looked promising in mesothelioma, and that final results were needed to confirm whether the combination is truly active
• Limitations the authors state:
  • The results of the phase II raltitrexed-oxaliplatin trial were preliminary, and it was too early to draw conclusions on response duration, time to progression, clinical benefit and survival

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, Mesothelioma, Chemotherapy, Immunotherapy, Malignant Mesothelioma, Cisplatin, Mitomycin C, confidence interval.

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)
• Oxaliplatin and raltitrexed in the treatment of inoperable malignant pleural mesothelioma: results of a pilot study — R. Maisano, N. Caristi, et al. (2001)
• Severe electrolyte disturbances after hyperthermic intraperitoneal chemotherapy: oxaliplatin versus mitomycin C — N.M. Rueth, S.E. Murray, et al. (2011)
• 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)

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